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pubmed_570_19648
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It is well known that the vestibulo-ocular reflex (VOR) is conjugate when measured in the dark with minimal vergence. But the neural basis of the VOR conjugacy remains to be identified. In the present study, we measured the VOR conjugacy during single labyrinth stimulation to examine whether the VOR conjugacy depends on reciprocal stimulation of the two labyrinths. There are conflicting views on this issue. First, since the vestibular signals carried by the ascending tract of Deiters' are distributed exclusively to the motoneurons of the ipsilateral eye, the neural innervations after single labyrinth stimulation are not symmetrical for the two eyes. Thus, single labyrinth stimulation may generate disjunctive VOR responses. Second, the only published study on this issue was an electrooculography (EOG) study that reported disjunctive VOR responses during unilateral caloric irrigation (Wolfe in Ann Otol 88:79-85, 1979). Third, the VOR during unilateral caloric stimulation performed in clinical vestibular tests is routinely perceived to be conjugate. To resolve these conflicting views, the present study examined the VOR conjugacy during single labyrinth stimulation by recording binocular eye position signals in awake monkeys with a search coil technique. In contradiction to the previous EOG study and the prediction based on the asymmetry of the unilateral brainstem VOR circuits, we found that the VOR during unilateral caloric irrigation was conjugate over a wide range of conditions. We conclude that the net neural innervations received by the two eyes are symmetrical after single labyrinth stimulation, despite the apparent asymmetry in the unilateral VOR pathways. A novel role for the ascending tract of Deiters' in the VOR conjugacy is proposed.
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10.1007/s00221-010-2403-3
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pubmed_796_5657
|
Two variants of coxsackievirus group B, type 3 (CVB3) differ in ability to induce myocarditis in Balb/cCUM mice. Infection with the highly pathogenic variant (CVB3M) stimulates autoimmunity to normal cardiocyte antigens, and tissue injury results primarily from an autoreactive cytolytic T lymphocyte (ACTL). Animals infected with the less pathogenic CVB3o variant do not develop ACTL, although CVB3o replicates to high titers in the heart and polyclonal neutralizing antisera fail to distinguish between the two variant virions. The present study uses two IgM mAb derived by fusing spleen cells from CVB3M-infected mice with NS-1 cells. These mAb investigate important differences between the virus variants that may explain why only selected infections trigger autoimmunity. mAb 8A6 is a virus-neutralizing antibody that prevents infection of HeLa cells and cultured cardiocytes by attaching to the virus. mAb 10A1 also interferes with infection but presumably reacts to the virus receptor on the susceptible cells and shows little or no binding to the virions. While 8A6 is equally effective in neutralizing both CVB3o and CVB3M, suggesting that antigenic epitopes on both variants are either identical or highly cross-reactive, 10A1 distinguishes between the variants, suggesting that the pathogenic and less pathogenic viruses use distinct cell surface receptors. Competitive binding studies using radiolabeled CVB3M and either of the unlabeled variants confirm this hypothesis. Both mAb effectively prevent CVB3M-induced cardiac damage in vivo. mAb 10A1 also inhibits autoreactive ACTL lysis of cardiocytes, indicating that the autoimmune effectors may recognize the virus receptor, and that the receptor utilized by a virus may prove important in triggering auto-sensitization.
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pubmed_796_5657
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pubmed_200_12782
|
Pharmacotherapy-induced ototoxicity is growing, especially in developing countries such as South Africa. This highlights the importance of ototoxicity monitoring and management of hearing loss. This article focuses on the establishment of an ototoxicity clinic as a site for the implementation of a service-learning module in the Audiology programme. The clinic offers a unique opportunity of collaboration between pharmacists and an audiologist where pharmacotherapy-induced ototoxicity is uniquely monitored. The Sefako Makgatho Health Sciences University (SMU) provides training to both the disciplines, audiology and pharmacy. The main aim of this article is to describe how ototoxicity monitoring is implemented in the curriculum within such an academic service-learning approach. Through service learning students develop a deeper understanding of course content, acquire new knowledge and engage in civic activity. It simultaneously provides a unique opportunity for interdisciplinary collaboration between the disciplines of audiology and pharmacy. The objectives for this programme are therefore to facilitate learning and to provide a service to the local community by identifying, preventing and monitoring medicine-induced hearing loss in in-hospital and out-patients; as well as to establish inter-disciplinary collaboration between the disciplines and stakeholders for more effective service delivery. The constant interdisciplinary teamwork between the audiologist, pharmacist, physician and nursing staff in the wards results in best practice and management of patients with ototoxic damage.
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10.4102/sajcd.v62i1.96
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pubmed_439_44
|
Background
Numerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD.
Methods
The data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature. Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD.
Results
Overall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment.
Conclusions
The key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.
|
10.21037/jtd-22-86
|
pubmed_898_9207
|
We present a technological advancement for the estimation of the affinities of Protein-Protein Interactions (PPIs) in living cells. A novel set of vectors is introduced that enables a quantitative yeast two-hybrid system based on fluorescent fusion proteins. The vectors allow simultaneous quantification of the reaction partners (Bait and Prey) and the reporter at the single-cell level by flow cytometry. We validate the applicability of this system on a small but diverse set of PPIs (eleven protein families from six organisms) with different affinities; the dissociation constants range from 117 pm to 17 μm After only two hours of reaction, expression of the reporter can be detected even for the weakest PPI. Through a simple gating analysis, it is possible to select only cells with identical expression levels of the reaction partners. As a result of this standardization of expression levels, the mean reporter levels directly reflect the affinities of the studied PPIs. With a set of PPIs with known affinities, it is straightforward to construct an affinity ladder that permits rapid classification of PPIs with thus far unknown affinities. Conventional software can be used for this analysis. To permit automated analysis, we provide a graphical user interface for the Python-based FlowCytometryTools package.
|
10.1074/mcp.TIR119.001692
|
pubmed_625_20606
|
The strong selection in search for a higher growth rate in broilers has resulted in adverse effects such as metabolic disorders, low responsiveness of the immune system, and decreased resistance to pathogens. On the other hand, newly hatched chicks rely mostly on innate immune responses until their gut gets colonized with microbiota. In consequence, early access to active substances or bacteria (pre- and post-hatch) is particularly relevant here because in broilers much of the immune system development occurs early in life. Therefore, early stimulation of beneficial microflora is critical, as it affects, to a great extent, the entire life-span of an individual, and also because the nutritional manipulations of the gastrointestinal tract (GIT) microbiome to enhance productivity and health are rather limited by the resilience of the ecosystem once established in the chicken´s gut. Early life or developmental programming is based on the assumption that the development of diseases later in life can be modulated by perturbations or environmental exposures during critical pre- or early post-natal life. Substances such as plant derivatives, Na butyrate, pre- and probiotics, and β-glucans have been shown to induce beneficial microbiological and immunological changes within the GIT, and therefore are potential candidates to be used as tools to manipulate GIT functionality in the young chicken. Accordingly, substances as these might represent promising candidates to study intestinal microbiota/immune system modulation in broilers´ early stages of breeding. In ovo-delivered prebiotics and synbiotics have been shown to have no adverse effect on the development of the immune system in exposed chickens, while being able to affect lymphoid-organs' morphology in chickens. In ovo procedures have also been proposed as means of promoting a healthy microflora in embryonic guts and stimulating maturation of the cellular and humoral immune responses in central and peripheral immune organs, including those in the GIT. The purpose of this presentation is to discuss the potential usefulness of the instruments currently available to induce early life programming in broilers.
|
10.3382/ps/pey416
|
pubmed_906_16327
|
Magnolol has been reported to have anticancer activity. In this study we found that treatment with 100 microm magnolol induced apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines but not in human untransformed gingival fibroblasts and human umbilical vein endothelial cells. Our investigation of apoptosis in Hep G2 cells showed a sequence of associated intracellular events that included (a) increased cytosolic free Ca(2+); (b) increased translocation of cytochrome c (Cyto c) from mitochondria to cytosol; (c) activation of caspase 3, caspase 8, and caspase 9; and (d) downregulation of bcl-2 protein. Pretreatment of the cells with the phospholipase C inhibitor 1-[6-[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) or the intracellular chelator of Ca(2+) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM) inhibited the subsequent magnolol augmentation of [Ca(2+)](i) and also the activation of caspase-8 and caspase-9, so that the occurrence of apoptosis in those cells was greatly reduced. Pretreatment of the cells with ZB4 (which disrupts the Fas response mechanism) also decreased the subsequent magnolol-induced caspase-8 activation and reduced the occurrence of apoptosis. We interpreted these findings to indicate that the above-listed sequence of intracellular events led to the apoptosis seen in Hep G2 cells and that [Ca(2+)](i), Cyto c, and Fas function as intracellular signals to coordinate those events.
|
10.1002/mc.1066
|
pubmed_973_13895
|
Poststreptococcal sequelae, especially acute rheumatic fever/rheumatic heart disease continues to occur in significant proportions in many parts of the world, especially in less developed countries. An important factor in the study of rheumatic heart disease is the human genetic susceptibility to the disease. The aim of the present study was to detect the most prevalent HLA class I and class II types associated with risk of rheumatic heart disease in Egyptian children. Our study was performed on 100 patients with rheumatic valvular heart diseases and 71 control subjects. Patients were recruited from the Heart Institute, Embaba, Egypt. HLA typing for HLA class I was performed by serotyping and HLDR allele genotyping was performed using INNO-LiPA kits. In the study of HLA class I, there was a statistically significant increase in the B5 allele (P = 0.03; odds ratio, 3.46 [1.12-10.72]) in patients compared to controls, while B49 and B52 alleles (P = 0.004 and P = 0.02) were found in controls only. There was a statistically significant increase in HLA DR* 04-02, 3.46 (1.12-10.72) and HLA DR *10-0101 5.75 (1.27-25.98) in patients. Meanwhile HLA DR*1309120 was found only in controls (P = 0.02). Our study provides further information on the genetic predisposition for rheumatic valvular disease and the protective genotypes in rheumatic heart disease. Further insight into the molecular mechanisms of the disease will be a useful tool for predicting clinical outcome in those patients and, thus, potentially offer new means and approaches to treatment and prophylaxis, including a potential vaccine.
|
10.1007/s00246-010-9663-3
|
pubmed_71_2803
|
We report an amidine-based small molecule two-photon fluorescent probe (ELP1) for monitoring vesicle transport from the ER to lysosome in live cells. Two-photon microscopy imaging studies indicated that this probe initially localized in the ER and subsequently transferred to lysosomal compartments through vesicular transport. These results may provide an effective tool for studying trafficking-related biology and pathology in real-time.
|
10.1039/c7cc01518f
|
pubmed_320_5589
|
The dentate gyrus is one of the small number of forebrain areas that have continued adult neurogenesis. During development the dentate gyrus acquires the capacity for neurogenesis by generating a new neurogenic stem cell niche at the border between the hilus and dentate granule cell layer. This is in distinction to the other prominent zone of continued neurogenesis in the subventricular zone where neurons are born in a structure directly descended from the mid-gestation subventricular zone. The ability to generate this newly formed dentate neurogenic niche is controlled by the action of a number of genes during prenatal and early postnatal development that regulate the fate, survival, migration, expansion, and differentiation of the cellular components of the dentate neurogenic niche. In this review, we provide an updated framework discussing the molecular steps and genes involved in these early stages of dentate gyrus formation. We previously described a molecular framework for dentate gyrus morphogenesis that can be associated with specific gene defects (Li, G., Pleasure, S.J. (2005). Dev. Neurosci., 27, 93-99), and here we add additional recently described molecular players and discuss this framework.
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10.1016/S0079-6123(07)63008-8
|
pubmed_788_8886
|
The anticipated therapeutic uses of neural stem cells depend on their ability to retain a certain level of developmental plasticity. In particular, cells must respond to developmental manipulations designed to specify precise neural fates. Studies in vivo and in vitro have shown that the developmental potential of neural progenitor cells changes and becomes progressively restricted with time. For in vitro cultured neural progenitors, it is those derived from embryonic stem cells that exhibit the greatest developmental potential. It is clear that both extrinsic and intrinsic mechanisms determine the developmental potential of neural progenitors and that epigenetic, or chromatin structural, changes regulate and coordinate hierarchical changes in fate-determining gene expression. Here, we review the temporal changes in developmental plasticity of neural progenitor cells and discuss the epigenetic mechanisms that underpin these changes. We propose that understanding the processes of epigenetic programming within the neural lineage is likely to lead to the development of more rationale strategies for cell reprogramming that may be used to expand the developmental potential of otherwise restricted progenitor populations.
|
10.1098/rstb.2006.2010
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pubmed_101_5553
|
The interest in using natural coagulants for wastewater treatment has increased in recent years due to the environmental and health problems associated with the use of traditional coagulants. In this study, starch-based coagulants were tested to treat reject water produced by the dewatering of mesophilic digester sludge at the Viikinmäki wastewater treatment plant (WWTP) in Finland. The goal of this treatment is to prepare the stream for the nitrogen recovery process with membrane contactor technology. Screening tests showed that PrimePHASE 3545 was the best coagulant, and the effective dosage and pH ranges were 10-20 ml/l of the 25% diluted starch and 8-10 pH values, respectively. The process was optimized using Response Surface Methodology (RSM). The best dosage and pH combination generated by RSM was 14.1 ml/l and 9.1, respectively. In these conditions, TN, TP, TOC, SS and VSS removal percentages were 18 ± 0.57%, 80 ± 0.99%, 28 ± 1.19%, 90 ± 3.37%, and 89 ± 2.35%, respectively. However, NH3-N concentration increased by 20 ± 1.7%, mainly due to pH increase. These results held true when tested on a pilot scale at Viikinmäki WWTP in a continuous process. The sludge produced with natural coagulant was found to be of a better quality compared to that of conventional coagulants.
|
10.1016/j.jenvman.2021.112021
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pubmed_415_1514
|
OBJECTIVE
To describe medication use among older community-dwelling Icelanders by collecting information on number of medicine, polypharmacy (>5 medications), and medications by ATC categories. Moreover, to explore the relationship between medication use and various influential factors emphasizing residency in urban and rural areas.
MATERIAL AND METHODS
Population-based, cross-sectional study. Participants were randomly selected from the National registry in one urban (n=118) and two rural (n=68) areas.
INCLUSION CRITERIA
1) ≥ 65 years old, 2) community-dwelling, 3) able to communicate verbally. Information on medication use was obtained from each person's medication list and interviews. A questionnaire and five standardized instruments were used to assess the potential influencing factors.
RESULTS
On average, participants used 3.9 medications and prevalence of polypharmacy was 41%. Men used 3.5 medications on average and women 4.4 (p=0.018). Compared to rural residents, urban residents had fewer medical diagnoses, better mobility, less pain, and fewer depressive symptoms. By controlling for the effects of these variables, more medications were associated with urban living (p<0.001) and more medical diagnoses (p<0.001). Likewise, adjusted odds for polypharmacy increased with urban residency (p=0.023) and more medical diagnoses (p=0.005). Urban residency, more medical diagnoses, higher age, and male gender were related to use of drugs for blood and blood forming organs.
CONCLUSION
The results reveal an unexplained regional difference in medications use by older Icelanders. Further studies are required on why urban residents use at least equal amount of medications as rural residents despite better scores on health assessments.
|
10.17992/lbl.2011.12.401
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pubmed_538_315
|
A new multileaf collimator (MLC) model has been incorporated into version 7.4 of the Pinnacle radiotherapy treatment planning system (Philips Radiation Oncology Systems, Milpitas, CA). The MLC model allows for rounded MLC leaf-ends and provides separate parameters for inter-leaf transmission, intra-leaf transmission and the tongue width of the MLC leaf. In this report we detail the method followed to commission the MLC model for a Varian 120-leaf Millennium MLC (Varian Medical Systems, Palo Alto, CA, USA) for both 6 and 10 MV photons, and test the validity of the model for an IMRT field. Dose profiles in water were measured for a range of square MLC field sizes and compared to the Pinnacle computed dose profiles; in addition, the dose distribution for a series of adjacent MLC fields was measured to observe the model's behaviour along match-lines. Based on these results intra-leaf transmissions of 1.5% for 6 MV and 1.8% for 10 MV, leaf-tip radius of 12.0 cm, an inter-leaf transmission of 0.5%, and a tongue width of 0.1 cm were chosen. Using these values to compute the planar dose distribution for a 6 MV IMRT field, the new version of Pinnacle displayed improved dosimetric agreement with the dose-to-water EPID image and ion chamber measurements when compared to the old version of Pinnacle, particularly along the MLC tongue edge and across match-lines. Discrepancies of up to 5% were observed between calculated and measured doses along match-lines for both 6 MV and 10 MV photons; however, the new MLC model did predict the presence of match-lines and was a significant improvement on the previous model.
|
10.1088/0031-9155/51/4/N03
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pubmed_940_11136
|
Interpersonal communication is largely dependent on interpretation of facial expression and emotion. Difficulties in face processing, and more specifically in gaze discrimination, have been described in schizophrenic patients. According to Baron-Cohen (Mindblindness. M.I.T. Press, Cambridge, MA, 1995), gaze discrimination relies on the functioning of a specific cognitive module, the Eye Direction Detector (EDD). It has been proposed [Rosse et al. (1994) Gaze discrimination in patients with schizophrenia: preliminary report. American Journal of Psychiatry 151, 919-921] that an impairment in gaze discrimination is present in schizophrenia, and plays a fundamental role in inducing the paranoid symptoms reported by many patients. However, in the previous studies, gaze direction detection and interpretation of gaze have never been completely dissociated. The present experiment attempts to test the schizophrenics' skill in a simple gaze direction detection task. A series of photographic portraits of models looking at different directions have been presented to 22 schizophrenic patients and 36 control subjects. For each portrait subjects were asked to determine whether gaze was directed to the right or to the left by pressing a keyboard key. A forced choice paradigm was used. No differences were reported between schizophrenic patients and control subjects. That is, in the present paradigm, schizophrenic patients did not show any specific impairment in detecting the direction of gaze of the portraits. The results are discussed according to the notion that a dissociation is present in schizophrenia between implicit and explicit processes. The present case illustrates how the more automatic elementary functions, such as the detection of gaze direction, may be spared in schizophrenic patients, whereas explicit cognitive functions are likely more affected.
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10.1016/s0165-1781(98)00082-1
|
pubmed_465_3486
|
Thirteen diabetic women were treated with human insulin of recombinant DNA origin from early pregnancy. One patient previously treated with conventional beef insulin showed a steady fall in insulin antibody levels whilst those previously treated with purified porcine insulin or human insulin showed no changes in species-specific insulin binding or in antibody-bound insulin. Two women with gestational diabetes, who received insulin for the first time during pregnancy, developed insulin antibodies which declined when therapy was withdrawn in the post-partum phase. Insulin antibody was detectable in the foetal circulation in all pregnancies at parturition but did not seem to be associated with any deleterious effect on carbohydrate metabolism in the neonate. Human insulin of recombinant DNA origin is a satisfactory treatment for diabetic pregnancy, is preferable to the use of conventional beef insulins in these patients and may confer a lesser risk of neonatal hypoglycaemia than purified pork insulin.
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pubmed_465_3486
|
pubmed_324_1992
|
A 41-year-old male presented with a rare temporal intraparenchymal neurenteric cyst. A definitive preoperative diagnosis was not possible based upon the neuroradiological features. A complete excision of the cyst was achieved. Histopathology confirmed the diagnosis of a neurenteric cyst, an endodermally derived lesion of the central nervous system.
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10.1016/j.jocn.2010.04.046
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pubmed_238_27162
|
Salt bladders are specialized epidermal structures that halophytes use to store and excrete excess salt. However, the cell wall composition during salt bladder development is unclear, and the functions of salt bladders in a few wild plants remain unexplored. Therefore, the present study examined salt bladder development, cell wall composition, and their roles under salt stress by employing bladder-brushed and unbrushed Chenopodium album plants. We found that the bladder cell of C. album was connected to the epidermal cells through a rectangular stalk cell and developed from the shoot tip and the young leaves. The polysaccharides of salt bladder cell wall showed dynamic distribution at different stages of development. Moreover, salt bladders affected Na+ and K+ accumulation, increased reactive oxygen species scavenging, and improved the osmoregulation and photosynthetic efficiency in leaves, subsequently enhancing the salt tolerance of plants. The findings strengthen our knowledge of the physiological mechanisms of the accessory structures in desert plants, which can be used as a reference for further research at the molecular level.
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10.3389/fpls.2022.989946
|
pubmed_78_15531
|
The spread of antibiotic resistance from farm animals to human pathogens has become a matter of great public health significance, and methods to reduce foodborne pathogenic bacteria without utilizing traditional antibiotics have been sought. Chlorate kills Escherichia coli O157:H7 in vitro and in vivo and has been proposed as a feed additive to be included in food animal rations immediately prior to slaughter to reduce E. coli O157:H7 populations in the animal gastrointestinal tract. This study was designed to examine the effect that the development of chlorate resistance in E. coli O157:H7 has on resistance to 32 medically important antibiotics. Chlorate resistance numerically increased antibiotic resistance in E. coli O157:H7 strain 6058 and strain 933 to six and four antibiotics, respectively, but chlorate resistance affected resistance to only two antibiotics (cefoxotin and sulfadimethoxine) in both strains examined. Based on the fact that chlorate resistant mutants do not appear to compete well in vivo and based on the results of the current study, it appears unlikely that chlorate treatment will result in a dissemination of antibiotic resistance. However, further research is needed to confirm these results.
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10.1089/153531404772914473
|
pubmed_895_16939
|
Sex determination is of paramount importance in forensic anthropology. Numerous anthropological methods have been described, including visual assessments and various measurements of bones. Nevertheless, whatever the method used, the percentage of correct classification of a single bone usually varies between 80% and 95%, due to significant intra- and inter-population variations, and sometimes variations coming from secular trends. DNA is increasingly used in a forensic context. But forensic DNA extraction from bone raises several issues, because the samples are very often badly altered and/or in very small quantity. Nuclear DNA is difficult to get from degraded samples, according to low copy number, at least in comparison with mitochondrial DNA. In a forensic context (as in a paeleoanthropological context) DNA sex determination is usually complicated by the weak amount of DNA, the degraded nature of nucleic acids, the presence of enzymatic inhibitors in DNA extracts, the possible faint amplification of Y band and the risk of contamination during either excavation or manipulation of samples. The aim of this work was to compare three methods of DNA sex determination from bones: procedure #1 using a single PCR amplification, procedure #2 using a double PCR amplification, and procedure #3 adding bleaching for decontamination of the bone, instead of simply rubbing the bone. These processes were applied to samples of bones (49 samples coming from 39 individuals) that were in various states of post mortem alteration. The main results are the following. (i) No DNA could be extracted from three skulls (parietal bones, mastoid process), the compact bone of one rib, and the diaphysis of one femur; (ii) there was a contamination in three skulls; and (iii) the Y band did not appear in two male cases, with one of the three procedures (male tibia, procedure #2) and with procedures #2 and #3 (male femur). This study emphasises the main issue while working with altered bones: the impossibility to extract DNA in some cases, and, worth of all, the contamination of the sample or the faint amplification of Y band which leads to a wrong sex answer. Multiple and significant precautions have to be taken to avoid such difficulties.
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pubmed_895_16939
|
pubmed_85_1422
|
Data are reported showing statistically significant negative correlations between intelligence and family size, position, and income in a sample of 604 adolescent girls in Saudi Arabia. There were no statistically significant correlations or associations between whether the mother or father were deceased or both parents were alive, and whether the parents were living together or were divorced.
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10.1177/0033294116665179
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pubmed_924_19256
|
A number of contaminants in municipal effluent discharges are estrogen agonists to fish. Whereas several in vitro and in vivo techniques have been developed to assess the estrogenic activity of these compounds or ambient environmental samples, previous comparisons of the relative sensitivities of these approaches remain inconclusive. We employed a probabilistic hazard assessment approach using chemical toxicity distributions (CTDs) to perform a novel evaluation of relative sensitivities of six common in vitro and in vivo assays. We predicted that there was an 8.3% (human breast ademocarcinoma cell line, MCF-7, assay), 6.3% (yeast estrogen screen assay), or 1.9% (fish hepatocyte vitellogenin, VTG, assay) probability of detecting a compound in aquatic systems that will elicit an estrogenic response at concentrations at or below 0.1 microg/L, suggesting that the MCF-7 assay was the most sensitive in vitro assay evaluated in this study. The probabilities of eliciting the estrogenic response of VTG induction at a concentration less than 0.1 microg/L in rainbow trout, fathead minnow, and Japanese medaka were determined at 29.9, 26.2, and 18.8%, respectively. Thus, rainbow trout VTG induction was the most sensitive in vivo assay assessed. Subsequently, CTDs may provide a useful technique for hazard assessment of chemical classes for which exposure data are limited and for chemicals with common toxicological mechanisms and modes of action.
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10.1897/08-126.1
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pubmed_146_745
|
OBJECTIVES
Since 1999, HIV testing is routinely offered to all attendees of the sexually transmitted infections (STI) outpatient clinic in Amsterdam, the Netherlands. This study evaluates whether this more active HIV-testing policy increased uptake of HIV testing and awareness of an HIV-positive serostatus among heterosexual attendees.
METHODS
In addition to routine data collected at each STI consultation, data from half-yearly HIV surveys were used from 1994 to 2004. During each survey period, 1000 consecutive attendees are enrolled voluntary and anonymously for HIV testing and are interviewed on previous HIV testing and outcome. Trends in and predictors for uptake of HIV testing as offered during routine STI consultation were analysed by logistic regression. Trends in awareness of an HIV-positive serostatus as obtained from the anonymous HIV surveys were likewise analysed.
RESULTS
The percentage of heterosexual attendees opting for an HIV test during consultation increased from 13% in 1996 to 56% in 2004. However, the proportion of individuals aware of their HIV infection did not change over time and only a minority (19%) of the 108 attendees found HIV-positive in the anonymous surveys were aware of their HIV infection. Persons being or visiting a commercial sex worker, having a non-Dutch ethnicity, lacking health insurance and having an STI diagnosed were less likely to opt for an HIV test.
CONCLUSIONS
Although heterosexual attendees increased their uptake of HIV testing during STI consultation over time, uptake of testing by attendees at risk for HIV infection, such as those infected with an STI, remained low. As a result, the percentage of persons aware of their HIV infection remained low, posing a risk for their individual health and for ongoing HIV transmission. Current testing strategies, therefore, misses the group that most needs testing. Based on these results, 'opt-out' HIV testing is now the standard procedure at the Amsterdam STI clinic.
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10.1093/eurpub/ckm120
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pubmed_39_13787
|
CONTEXT
Congenital hyperinsulinism of infancy (CHI) represents a group of heterogeneous disorders characterized by oversecretion of insulin from pancreatic β-cells causing severe hypoglycemia.
OBJECTIVE
We studied the distribution of genetic causes of CHI in a Czech population.
METHODS
Countrywide collection of patients with CHI included 40 subjects (12 females, median age of diagnosis, 1 wk [interquartile range, 1-612 wk]). We sequenced the ABCC8, KCNJ11, GLUD1, GCK, HADH, UCP2, SLC16A1, HNF4A, and HNF1A genes and investigated structural changes in the ABCC8 gene. We functionally tested novel variants in the ABCC8 gene by Rb(86+) efflux assay and novel variants in the HNF1A gene by transcriptional activation and DNA-binding tests.
RESULTS
We found causal mutations in 20 subjects (50%): 19 carried a heterozygous mutation while one patient was homozygous for mutation in the ABCC8 gene. Specifically, we detected 11 mutations (seven novel) in ABCC8, one novel mutation in KCNJ11, five mutations (two novel) in HNF1A, two novel mutations in HNF4A, and one in GCK. We showed a decrease of activation by diazoxide in mutant KATP channels with novel ABCC8 variants by 41-91% (median, 82%) compared with wild-type (WT) channels and reduced transcriptional activity of mutant HNF1A proteins (2.9% for p.Asn62Lysfs93* and 22% for p.Leu254Gln) accompanied by no DNA-binding ability compared with WT HNF1A.
CONCLUSION
We detected a higher proportion of heterozygous mutations causing CHI compared with other cohorts probably due to lack of consanguinity and inclusion of milder CHI forms. Interestingly, HNF1A gene mutations represented the second most frequent genetic cause of CHI in the Czech Republic. Based on our results we present a genetic testing strategy specific for similar populations.
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10.1210/jc.2015-2763
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pubmed_407_2836
|
STUDY DESIGN
Retrospective cohort study.
OBJECTIVE
To investigate the differences between single- and multilevel degenerative disc diseases (DDDs) treated with cervical arthroplasty.
SUMMARY OF BACKGROUND DATA
The US Food and Drug Administration clinical trials compared arthroplasty with anterior cervical discectomy and fusion for single-level DDD. However, cervical arthroplasty for multilevel DDD is rarely addressed in the literature.
METHODS
A total of 102 consecutive patients who underwent Bryan arthroplasty were divided into either a single- or multilevel group. Clinical outcomes were measured by the visual analogue scale (VAS) of neck and arm, and by the neck disability index with a minimum follow-up of 25 months. Every patient had radiographical evaluations, and computed tomography.
RESULTS
Eighty-six patients (84.3%) completed the follow-up with a mean time of 38.3 ± 8.7 months. Postoperatively, there were significant improvements in clinical outcomes (i.e., VAS neck, VAS arm, and neck disability index) at each time point of evaluation (i.e., 3-, 6-, 12-, and 24 mo postoperation). The sex composition and clinical outcome improvements between the single- and multilevel groups were not significantly different. The multilevel group was older (51.3 ± 8.6 vs. 46.3 ± 11.2 yr; P = 0.02), had more intraoperative blood loss (218.0 ± 182.4 vs. 102.8 ± 79.2 mL; P = 0.001), and demonstrated a higher rate of heterotopic ossification (HO) than the single-level group (66.0% vs. 25.0%; P < 0.001). The majority (97.7%) of the artificial discs in this series remained mobile despite HO.
CONCLUSION
Clinical outcomes of cervical arthroplasty in multilevel spondylosis are similar to single-level outcomes. However, the significantly higher rate of HO found in multilevel arthroplasty and its long-term effect warrant further investigation.
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10.1097/BRS.0b013e318265a126
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pubmed_929_16900
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In recent years, peroxisome proliferator-activated receptor-γ (PPARγ) has been intensively studied. Because its activation is often associated with changes in the expression level of various apoptotic genes, many studies have emphasized the role of PPARγ as an important anticancer agent. However, in different types of cancer, different genes are influenced by PPARγ action. Previous studies showed that conjugated linoleic acid (CLA) was able to induce apoptosis, upregulate PPARG gene expression and activate PPARγ protein in certain human cancer cell lines. Moreover, some PPARγ agonists inhibited the growth of human lung cancer cells through the induction of apoptosis. Nevertheless, the impact of CLA on PPARγ mRNA and protein levels in non-small cell lung cancer (NSCLC) cell lines has not been investigated thus far. Therefore, in our study, we analysed the influence of the c9,t11 linoleic acid isomer on the expression of PPARG and other genes involved in the apoptotic response (BCL-2, BAX, and CDKN1A) in two NSCLC cell lines of different histological origin (A549 and Calu-1) and in normal human bronchial epithelial Beas-2B cells. Cells were treated with several doses of c9,t11 CLA, followed by RNA and protein isolation, cDNA synthesis, real-time quantitative PCR (RT-qPCR) and Western blot analysis. We showed that the investigated CLA isomer was able to enhance the expression of PPARγ in the examined cell lines and alter the mRNA and protein levels of genes involved in apoptosis. Fluorescent staining and MMT assay revealed the antiproliferative potential of CLA as well as its ability to activate pathways that lead to cell death.
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10.1007/s11010-020-03689-8
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pubmed_852_13923
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Spt10 is a putative acetyltransferase of Saccharomyces cerevisiae that directly activates the transcription of histone genes. Deletion of SPT10 causes a severe slow growth phenotype, showing that Spt10 is critical for normal cell division. To gain insight into the function of Spt10, we identified mutations that impair or improve the growth of spt10 null (spt10Δ) mutants. Mutations that cause lethality in combination with spt10Δ include particular components of the SAGA complex as well as asf1Δ and hir1Δ. Partial suppressors of the spt10Δ growth defect include mutations that perturb cell-cycle progression through the G1/S transition, S phase, and G2/M. Consistent with these results, slowing of cell-cycle progression by treatment with hydroxyurea or growth on medium containing glycerol as the carbon source also partially suppresses the spt10Δ slow-growth defect. In addition, mutations that impair the Lsm1-7-Pat1 complex, which regulates decapping of polyadenylated mRNAs, also partially suppress the spt10Δ growth defect. Interestingly, suppression of the spt10Δ growth defect is not accompanied by a restoration of normal histone mRNA levels. These findings suggest that Spt10 has multiple roles during cell division.
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10.1534/g3.112.005389
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pubmed_336_12016
|
Vibrissal whisking is often employed to track facial nerve regeneration in rats; however, we have observed similar degrees of whisking recovery after facial nerve transection with or without repair. We hypothesized that the source of non-facial nerve-mediated whisker movement after chronic denervation was from autonomic, cholinergic axons traveling within the infraorbital branch of the trigeminal nerve (ION). Rats underwent unilateral facial nerve transection with repair (N=7) or resection without repair (N=11). Post-operative whisking amplitude was measured weekly across 10weeks, and during intraoperative stimulation of the ION and facial nerves at ⩾18weeks. Whisking was also measured after subsequent ION transection (N=6) or pharmacologic blocking of the autonomic ganglia using hexamethonium (N=3), and after snout cooling intended to elicit a vasodilation reflex (N=3). Whisking recovered more quickly and with greater amplitude in rats that underwent facial nerve repair compared to resection (P<0.05), but individual rats overlapped in whisking amplitude across both groups. In the resected rats, non-facial-nerve-mediated whisking was elicited by electrical stimulation of the ION, temporarily diminished following hexamethonium injection, abolished by transection of the ION, and rapidly and significantly (P<0.05) increased by snout cooling. Moreover, fibrillation-related whisker movements decreased in all rats during the initial recovery period (indicative of reinnervation), but re-appeared in the resected rats after undergoing ION transection (indicative of motor denervation). Cholinergic, parasympathetic axons traveling within the ION innervate whisker pad vasculature, and immunohistochemistry for vasoactive intestinal peptide revealed these axons branching extensively over whisker pad muscles and contacting neuromuscular junctions after facial nerve resection. This study provides the first behavioral and anatomical evidence of spontaneous autonomic innervation of skeletal muscle after motor nerve lesion, which not only has implications for interpreting facial nerve reinnervation results, but also calls into question whether autonomic-mediated innervation of striated muscle occurs naturally in other forms of neuropathy.
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pubmed_336_12016
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pubmed_393_8850
|
The grating acuity of 197 infants from 1 week to 53 weeks of age was measured using the visual evoked potential (VEP) in response to counterphase grating stimulation. The gratings were presented as a 10 sec spatial frequency sweep which spanned the acuity limit. The amplitude and phase of the second harmonic response were extracted by discrete Fourier analysis. The VEP amplitude versus spatial frequency function showed narrow spatial frequency tuning with amplitude peaks at one or more spatial frequencies. The phase of the response at medium to high spatial frequencies was generally constant at a spatial frequency peak, followed by a progressive phase lag with increasing spatial frequency. Grating acuity was estimated by linear extrapolation to zero microvolts of the highest spatial frequency peak in the VEP amplitude versus spatial frequency function. This visual acuity estimate increased from a mean of 4.5 c/deg during the first month to about 20 c/deg at 8-13 months of age. The VEP acuities at 1 month are a factor of three to five higher than previously reported for pattern reversal or pattern appearance stimuli. By 8 months VEP grating resolution was not reliably different from adult levels in the same apparatus.
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10.1016/0042-6989(85)90217-2
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pubmed_393_12150
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The energy-dependent, respiration-supported uptake and the uncoupler- or Na+-induced release of Ca2+ and Mn2+ by mitochondria from rat liver, heart and brain were investigated, using as indicators radioisotopes (45Ca and 54Mn), proton ejection, oxygen consumption, nicotinamide nucleotide oxidation-reduction and, in the case of Ca2+, the metallochromic dye Arsenazo III. Ca2+ uptake in the presence of Pi was rapid in mitochondria from liver and brain, and less rapid in those from heart. Mn2+ uptake was much slower than that of Ca2+ in liver and heart, but only slightly slower in brain. When added together, Ca2+ accelerated the uptake of Mn2+, and Mn2+ retarded the uptake of Ca2+, by mitochondria from all three tissues. When Mn2+ was present during Ca2+ uptake, its own uptake remained accelerated even after Ca2+ uptake was terminated. Mg2+, which was not taken up, inhibited Ca2+ uptake by mitochondria from all three tissues, and, when present during Ca2+ uptake, accelerated the subsequent uptake of Mn2+. The uncoupler CCCP induced a release of both Ca2+ and Mn2+ from all three sources of mitochondria; yet, release of Mn2+ took place only in the absence of Pi. The release followed the same pattern as the uptake, i.e., Ca2+ accelerated the release of Mn2+ and Mn2+ retarded the release of Ca2+. Na+ induced a release of both Ca2+ and Mn2+ from heart and brain but not from liver mitochondria; again, Mn2+ release occurred only in the absence of Pi. The Na+-induced release of Ca2+ was inhibited by Mn2+, but the Na+-induced release of Mn2+ was not accelerated by Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1016/s0300-9084(85)80133-4
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pubmed_789_13606
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The objective of this study was to use pedigree analysis to evaluate the population structure and genetic variability in the Murrah dairy breed of water buffalo (Bubalus bubalis) in Brazil. Pedigree analysis was performed on 5,061 animals born between 1972 and 2002. The effective number of founders (fe) was 60, representing 6.32 % of the potential number of founders. The effective number of ancestors (fa) was 36 and the genetic contribution of the 17 most influent ancestors explained 50 % of the genetic variability in the population. The ratio fe/fa (effective number of founders/effective number of ancestors), which expresses the effect of population bottlenecks, was 1.66. Completeness level for the whole pedigree was 76.8, 49.2, 27.7, and 12.8 % for, respectively, the first, second, third, and fourth known parental generations. The average inbreeding values for the whole analyzed pedigree and for inbreed animals were, respectively, 1.28 and 7.64 %. The average relatedness coefficient between individuals of the population was estimated to be 2.05 %-the highest individual coefficient was 10.31 %. The actual inbreeding and average relatedness coefficient are probably higher than estimated due to low levels of pedigree completeness. Moreover, the inbreeding coefficient increased with the addition of each generation to the pedigree, indicating that incomplete pedigrees tend to underestimate the level of inbreeding. Introduction of new sires with the lowest possible average relatedness coefficient and the use of appropriate mating strategies are recommended to keep inbreeding at acceptable levels and increase the genetic variability in this economically important species, which has relatively low numbers compared to other commercial cattle breeds. The inclusion of additional parameters, such as effective number of founders, effective number of ancestors, and fe/fa ratio, provides better resolution as compared to the inclusion of inbreeding coefficient and may help breeders and farmers adopt better precautionary measures against inbreeding depression and other deleterious genetic effects.
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10.1007/s11250-012-0153-x
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pubmed_1096_1313
|
The present study aimed to estimate the blood-brain barrier (BBB) permeability of Gualou Guizhi granules (GLGZG) in normal rats and in rat models of ischemia/reperfusion (I/R) injury, and to examine the neuroprotective effects of GLGZG. A sensitive high‑performance liquid chromatography-quadrupole-time of flight-mass spectrometry analytical method was developed to determinate the components of GLGZG in the plasma and brain tissue. Middle cerebral artery occlusion (MCAO) in rats served as a model of in vivo I/R. Citrulline, gallic acid, albiflorin, peoniflorin, liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizinic acid rapidly passed into the bloodstream. Citrulline, albiflorin, peoniflorin, liquiritin apioside, liquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizinic acid also passed the BBB and reached the brain tissue of MCAO rats, while isoliquiritigenin and glycyrrhizinic acid were not detected in the brain tissue of the normal rats. The potential neuroprotective effect of GLGZG was determined in MCAO rats. The intragastric administration of GLGZG following reperfusion of rats for 2 h decreased the neurological defects and infarction volume, attenuated pathological changes of brain tissue and exerted a significant protective effect in cerebral ischemia injury. In conclusion, certain components of GLGZG passed through the BBB, particularly following cerebral ischemia injury, and this may be therapeutically effective for the treatment of cerebral ischemia injury in the human brain.
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10.3892/mmr.2015.3520
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pubmed_928_20441
|
The results of IVF-ETR strongly suggest the existence of implantation failure of unknown etiology. A selected group of 41 couples with long-standing infertility who had one or more failed IVF-ETR cycles were analysed for HLA antigen sharing, and 19 wives were immunized with their husband's purified lymphocytes just before the subsequent trial. Both the number and frequency of shared HLA antigens in these patients were significantly increased, compared with control couples of normal fertility (p < 0.05). After immunization, 7 patients (36.8%) conceived by IVF-ETR, and 5 (71.4%) delivered a healthy baby at term. The pregnant couples shared significantly fewer HLA antigens compared with those who failed to conserve (p < 0.05). Interestingly, the MLR blocking effect was enhanced in the pregnant group after immunization, suggesting the induction of blocking antibodies which are believed essential for the survival of the developing fetus. In contrast, the blocking effect was rather decreased in the nonpregnant group. These results implicate that HLA sharing and inadequate maternal anti-paternal immunity may be related to implantation failure, and immunotherapy can be used to potentiate the maternal immune response, leading to successful implantation in selected patients.
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pubmed_928_20441
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pubmed_543_5722
|
Two rabbits immunized with a portion of glutamate receptor (GluR) subunit GluR3 (amino acids 245-457) exhibited seizure-like behaviors, suggesting that antibodies to GluR3 may modulate neuronal excitability. Using whole-cell recording, rabbit GluR3 antisera were tested on cultured fetal mouse cortical neurons. In a subset of kainate-responsive neurons, miniperfusion of antisera and IgG evoked currents that were blocked by CNQX. Immunoreactivity to synthetic peptides prepared to subregions GluR3A (amino acids 245-274) and GluR3B (amino acids 372-395) was present in both rabbit sera. Peptide GluR3B, but not GluR3A, specifically blocked antisera- and IgG-evoked currents. Similar receptor activation and anti-GluR3 reactivity was present in sera from patients with active Rasmussen's encephalitis, an intractable pediatric epilepsy. Thus, antibodies to GluR3 define a region involved in agonist binding and specific receptor activation. These data suggest that antibodies to neuronal receptors can function as agonists and that autoantibodies to GluRs may be highly specific neurotoxicants in some neurological diseases.
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10.1016/0896-6273(95)90219-8
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pubmed_589_8944
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A combination of (bromodifluoromethyl)trimethylsilane (Me3SiCF2Br), triphenylphosphine, and DMPU serves as a source of difluorinated phosphorus ylide Ph3P═CF2 under mild conditions. The system was used to effect nucleophilic difluoromethylation of ketones and nitro alkenes. The reaction efficiency is believed to be associated with Lewis acidic activation of the substrates by a silylium species formed upon generation of the phosphorus ylide.
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10.1021/acs.orglett.6b01641
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pubmed_567_22053
|
BACKGROUND
CTLA4IgG that binds to B7 effectively inhibits the signaling of CD28/B7 pathway and induces antigen-specific T-cell unresponsiveness in vitro and in vivo. We examined whether the development of obliterative bronchiolitis in a murine heterotopic airway transplantation model is T cell dependent and whether CTLA4IgG abrogates the development of obliterative bronchiolitis.
METHODS
Tracheae with main bronchi from C3H/He (H2k), BALB/C (H2d), or C57BL/6 (H2b) mice were transplanted heterotopically into subcutaneous pockets on the backs of BALB/C or BALB/C nu/nu mice on day 0. Recipient mice were untreated or intraperitoneally treated with either CTLA4IgG or human IgG with different time and dose schedules.
RESULTS
The development of obliterative bronchiolitis, which leads to luminal obliteration by fibrous tissue in a murine heterotopic airway transplantation model, was T cell dependent and the development of obliterative bronchiolitis was significantly abrogated by the CTLA4IgG treatment. However, the normal ciliated columnar respiratory epithelial cells in allografts were lost and replaced by flattened attenuated epithelial cells even after the CTLA4IgG treatment. We further demonstrated that CTLA4IgG treatment did not result in the induction of donor-specific unresponsiveness.
CONCLUSIONS
We demonstrated that the development of obliterative bronchiolitis in a murine heterotopic airway model involves both CD28/B7-dependent and -independent processes. The luminal obliteration by fibrous tissue is clearly CD28/B7 dependent and can be inhibited by CTLA4IgG. The luminal obliteration of allografted trachea by fibrous tissues and the loss of ciliated columnar respiratory epithelial cells represent distinct disease processes.
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10.1097/00007890-200003150-00012
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pubmed_437_19782
|
It has been argued that cooperative behavior in the plant-mycorrhizal mutualism resembles trade in a market economy and can be understood using economic tools. Here, we assess the validity of this "biological market" analogy by investigating whether a market mechanism--that is, competition between partners over the price at which they provide goods--could be the outcome of natural selection. Then, we consider the conditions under which this market mechanism is sufficient to maintain mutualistic trade. We find that: (i) as in a market, individuals are favored to divide resources among trading partners in direct relation to the relative amount of resources received, termed linear proportional discrimination; (ii) mutualistic trade is more likely to be favored when individuals are able to interact with more partners of both species, and when there is a greater relative difference between the species in their ability to directly acquire different resources; (iii) if trade is favored, then either one or both species is favored to give up acquiring one resource directly, and vice versa. We then formulate testable predictions as to how environmental changes and coevolved responses of plants and mycorrhizal fungi will influence plant fitness (crop yields) in agricultural ecosystems.
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10.1111/evo.12466
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pubmed_362_5050
|
BACKGROUND
Stomach adenocarcinoma (STAD) is one of the most common and deadly cancers worldwide. Recent evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNA) is associated with different hallmarks of cancer. lncRNAs also were suggested as novel promising biomarkers for cancer diagnosis and prognosis. Despite these previous investigations, the expression pattern, diagnostic role, and hallmark association of lncRNAs in STAD remain unclear.
RESULTS
In this study, The STAD lncRNA-mRNA network was constructed based on RNAs that differentially expressed among tumor and normal samples and had a strong expression correlation with others. The high degree nodes of the network were associated with overall survival. In addition, we found that the hubs' regulatory roles have previously been confirmed in different types of cancers by literature. For example, the HCG22 hub inhibited cell proliferation and invasion and induced apoptosis in oral squamous cell carcinoma (OSCC) cells. The levels of PCNA, Vimentin, and Bcl2 were decreased and E-cadherin and Bax expression was elevated in OSCC cells after HCG22 overexpression. Additionally, HCG22 overexpression inhibited the Akt, mTOR, and Wnt/β-catenin pathways. Then lncRNAs were mapped to their related GO terms and cancer hallmarks. Based on these mappings, we predict the hallmarks that might be associated with each lncRNA. Finally, the literature review confirmed our prediction. Among the 20 lncRNAs of the STAD network, 11 lncRNAs (LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1, ENSG00000262756) demonstrated expression correlation with overall survival (OS). Based on expression analysis, survival analysis, hallmark associations, and literature review, LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1 plays a regulatory role in STAD. For example, our prediction of association between C5orf66-AS1 expression dysregulation and "sustaining proliferative signal" and "Activating invasion and metastasis" has been confirmed in STAD, OSCC and cervical cancer. Finally, we developed a lncRNA signature with SOX21-AS1 and LINC02560, which classified patients into high and low-risk subgroups with significantly different survival outcomes. The mortality rate of the high-risk patients was significantly higher compared to the low-risk patients (28/1% vs 60.13).
CONCLUSION
These findings help in designing more precise and detailed experimental studies to find STAD biomarkers and therapeutic targets.
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10.1186/s12864-022-08578-6
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pubmed_658_10419
|
Reduction of large artery distensibility has several adverse consequences for the cardiovascular system. This paper reviews the evidence obtained by measuring distensibility through quantification of changes in arterial diameter versus blood pressure changes at large elastic and middle size muscle artery sites. Evidence is available that arterial distensibility is reduced in conditions as varied as hypercholesterolemia, hypertension, diabetes and congestive heart failure. In some conditions (e.g. hypertension) the alterations are not uniformly distributed in arteries of different structure and size whereas in others (e.g. diabetes and heart failure) they are widespread. In diabetes evidence is available that distensibility changes occur early in the course of the disease. Evidence is also available that in all above conditions treatment can improve arterial distensibility thereby reversing the initial abnormality. This appears to be due to a variable combination of structural and functional factors. Technical ability to determine their precise role in distensibility changes in humans is limited, however.
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10.1097/00004872-200210000-00001
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pubmed_859_16877
|
MOTIVATION
Intragenic exonic deletions are known to contribute to genetic diseases and are often flanked by regions of homology.
RESULTS
In order to get a more clear view on these interspersed repeats encompassing a coding sequence, we have developed EDIR (Exome Database of Interspersed Repeats) which contains the positions of these structures within the human exome. EDIR has been calculated by an inductive strategy, rather than by a brute force approach and can be queried through an R/Bioconductor package or a web interface allowing the per gene rapid extraction of homology flanked sequences throughout the exome.
AVAILABILITY
The code used to compile EDIR can be found at https://github.com/lauravongoc/EDIR. The full data set of EDIR can be queried via an Rshiny application at http://193.70.34.71:3857/edir/. The R package for querying EDIR is called "EDIRquery" and is available on Bioconductor. The full EDIR data set can be downloaded from https://osf.io/m3gvx/ or http://193.70.34.71/EDIR.tar.gz.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
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10.1093/bioinformatics/btac771
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pubmed_896_14221
|
Gliomas are differentiated into two major disease subtypes, astrocytoma or oligodendroglioma, which are then characterized as either IDH (isocitrate dehydrogenase)-wild type or IDH-mutant due to the dramatic differences in prognosis and overall survival. Here, we investigated the genetic background of IDH1-mutant gliomas using the Catalogue of Somatic Mutations in Cancer (COSMIC) database. In astrocytoma patients, we found that IDH1 is often co-mutated with TP53, ATRX, AMBRA1, PREX1, and NOTCH1, but not CHEK2, EGFR, PTEN, or the zinc finger transcription factor ZNF429. The majority of the mutations observed in these genes were further confirmed to be either drivers or pathogenic by the Cancer-Related Analysis of Variants Toolkit (CRAVAT). Gene expression analysis showed down-regulation of DRG2 and MSN expression, both of which promote cell proliferation and invasion. There was also significant over-expression of genes such as NDRG3 and KCNB1 in IDH1-mutant astrocytoma patients. We conclude that IDH1-mutant glioma is characterized by significant genetic changes that could contribute to a better prognosis in glioma patients.
|
10.3390/cancers13174299
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pubmed_507_15882
|
An enhancement of the electroluminescence (EL) from nanoscale silicon p(+)-n junctions made with an anodic aluminum oxide (AAO) pattern was demonstrated. The nanoporous AAO pattern with a pore density of 1.4 x 10(10) cm(-2) and a pore diameter of 50 +/- 10 nm was fabricated by the two-step anodic oxidation method on a n-type silicon wafer. The nanoscale AAO patterned Si p(+)-n junctions achieved an EL enhancement factor up to about 5 compared to the unpatterned Si p(+)-n junctions. The enhancement may originate from a reduction of nonradiative recombination due to partial passivation of the Si surface by the AAO pattern and improvement of the light extraction due to surface nanotextures.
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10.1088/0957-4484/21/2/025301
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pubmed_345_24019
|
This Minireview summarizes a variety of intriguing catalytic studies accomplished by employing unsupported, either solubilized or freely mobilized, and small organic ligand-capped palladium nanoparticles as catalysts. Small organic ligands are gaining more attention as nanoparticle stabilizers and alternates to larger organic supports, such as polymers and dendrimers, owing to their tremendous potential for a well-defined system with spatial control in surrounding environments of reactive surfaces. The nanoparticle catalysts are grouped depending on the type of surface stabilizers with reactive head groups, which include thiolate, phosphine, amine, and alkyl azide. Applications for the reactions such as hydrogenation, alkene isomerization, oxidation, and carbon-carbon cross coupling reactions are extensively discussed. The systems defined as "ligandless" Pd nanoparticle catalysts and solvent (e.g. ionic liquid)-stabilized Pd nanoparticle catalysts are not discussed in this review.
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10.1002/cctc.201402865
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pubmed_919_6313
|
Hybridization and their application in the DNA array technology. DNA hybridization arrays measure simultaneously the expression of several genes. First, a known DNA sequence (probe) is fixed on a firm basis. Then the complementer sequence (target sequence) is linked to it during the hybridization process. The target sequence extracted from biological samples is fluorescently, enzimatically or radioactively labeled before detection. Higher expression results in higher signal in the detection system. Unlabeled DNA strands can also be detected, as the electronic and optical characteristics of the DNA is altered after complementer hybridization. In this review we summarize the basics of hybridisation and its newest application area in the DNA array systems.
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pubmed_919_6313
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pubmed_337_22094
|
Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = -0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction.
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10.1097/MD.0000000000003400
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pubmed_855_5929
|
The effects of cadmium exposure on rat lung type 2 cells were evaluated by morphological and biochemical examinations. The results showed dose dependent reduction in the marker enzyme (alkaline phosphatase), changes in cell membranes and in the antioxidant status.
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pubmed_855_5929
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pubmed_482_7179
|
Marigold (Calendula calypso) is a multipurpose ornamental plant, but its cadmium (Cd) tolerance and phytoremediation potential is unknown. The proposed study was carried out to unravel Cd partitioning, physiological and oxidative stress responses of C. calypso grown under Cd stress. Plants were grown for four months in pots having different soil Cd levels: 0, 25, 50, 75, and 100 mg kg-1 soil. Plant growth, biomass, photosynthetic pigments, leaf water contents, stomatal conductance, and membrane stability index were not decreased at 25 mg kg-1 Cd. At higher levels of Cd stress, activities of antioxidant enzymes (SOD, APX, CAT, POD) increased to mitigate H2O2 and lipid peroxidation. Cadmium uptake in plants increased with increasing soil Cd levels, and roots accumulated a greater portion of Cd, followed by shoots and flowers, respectively. On the basis of Cd accumulation and its tolerance, it was determined that C. calypso can be successfully grown for phytostabilization of Cd contaminated soils.
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10.1007/s00128-020-02934-6
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pubmed_105_20304
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Quasi two-dimensional (Q-2D) perovskite cells have attracted much attention due to their excellent stability compared to their 3D counterparts. However, the Q-2D perovskite thin films prepared by the solution method have been confirmed to be a mixture of small-n phases and large-n phases instead of a pure phase, where the amount and distribution of these phases have a great significance on the performance of Q-2D perovskite solar cells. Here, commercialized 3D perovskite powder was simply added to an ACI perovskite precursor solution to get a uniform and closely connected heterostructure in which the large-n phases can work as pathways for charge transfer. The characterization results of the films and devices show that the appropriate amount of MAPbI3 in the precursor solution could distribute the 3D phases homogeneously within the final film to promote the photovoltaic performance of the devices. Consequently, the power conversion efficiency of the Q-2D ACI perovskite solar cell has been increased from 10.4% to 13.82% (with a 32.8% performance improvement).
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10.1039/d2dt00966h
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pubmed_872_10269
|
BACKGROUND AND PURPOSE
The goal of this study was to assess the specific influence of stroke etiology on rehabilitation results.
METHODS
This was a case-control study of 270 inpatients with sequelae of first stroke who were enrolled in homogeneous subgroups and matched for stroke severity, basal disability, age (within 1 year), sex, and onset admission interval (within 3 days) who were different only in terms of stroke origin, infarction versus hemorrhage. We compared the groups' length of stay, efficiency and effectiveness of treatment, and percentage of low and high responder patients. Odds ratios of dropouts and of low and high therapeutic response were also quantified.
RESULTS
Compared with ischemic patients, hemorrhagic patients had significantly higher Canadian Neurological Scale and Rivermead Mobility Index scores at discharge; higher effectiveness and efficiency on the Canadian Neurological Scale, Barthel Index, and Rivermead Mobility Index; and a higher percentage of high responders on the Barthel Index. Hemorrhagic patients showed a probability of a high therapeutic response on the Barthel Index that was approximately 2.5 times greater than that of ischemic patients (odds ratio, 2.48; 95% confidence interval, 1.19 to 5.20; accuracy on prediction, 87.06%).
CONCLUSIONS
The results of this study provide further evidence of better functional prognosis in stroke survivors with hemorrhagic stroke.
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10.1161/01.STR.0000102902.39759.D3
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pubmed_229_10542
|
Second primary breast cancer is of importance because of the increasing incidence of first primary breast cancer and improved survival. There is lack of information on the disease in Canada. We studied 14,220 women with a first primary breast cancer (invasive only) diagnosed during the period from 1970 to 1997, in Manitoba, Canada. A breast cancer was considered to be a second primary if it was an invasive lesion diagnosed at least six months after the diagnosis of an initial primary breast cancer. The incidence rate of second primary breast cancer was approximately six per 1,000 person-years, and the cumulative incidence during the 28-year study period was 14.3%. Average age at diagnosis of first primary breast cancer had increased significantly since 1970. The incidence was higher in 1975-1979, and there was no significant difference among other study periods after adjustment for the age at diagnosis of first primary breast cancer. Standardized incidence ratios showed no significant difference among six age groups after adjusting for calendar year. However, women with a first primary breast cancer had an increased risk of developing a second primary breast cancer compared with the risk of developing a first primary breast cancer among the general female population. The SIR was markedly greater among women who had a first primary breast cancer before the age of 40 years, and decreased significantly with increasing age at diagnosis of first primary breast cancer. The data provide epidemiological information on second primary breast cancer risk for the general female population in Manitoba, Canada.
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10.1023/a:1010665603732
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pubmed_596_784
|
The phonon modes of crystalline benzoic acid have been investigated using terahertz time-domain spectroscopy, rigid molecule atom-atom model potential and plane-wave density functional theory lattice dynamics calculations. The simulation results show good agreement with the measured terahertz spectra and an assignment of the terahertz absorption features of benzoic acid is made with the help of both computational methods. Focussing on the strongest interactions in the crystal, we describe each vibration in terms of distortions of the benzoic acid hydrogen bonded dimers that are present in the crystal structure. The terahertz spectrum is also shown to be highly sensitive to the location of the carboxylic acid hydrogen atoms in the cyclic hydrogen-bonded dimers and we have systematically explored the influence of the observed disorder in the hydrogen atom positions on the lattice dynamics.
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10.1039/b926536h
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pubmed_472_13210
|
PURPOSE
Some data indicate that first-generation highly cross-linked polyethylene (HXLPE) can oxidise in vivo and is associated with reduced mechanical properties. To overcome these limitations, a natural anti-oxidant vitamin E has been added to HXLPE to preserve the mechanical properties and decrease oxidative degradation whilst conserving high wear resistance. We hypothesised that after a minimal three years of follow-up the use of vitamin E-blended HXLPE would result in lower radiographic wear when compared with ultra-high molecular weight polyethylene (UHMWPE).
METHODS
One hundred patients were randomised to receive hybrid total hip arthroplasty (THA) using a monoblock cementless acetabular component made either of UHMWPE or vitamin E-blended HXLPE. All other parameters were identical in both groups. Complete follow-up was available for 74 of these patients. Femoral head penetration was measured using a validated computer-assisted method.
RESULTS
The median creep measured 0.111 mm (range, -0.576 - +0.444 mm) in the vitamin E-blended group versus 0.170 mm (range, -0.861 - +0.884 mm) in the UHMWPE group (difference of medians, 0.059; p = 0.046). The median steady state penetration rate was -0.008 mm/year (range, -0.88 - +0.64 mm/year) in the vitamin E-blended group versus 0.133 mm/year (range, -0.84 - +0.85 mm/year) in the UHMWPE group (difference of medians 0.141, p = 0.043).
CONCLUSIONS
This study demonstrated that femoral head penetration was lower when using vitamin E-blended HXLPE when compared with UHMWPE, with a steady-state penetration rate far below the osteolysis threshold. Longer-term follow-up is needed to warrant whether wear reduction will generate less occurrence of osteolysis and aseptic loosening.
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10.1007/s00264-016-3320-2
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pubmed_77_19881
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The permeability of newly formed blood vessels in proliferative diabetic retinopathy at different stages of development was correlated with their ultrastructural features. The young proliferating vessels were much more permeable to fluorescein than were the older vessels. Transmission electron microscopy revealed that the blood vessels within the young intravitreal proliferating fronds had intermediate interendothelial junctions, whereas the blood vessels within the old neovascular preretinal membranes had tight interendothelial junctions of the macula occludens type. Fenestrations were observed only rarely in the endothelial wall of either the young or the older proliferating vessels. We conclude that the principal route of fluorescein leakage from the newly formed blood vessels in proliferative diabetic retinopathy is via the interendothelial clefts.
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pubmed_77_19881
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pubmed_85_8978
|
This article explores the impact of social media on child development and family health. Why do we allow our children to use social media sites before their privacy policies allow? Why do we let them lie about their ages to use these sites? What is it about technology that lets us bend these rules in a way we would never do in the unplugged world? Gaining insight into the answers to these questions and what is positive and negative about social media and the digital world allows us to talk to families about this world, allay their concerns, and keep children of all age safe when using social media.
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pubmed_85_8978
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pubmed_939_4422
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The construction of C-N bonds by free radical reactions represents a powerful synthetic approach for direct C-H amidations of arenes or heteroarenes. Developing efficient and more environmentally friendly synthetic methods for C-H amidation reactions remains highly desirable. Herein, metal-free electrochemical oxidative dehydrogenative C-H amidations of heteroarenes with N-alkylsulfonamides have been accomplished. The catalyst- and chemical-oxidant-free C-H amidation features an ample scope and employs electricity as the green and sole oxidant. A variety of heteroarenes, including indoles, pyrroles, benzofuran and benzothiophene, thereby underwent this C(sp2 )-H nitrogenation. Cyclic voltammetry studies and control experiments provided evidence for nitrogen-centered radicals being directly generated under metal-free electrocatalysis.
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10.1002/chem.202004229
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pubmed_635_6817
|
BACKGROUND
Inflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups.
METHODS
Serum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay.
RESULTS
The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA.
CONCLUSIONS
These results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer.
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10.1371/journal.pone.0123985
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pubmed_1092_21440
|
GTPases of the Ras superfamily regulate a wide variety of cellular processes including vesicular transport and various secretory pathways of the cell. ADP - ribosylation factor (ARF) belongs to one of the five major families of the Ras superfamily and serves as an important component of vesicle formation and transport machinery of the cells. The binding of GTP to these Arfs and its subsequent hydrolysis, induces conformational changes in these proteins leading to their enzymatic activities. The dimeric form of Arf is associated with membrane pinch-off during vesicle formation. In this report, we have identified an arf gene from the unicellular green alga Chlamydomonas reinhardtii, CrArf, and showed that the oligomeric state of the protein in C. renhardtii is modulated by the cellular membrane environment of the organism. Protein cross-linking experiments showed that the purified recombinant CrArf has the ability to form a dimer. Both the 20-kDa monomeric and 40-kDa dimeric forms of CrArf were recognized from Chlamydomonas total cell lysate (CrTLC) and purified recombinant CrArf by the CrArf specific antibody. The membranous environment of the cell appeared to facilitate dimerization of the CrArf, as dimeric form was found exclusively associated with the membrane bound organelles. The subcellular localization studies in Chlamydomonas suggested that CrArf mainly localized in the cytosol and was mislocalized in vesicle transport machinery inhibitor treated cells. This research sheds light on the importance of the cellular membrane environment for regulating the oligomeric state of CrArf protein in this organism and associated functional role.
|
10.1111/jpy.12245
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pubmed_306_10914
|
Little is known about the evolution, diversity, and functional significance of secondary metabolites in reproductive plant parts, particularly fruits and seeds of plants in natural ecosystems. We compared the concentration and diversity of amides among six tissue types of Piper reticulatum: leaves, roots, flowers, unripe fruit pulp, ripe fruit pulp, and seeds. This represents the first detailed description of amides in P. reticulatum, and we identified 10 major and 3 minor compounds using GC/MS and NMR analysis. We also detected 30 additional unidentified minor amide components, many of which were restricted to one or a few plant parts. Seeds had the highest concentrations and the highest diversity of amides. Fruit pulp had intermediate concentrations and diversity that decreased with ripening. Leaves and roots had intermediate concentrations, but the lowest chemical diversity. In addition, to investigate the potential importance of amide concentration and diversity in plant defense, we measured leaf herbivory and seed damage in natural populations, and examined the relationships between amide occurrence and plant damage. We found no correlations between leaf damage and amide diversity or concentration, and no correlation between seed damage and amide concentration. The only relationship we detected was a negative correlation between seed damage and amide diversity. Together, our results provide evidence that there are strong selection pressures for fruit and seed defense independent of selection in vegetative tissues, and suggest a key role for chemical diversity in fruit-frugivore interactions.
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10.1007/s10886-013-0362-4
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pubmed_408_14753
|
For lens implantation a deep anterior chamber is required. In our experience this is best accomplished by mechanical compression to reduce the volume of the vitreous. Following extraction of the lens the anterior chamber fills spontaneously with air. Intraoperative damage to the corneal endothelial cells caused by contact with the pseudophakos can thus be avoided. The procedure also facilitates iris fixation sutures, excision of the anterior lens capsules, irrigation and aspiration.
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10.1055/s-2008-1055060
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pubmed_829_22688
|
Ligands specific to cell surface receptors have been heavily investigated in cancer research. Phage display technology is a powerful tool in this field and may impact clinical issues including functional diagnosis and targeted drug delivery. In this study, a hepatocellular carcinoma cell line (HepG2) and a normal hepatocyte line (L-02) were used to carry out subtractive screening in vitro with a phage display-7 peptide library. After four rounds of panning, there was an obvious enrichment for the phages specifically binding to the HepG2 cells, and the output/input ratio of phages increased about 976-fold (from 0.3x10(-7) to 292.8x10(-7)). A group of peptides capable of binding specifically to the hepatoma cells were obtained, and the affinity of these peptides to the targeting cells and tissues was studied. Through a cell-based ELISA, immunocytochemical staining, immunohistochemical staining, and immunofluorescence, the S1 phage and synthetic peptide HCBP1 (sequence FQHPSFI) were shown to bind to the tumor cell surfaces of two hepatoma cell lines and biopsy specimens, but not to normal hepatocytes, other different cancer cells, or nontumor liver tissues. In conclusion, the peptide HCBP1 may be a potential candidate for targeted drug delivery in therapy of hepatoma cancer.
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10.2119/2006–00115.Zhang
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pubmed_600_17522
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Cold is a kind of mild and self-limiting viral illness that is considered as a prevalent disease with global occurrence and is caused by more than 200 types of viruses. Ethnobotanical studies and the use traditional experiences have increased the probability of detecting effective medicinal substances for cold by 40%. This study aimed to identify effective medicinal plants for cold in Lorestan province. Traditional medical information of this work was obtained from information from indigenous people in 8 cities of Lorestan province. A previously prepared questionnaire was given to trained health liaisons to record the people's beliefs about the plants. The results showed that 23 medicinal plants were used in Lorestan province for treating cold and its symptoms (cough, sore throat, sneezing, runny nose, etc). Plants studied in this article contained bioactive substances that are recommended as the most popular traditional treatments. More research studies should be done on the efficacy and the potential harms of medicinal plants used by people, and in the case of their positive pharmacological impacts, they can be used to produce natural and effective drugs for cold.
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10.1177/2156587214568458
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pubmed_536_1548
|
This paper summarizes lessons learned from formative research conducted in Bangladesh, Ghana, India, Mali and Nepal to inform the development of newborn health interventions, mostly in the context of field trials. Current practices, constraints to the adoption of optimal practices and implications for implementing inventions to improve newborn survival are discussed for: optimal care during pregnancy; skilled care at birth; optimal delivery and newborn care practices; special care of low birth weight babies; and timely and appropriate care seeking for newborn illness. General lessons concerning target audiences and intervention strategy are also drawn. In brief, interventions to reduce neonatal mortality need to start during pregnancy not only to promote birth preparedness and institutional delivery, but also to start the process of change concerning early newborn care practices. Their target audience should not only be pregnant or recently delivered women, but also include the main gatekeepers, particularly traditional birth attendants, grandmothers and other family members. Health providers' opinions also matter as care practices are less likely to change if families receive conflicting messages from different sources. Interventions are more likely to succeed if they are not simply message based, but include problem solving approaches, and a behavior change component to address community norms. Although antenatal care (ANC) is theoretically a good channel for newborn interventions, capitalising on its potential is not straightforward, and will require considerable investment and intervention development in its own right in order to improve ANC counselling, which will need to extend beyond training and tackle the many working day constraints encountered by ANC providers. Removing or subsidising the cost of deliveries may be a necessary action to increase institutional deliveries, but it is unlikely to be sufficient; measures will need to be put in place to ensure the basic quality of institutional deliveries and newborn care, and to change staff attitudes and practices. Post-natal visits should include observation of the baby, referral and counselling of the mother concerning danger signs in addition to promoting optimal care practices. The lessons learned should guide the development of interventions in other contexts, and ensure that key essential elements are not overlooked. They do not, however, mean that formative research will not be needed in other contexts, although the list of questions to address should be considerably reduced; successful intervention strategies require adaptation to make them local, context-specific if they are to be effective, and ongoing process monitoring to ensure the quality of intervention delivery, to check that it is having its intended effect, and to respond to any concerns from its implementers, recipients or the community. Finally, major gaps in evidence are highlighted. These include: establishing levels of recognition of asphyxiated babies and effectiveness of local solutions for resuscitation; clarifying the extent of the overlap between community perceptions of 'at risk' babies and low birthweight babies; developing and evaluating effective interventions to enable ANC services to deliver effective behaviour change counselling for pregnant and newborn health; evaluating effectiveness of delivering community-based newborn interventions at scale through routine services.
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10.1038/jp.2008.166
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pubmed_973_14077
|
The purpose of this study was to assess, in relation to metabolic control, the cognitive, depressive, and anxiety symptoms among 40 adult patients (age: 18-60 years) with either type 1 (n = 28) or type 2 (n = 12) diabetes mellitus (DM1, DM2). Nineteen healthy subjects matched for age, gender, and education served as the control group. For most cognitive domains, no significant performance differences were found between subjects from the diabetic groups and control subjects. However, diabetes patients demonstrated reduced information processing accuracy along with impaired visual and verbal working memory performance. In addition, psychopathology scores were significantly elevated but did not reach the clinical criteria for depression or anxiety. Overall, there were no significant differences between diabetic subgroups, and no significant correlation was found between cognitive performance, psychopathology scores, and HbA1c values for either subgroup. Thus, patients with DM1 or DM2 may show mild-to-moderate cognitive impairment as well as subtle psychopathological symptoms. While cognitive impairments may be understood in terms of diabetes-associated cognitive dysfunction, psychopathological symptoms may also result from unsuccessful coping with high task demands in everyday life activities. The outcome of the current study underscores the importance of early clinical neuropsychological standardized assessment as well as the diagnosis of cognitive and psychopathological symptoms in adult patients with diabetes.
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10.1080/09084280903526133
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pubmed_795_18021
|
The heme active site structure of chloroperoxidase (CPO), a glycoprotein that displays versatile catalytic activities isolated from the marine mold Caldariomyces fumago, has been characterized by two-dimensional NMR spectroscopic studies. All hyperfine shifted resonances from the heme pocket as well as resonances from catalytically relevant amino acid residues including the heme iron ligand (Cys(29)) attributable to the unique catalytic properties of CPO have been firmly assigned through (a) measurement of nuclear Overhauser effect connectivities, (b) prediction of the Curie intercepts from both one- and two-dimensional variable temperature studies, (c) comparison with assignments made for cyanide derivatives of several well characterized heme proteins such as cytochrome c peroxidase, horseradish peroxidase, and manganese peroxidase, and (d) examination of the crystal structural parameters of CPO. The location of protein modification that differentiates the signatures of the two isozymes of CPO has been postulated. The function of the distal histidine (His(105)) in modulating the catalytic activities of CPO is proposed based on the unique arrangement of this residue within the heme cavity. Contrary to the crystal state, the high affinity Mn(II) binding site in CPO (in solution) is not accessible to externally added Mn(II). The results presented here provide a reasonable explanation for the discrepancies in the literature between spectroscopists and crystallographers concerning the manganese binding site in this unique protein. Our study indicates that results from NMR investigations of the protein in solution can complement the results revealed by x-ray diffraction studies of the crystal form and thus provide a complete and better understanding of the actual structure of the protein.
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10.1074/jbc.M209462200
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pubmed_21_18447
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Class A G protein-coupled receptors (GPCRs) are able to form homodimers and/or oligomeric arrays. We recently proposed, based on bioluminescence resonance energy transfer studies with the M3 muscarinic receptor (M3R), a prototypic class A GPCR, that the M3R is able to form multiple, structurally distinct dimers that are probably transient in nature (McMillin, S. M., Heusel, M., Liu, T., Costanzi, S., and Wess, J. (2011) J. Biol. Chem. 286, 28584-28598). To provide more direct experimental support for this concept, we employed a disulfide cross-linking strategy to trap various M3R dimeric species present in a native lipid environment (transfected COS-7 cells). Disulfide cross-linking studies were carried out with many mutant M3Rs containing single cysteine (Cys) substitutions within two distinct cytoplasmic M3R regions, the C-terminal portion of the second intracellular loop (i2) and helix H8 (H8). The pattern of cross-links that we obtained, in combination with molecular modeling studies, was consistent with the existence of two structurally distinct M3R dimer interfaces, one involving i2/i2 contacts (TM4-TM5-i2 interface) and the other one characterized by H8-H8 interactions (TM1-TM2-H8 interface). Specific H8-H8 disulfide cross-links led to significant impairments in M3R-mediated G protein activation, suggesting that changes in the structural orientation or mobility of H8 are critical for efficient receptor-G protein coupling. Our findings provide novel structural and functional insights into the mechanisms involved in M3R dimerization (oligomerization). Because the M3R shows a high degree of sequence similarity with many other class A GPCRs, our findings should be of considerable general interest.
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10.1074/jbc.M113.503714
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pubmed_57_14538
|
The amplified sensitive detection of protein is essential to biomedical research as well as clinical diagnosis. Here, we developed an ultrasensitive mediator-free triple-enzyme cascade electrocatalytic aptasensor for thrombin detection on the basis of exonuclease-assisted target recycling and hybridization chain reaction (HCR) amplification strategy. The double strands constructed by the hybridization of thrombin binding aptamer (S1) with its complementary strand (S2) were firstly assembled on the electrode. Upon addition of target to the system, the S1 recognized thrombin and left off electrode to make space for assembly of hybrid-primer probe (H0). Then, the H0 triggered the HCR to form the multi-functional hemin/G-quadruplex DNAzyme nanowires. In the mediator-free triple-enzyme cascade electrocatalytic amplification system, the hemin/G-quadruplex DNAzyme nanowires here simultaneously played three roles: the redox probe, NADH oxidase and HRP-mimicking DNAzyme, respectively, which effectively avoided the fussy redox probe and enzyme labeling process, serving a useful alternative or supplement to conventional assays that typically suffer from complexity and poor sensitivity. Additionally, in order to improve the assembly amount of hemin/G-quadruplex DNAzyme nanowire, the exonuclease-assisted target recycling amplification was used for the continuous removal of S1. As a result, the proposed method can detect thrombin specifically with a detection limit as low as 20 fM.
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pubmed_57_14538
|
pubmed_213_15244
|
This article reviews the prevention of hepatitis B virus infection with emphasis on immunoprophylaxis in its 2 forms, passive by the use of immunoglobulins and active by the use of vaccines, plasmatic and recombinant. Both have been shown to be safe, with few secondary effects an highly effective. Response to the vaccine depends on age and immunological status, there are few contraindications. In Venezuela pre-exposure vaccination is recommended taking into account the prevalence of B virus infection, which is high in certain indigenous groups, homosexuals, drug addicts and patients in hemodialysis and intermediate in health workers and pregnant women of low socioeconomic status. Post-exposure vaccination is recommended in sexual contacts of persons infected acutely or chronically with the virus, in newborns of surface antigen positive mothers and in case of accidental percutaneous exposure.
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pubmed_213_15244
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pubmed_323_8657
|
BACKGROUND/PURPOSE
Pilomatricomas, or calcifying epitheliomas of Malherbe, are among the most common superficial cutaneous soft tissue lesions in children. Familiarity with the presenting signs and symptoms allows for the diagnosis to be made on physical examination alone in most patients, avoiding expensive and unnecessary diagnostic imaging.
METHODS
A retrospective IRB-approved review of surgical pathology archives and medical records of all patients undergoing excision of pilomatricomas between 1982 and 2010 was performed to determine the characteristics of the pilomatricoma tumors. Data regarding gender, age, location, size of tumor, and histopathology were collected.
RESULTS
There were 916 pilomatricomas resected in 802 patients. Fifty-five percent of the patients were girls (441 patients). The median age at the time of resection was 6 years (range 5 months to 18 years). Multiple lesions were found in 43 patients (5%). The most common location was head and neck (n = 529, 58%), followed by upper limbs (n = 214, 23%), trunk (n = 130, 14%), and lower limbs (n = 43, 5%). Information on size was available for 674 lesions; mean lesion diameter was 14.0 ± 7.4 mm. Twenty-eight patients (3%) had either recurrent (n = 11) or metachronous (n = 17) lesions resected at our institution, with a median interval of 12 months after initial resection (range 5 weeks to 5 years). No cases of pilomatrix carcinoma were observed.
CONCLUSION
The majority of pilomatricomas occur in the head and neck, although they can present in any location. Approximately 5% of children have multiple lesions. Pilomatricomas occur slightly more commonly in girls, and 66% of lesions occur in children < 10 years of age. Complete surgical excision is necessary to prevent recurrence. Recurrences and pilomatrix carcinoma are very rare if complete excision is achieved.
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pubmed_323_8657
|
pubmed_137_10894
|
Mesenchymal stem cells (MSCs) undergo self-renewal and differentiation into multiple lineages. They exert anti-inflammatory and immunomodulatory effects via either cell-cell contact or via the production of soluble factors. Various anti-inflammatory and immunomodulatory mechanisms have been identified using experimental murine MSCs. The most representative mechanism is the induction of FOXP3+ regulatory T cells (Treg cells) via the production of transforming growth factor (TGF)-β, which has also been reported in human MSCs. Recent studies have demonstrated that insulin-like growth factor (IGF) is also involved in the induction of FOXP3+ Treg cells. We previously demonstrated that the induction of FOXP3+ Treg cells by IGF is suppressed by the expression of IGF-binding protein-4 (IGFBP-4), which is an inhibitor of IGF. Because human MSCs produce both IGFs and IGFBP4, they may be considered to maintain immunological homeostasis by positive regulation of Treg cells through the production of growth factors as well as by a negative regulatory mechanism. Although human MSCs have already been applied in regenerative therapy and autoimmune disease treatment, control of their positive and negative regulatory mechanisms is expected to lead to more efficient clinical applications.
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10.1615/CritRevImmunol.2018027821
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pubmed_373_19346
|
The role of sucrose cleavage in determining sink strength in potato was investigated by generating transgenic potato plants that expressed a yeast invertase in either the cytosol or apoplast of tubers. Cytosolic localization gave rise to a reduction in tuber size and an increase in tuber number per plant whereas apoplastic targeting led to an increase in tuber size and a decrease in tuber number per plant. Sink organ size can be manipulated through modification of sucrose metabolism.
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10.1038/nbt0897-794
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pubmed_686_17137
|
OBJECTIVE
To investigate the possibility of reconstruction of dentin-pulp complex by tissue engineering technology.
METHODS
Rat dental pulp stem cells were seeded into HA-TCP scaffold and incubated for 20 hours in vitro. Then the cell-scaffold complex was implanted subcutaneously into the dorsal side of nude mice. 8 weeks postimplantation, the samples were extracted for histological and immunohistochemical examinations.
RESULTS
Three strata of tissue were observed in the hole of HA-TCP scaffold. They were dentin-like tissue, predentin-like tissue and pulp-like tissue respectively from the inner surface of the pore to the center. Dentin tubules were obvious in predentin-like and dentin-like tissue lining from the pulp-like tissue through predentin-like tissue and dentin-like tissue. Cells localized along the edge of pulp-like tissue were dense and polarized, resembling odontoblasts. Immunohistochemical study demonstrated DSP and DMP1 expression in these odontoblast-like cells and in the area of predentin-like tissue.
CONCLUSIONS
Tissue-engineered rat dentin-pulp complex was reconstructed by seeding HA-TCP scaffold with rat dental pulp stem cells.
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pubmed_686_17137
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pubmed_931_18990
|
Lipomembranous changes are histological findings without specific clinical correlations, and are thought to be related to vascular impairment in fatty tissue. We describe a case of systemic lupus erythematosus (SLE) in which subcutaneous induration of the lower leg showed lipomembranous changes and calcification. This patient showed thrombophilia with thrombosis of the femoral and iliac veins, and cerebellar and myocardial infarction. A biopsy specimen from the subcutaneous tissue surrounding the multiple leg ulcers revealed degeneration of fat cells, lipomembranous changes in the fatty tissues, and calcification. Another biopsy specimen from the outer edges of the ulcers showed microthrombi and fibrinoid changes in the vessel walls, and mononuclear cell infiltrates in the dermis. Lipomembranous changes have been seen in connective tissue disorders such as lupus profundus, morphoea, systemic sclerosis, and panniculitis associated with dermatomyositis, but rarely associated with SLE. We speculate that ischaemic changes due to the vascular disturbance of the lower legs may have induced lipomembranous changes and calcification in the subcutaneous tissues in the present case.
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10.1111/j.1365-2230.2007.02358.x
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pubmed_257_8719
|
Nineteen patients with advanced cancer for which there was no effective standard therapy or whose disease was refractory to standard therapy were treated with recombinant tumor necrosis factor (rTNF). The rTNF was administered subcutaneously for 5 consecutive days every other week for 3 treatment weeks. The doses administered ranged from 5 micrograms/m2/day to 150 micrograms/m2/day. There was no intrapatient dose escalation. Systemic side effects of chills, fever, hypotension, nausea, vomiting, and headache were mild and self-limiting. At the maximum tolerated dose of 150 micrograms/m2/day, five of seven patients experienced moderate to severe thrombocytopenia. Mild rapid declines in total leukocyte count occurred within 60-90 min of administration of the drug, followed by a rise in the total leukocyte count by 120 min. When the total daily dose was administered in a single subcutaneous site, skin ulceration and necrosis occurred at the 100 micrograms/m2/day dose. By giving the total daily dose in two subcutaneous sites, the maximum tolerated dose increased to 150 micrograms/m2/day, and there was no further skin ulceration or necrosis. Skin necrosis occurred in the abdomen and thigh but not on the upper extremity at the 100 micrograms/m2/day dose given in a single site. There was no other significant organ toxicity. No rTNF was detectable in the serum even at the highest doses. No antibodies to TNF developed in any of the patients. The recommended dose of rTNF for Phase II trials given for 5 days subcutaneously is 150 micrograms/m2/day divided into two or more sites.
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pubmed_257_8719
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pubmed_1073_21065
|
We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to "polymer nano-aggregate" particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers.
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pubmed_1073_21065
|
pubmed_751_9492
|
Serological typing of P. aeruginosa is the most simple and reliable procedure recommended for "in-house" investigations and for studies of suspected outbreaks of infection by this microorganism. It is also a useful procedure in order to know serotype prevalence in a definite geographical area and to obtain indications about the more appropriate composition of polyvalent anti-Pseudomonas vaccines. In the present report, we describe the relatively high frequency of isolation of serogroup 12 from patients in Palermo, Italy. Serogroup 12 is very rare in north-Europe and in the USA, and, as a consequence, it is not included in some vaccine preparations. In Palermo, strains belonging to this serogroup, resistant to a large number of antibiotics, were on the contrary isolated, during more than six years, in different hospitals and from three out-patients. In a Burns Unit, they were in particular responsible for extensive and life-threatening outbreaks.
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10.1007/BF00141801
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pubmed_256_17068
|
BACKGROUND
The high frequency of relapse after induction chemotherapy of advanced ovarian carcinoma calls for new therapeutic approaches. Lysis of ovarian carcinoma cells can be achieved by retargeting of T lymphocytes using F(ab')2 fragments of the bispecific monoclonal antibody (MAb) OC/TR, which is directed to the CD3 molecule on T lymphocytes and to the folate receptor on ovarian carcinoma cells.
PURPOSE
Our purpose was to assess in ovarian carcinoma patients the antitumor activity of in vitro-activated autologous peripheral blood T lymphocytes retargeted with OC/TR.
METHODS
Patients with epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages III and IV) meeting specific criteria were eligible to enter a phase II immunotherapy trial. Before immunotherapy, the 28 patients who entered the trial underwent laparotomy to reduce their tumor load and to allow measurement of all indicator lesions. They then received two cycles of five daily intraperitoneal infusions of autologous in vitro activated peripheral blood T lymphocytes retargeted with OC/TR plus recombinant interleukin 2 (IL-2) with (n = 11) or without (n = 17) a second daily infusion of OC/TR F(ab')2 and IL-2. Response to treatment could be assessed in 26 patients following explorative laparotomy; time to progression could be assessed in 27 patients.
RESULTS
Seven patients had clinical evidence of progressive disease after treatment and therefore did not undergo laparotomy. Of the 19 patients evaluated by surgery and histology, three showed complete response, one showed complete intraperitoneal response with progressive disease in retroperitoneal lymph nodes, three showed partial response, seven had stable disease, and five had progressive disease. The overall intraperitoneal response rate was 27% (95% confidence interval [CI] = 10%-44%). The complete responses seen in three patients lasted 26 months in one patient, 23 months in the second, and 18 months in the third. Two patients were not assessable for response. One of these patients had bowel perforation during catheter removal, which precluded further evaluation. The second patient was positive only by cytologic examination before immunotherapy, was tumor free at laparotomy after immunotherapy, and remained so for the entire 21 months of follow-up, as determined by cytologic examination of random biopsy specimens. The median time to disease progression in the 15 assessable patients plus those who had stable disease was 11 months (95% CI = 6-18 months). Immunotherapy-related toxic effects included mild to moderate fever, nausea, emesis, and fatigue. Anti-mouse antibodies were detectable by the end of the treatment in 21 of 25 patients tested.
CONCLUSIONS
Locoregional immunotherapy of ovarian cancer with bispecific MAb-retargeted T lymphocytes can result in tumor regression. Toxicity was mild to moderate and only transient.
IMPLICATIONS
Improvement in systemic antitumor responses is needed before this approach can prove useful as adjunctive treatment following induction chemotherapy in patients with minimal residual disease.
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10.1093/jnci/87.19.1463
|
pubmed_130_3023
|
PURPOSE
In this multicenter phase 3 trial, the efficacy and safety of 60 Gy and 50 Gy doses delivered with modern radiotherapy technology for definitive concurrent chemoradiotherapy (CCRT) in patients with inoperable esophageal squamous cell carcinoma (ESCC) were evaluated.
PATIENTS AND METHODS
Patients with pathologically confirmed stage IIA‒IVA ESCC were randomized 1:1 to receive conventional fractionated 60 Gy or 50 Gy to the tumor and regional lymph nodes. Concurrent weekly chemotherapy (docetaxel 25 mg/m2; cisplatin 25 mg/m2) and two cycles of consolidation chemotherapy (docetaxel 70 mg/m2; cisplatin 25 mg/m2 days 1‒3) were administered.
RESULTS
A total of 319 patients were analyzed for survival, and the median follow-up was 34.0 months. The 1- and 3-year locoregional progression-free survival (PFS) rates for the 60 Gy group were 75.6% and 49.5% versus 72.1% and 48.4%, respectively, for the 50 Gy group [HR, 1.00; 95% confidence interval (CI), 0.75‒1.35; P = 0.98]. The overall survival rates were 83.7% and 53.1% versus 84.8% and 52.7%, respectively (HR, 0.99; 95% CI, 0.73‒1.35; P = 0.96), whereas the PFS rates were 71.2% and 46.4% versus 65.2% and 46.1%, respectively (HR, 0.97; 95% CI, 0.73‒1.30; P = 0.86). The incidence of grade 3+ radiotherapy pneumonitis was higher in the 60 Gy group (nominal P = 0.03) than in the 50 Gy group.
CONCLUSIONS
The 60 Gy arm had similar survival endpoints but a higher severe pneumonitis rate compared with the 50 Gy arm. Fifty Gy should be considered as the recommended dose in CCRT for ESCC.
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10.1158/1078-0432.CCR-21-3843
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pubmed_54_1648
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Positron-acoustic (PA) solitary waves (SWs) and double layers (DLs) in four-component plasmas consisting of immobile positive ions, mobile cold positrons, and superthermal (kappa distributed) hot positrons and electrons are investigated both numerically and analytically by deriving Korteweg-de Vries (K-dV), modified K-dV (mK-dV), and Gardner equations along with their DLs solutions using the reductive perturbation method. It is examined that depending on the plasma parameters, the K-dV SWs, Gardner SWs, and DLs support either compressive or rarefactive structures, whereas mK-dV SWs support only compressive structure. It is also found that the presence of superthermal (kappa distributed) hot positrons and hot electrons significantly modify the basic features of PA SWs as well as PA DLs. Besides, the critical number density ratio of hot positrons and cold positrons play an important role in the polarity of PA SWs and DLs. The implications of our results in different space as well as laboratory plasma environments are briefly discussed.
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10.1063/1.4895049
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pubmed_240_11356
|
This year's analysis of discontinued drugs in oncology reveals that the trend of increasing numbers of candidate drug development terminations seen in recent years has continued into 2011. Thirty-seven drugs were dropped from the global oncology development pipeline in 2011, significantly more than the 28 discontinuations reported in 2010. Of note were the number of terminations reported for strategic reasons and the striking number of drugs (23) discontinued in or at the end of Phase I development. This article provides a summary of those drugs discontinued in 2011 and discusses the observations in the context of the rapid changes occurring in the way new anticancer drugs are developed.
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10.1517/13543784.2013.739605
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pubmed_226_19658
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Limb-girdle muscular dystrophy R3, a rare genetic disorder affecting the limb proximal muscles, is caused by mutations in the α-sarcoglycan gene (Sgca) and aggravated by an immune-mediated damage, finely modulated by the extracellular (e)ATP/purinoceptors axis. Currently, no specific drugs are available. The aim of this study was to evaluate the therapeutic effectiveness of a selective P2X7 purinoreceptor antagonist, A438079. Sgca knockout mice were treated with A438079 every two days at 3 mg/Kg for 24 weeks. The P2X7 antagonist improved clinical parameters by ameliorating mice motor function and decreasing serum creatine kinase levels. Histological analysis of muscle morphology indicated a significant reduction of the percentage of central nuclei, of fiber size variability and of the extent of local fibrosis and inflammation. A cytometric characterization of the muscle inflammatory infiltrates showed that A438079 significantly decreased innate immune cells and upregulated the immunosuppressive regulatory T cell subpopulation. In α-sarcoglycan null mice, the selective P2X7 antagonist A438079 has been shown to be effective to counteract the progression of the dystrophic phenotype and to reduce the inflammatory response. P2X7 antagonism via selective inhibitors could be included in the immunosuppressant strategies aimed to dampen the basal immune-mediated damage and to favor a better engraftment of gene-cell therapies.
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10.3390/ph15010089
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pubmed_1142_3709
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We present PhenCards ( https://phencards.org ), a database and web server intended as a one-stop shop for previously disconnected biomedical knowledge related to human clinical phenotypes. Users can query human phenotype terms or clinical notes. PhenCards obtains relevant disease/phenotype prevalence and co-occurrence, drug, procedural, pathway, literature, grant, and collaborator data. PhenCards recommends the most probable genetic diseases and candidate genes based on phenotype terms from clinical notes. PhenCards facilitates exploration of phenotype, e.g., which drugs cause or are prescribed for patient symptoms, which genes likely cause specific symptoms, and which comorbidities co-occur with phenotypes.
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10.1186/s13073-021-00909-8
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pubmed_596_12717
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Toxoplasma gondii is a protozoan parasite that causes severe diseases in mammals, including humans, around the world. In China, pork is the main meat source; accordingly, T. gondii in pigs is considered an important source for human toxoplasmosis. Understanding the epidemiology of toxoplasmosis in pig farms is thus important for control of the disease in humans. The purpose of the present study was to investigate the epizootiology of T. gondii infections in pig farms in central China by assessing the seroprevalence and risk factors of this disease. In the present study, 3,558 sera samples were collected from pigs in 37 large-scale pig farms in this region and tested by AG-ELISA. The total seroprevalence was 24.5%, with the greatest prevalence in breeding pigs. The risk factors for toxoplasmosis suggest that high frequency of the contact of pigs with cats (P ≤ 0.01; IC 95%), high density of pig breeding (P ≤ 0.01; IC 95%), the presence of mosquitoes and flies (P ≤ 0.01; IC 95%), semi-patency pens (P ≤ 0.05; IC 95%), and low frequency of scavenging (P ≤ 0.01; IC 95%) were all associated with seroprevalence. In addition, the use of sulfonamides (P ≤ 0.01; IC 95%) significantly decreased seroprevalence. This is the first report of anti- T. gondii antibodies in pigs on large-scale pig farms in central China. The findings will provide useful information for designing control strategies of toxoplasmasis in pig farms.
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10.1645/GE-2646.1
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pubmed_1048_12649
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The L-arabinose-inducible araBAD promoter (PBAD) allows tightly controlled and tunable expression of genes of interest in a broad range of bacterial species. It has been successfully used to study bacterial sRNA regulation, where PBAD drives expression of target mRNA translational fusions. Here we report that in Escherichia coli, Spot 42 sRNA can regulate PBAD promoter activity by affecting arabinose uptake. We demonstrate that Spot 42 sRNA represses araF, a gene encoding the AraF subunit of the high-affinity low-capacity arabinose transporter AraFGH, through direct base pairing interactions. We further show that endogenous Spot 42 sRNA is sufficient to repress araF expression under various growth conditions. Finally, we demonstrate this posttranscriptional repression has a biological consequence, decreasing the induction of PBAD at low levels of arabinose. This problem can be circumvented using strategies reported previously for avoiding all-or-none induction behavior, that is through constitutive expression of the low-affinity high-capacity arabinose transporter AraE or induction with higher concentration of inducers. This work adds araF to the set of Spot 42-regulated genes, in agreement with previous studies suggesting that Spot 42, itself negatively regulated by cAMP-CRP complex, reinforces the catabolite repression network.
IMPORTANCE
The bacterial arabinose inducible system is widely used for titratable control of gene expression. We demonstrate here that a post-transcriptional mechanism mediated by the Spot 42 sRNA contributes to the functionality of the PBAD system at subsaturating inducer concentrations by affecting inducer uptake. Our finding extends the inputs into the known transcriptional control for the PBAD system, and has implications for improving its usage for tunable gene expression.
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10.1128/JB.00691-16
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pubmed_1103_13547
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Noninflammatory monocyte macrophages use alphavbeta3 integrin to selectively bind apoptotic cells, initiating their phagocytic removal. In a related process, the retinal pigment epithelium (RPE) employs alphavbeta5 integrin to recognize spent photoreceptor outer segment particles (OS). Here, we show that apoptotic cells and OS compete for binding to these receptors, indicating that OS and apoptotic cells expose surface signals recognizable by alphavbeta3 and alphavbeta5. Particle binding to alphavbeta5 required protein kinase C (PKC) activation. In RPE, alphavbeta5 binding was maximally activated even before any phagocytic challenge and was reduced by PKC inhibitors. In macrophages, it was dormant but became activated upon PKC stimulation. PKC-activated alphavbeta5-mediated binding in macrophages differed from constitutive binding to the same integrin receptor in RPE cells in that the former followed much faster kinetics, similar to particle binding mediated by alphavbeta3. Activation of alphavbeta5 for particle binding correlated with its recruitment into a detergent-insoluble fraction, a process sensitive to pharmacological modulation of PKC in both types of phagocytes. Furthermore, alphavbeta5 but not alphavbeta3 particle binding required actin microfilaments. These data constitute the first evidence that noninflammatory phagocytes actively regulate the earliest phase of phagocytic clearance, particle binding, by controlling receptor activity.
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10.1084/jem.190.6.861
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pubmed_725_95
|
Eleven patients with histologically proven cholangiocarcinoma and gallbladder carcinoma were treated with hepatic artery infusion (HAI) of 5-fluorouracil (5-FU) and mitomycin C (Mito-C). Catheters were placed percutaneously through the femoral artery. The schedule used was 5-FU 1200/mg/m2/day given as a continuous infusion for 4 days, plus Mito-C 6 mg/m2 on days 1 and 4. Courses were repeated every 4 weeks. Complete responses (CR) occurred in one patient (9%), and partial response (PR) occurred in six patients (55%). Median survival for all patients from the start of the first treatment was 12.5+ months. Median duration of the response was 3.0 months. Median survival of the patients with gallbladder carcinoma was 12.5 months, and for patients with cholangiocarcinoma has not yet been reached. Drug toxicity was mild, and morbidity of the HAI was minimal. Further trials of chemotherapy in these two neoplasms are warranted.
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10.1002/1097-0142(19841015)54:8<1513::aid-cncr2820540806>3.0.co;2-9
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pubmed_984_14986
|
OBJECTIVES
Cholesterol has been linked to Alzheimer's disease (AD) and plasma 24S-hydroxycholesterol (24OHC) has been suggested as a surrogate marker for brain cholesterol metabolism. This study investigates the relation of 24OHC as well as markers of extracerebral cholesterol homeostasis (lanosterol, lathosterol, cholesterol, LDL-C, HDL-C and 27-hydroxycholesterol) with brain volumes in memory clinic patients.
METHODS
96 patients (33 with subjective cognitive impairment--SCI; 36 with mild cognitive impairment--MCI; 27 with AD) referred to the Memory Clinic at Karolinska University Hospital, Sweden. Plasma assessments were done by isotope dilution-mass spectrometry. MRI measurements were done using custom-made software BMAP (imaging laboratory, Karolinska Institutet), running on HERMES platform.
RESULTS
Ratios of 24-hydroxycholesterol, 27-hydroxycholesterol, lanosterol and lathosterol to cholesterol (R_24OHC, R_27OHC, R_lanosterol and R_lathosterol) were significantly lower in patients with AD. In the whole population, after controlling for age, sex, APOE genotype and statins, R_24OHC was positively related to gray matter (GM) fraction. However, when groups were considered separately, the relation to GM volume, GM and parenchymal fractions was significant in the SCI group only (p<0.05). There was a significant positive association between cholesterol and white matter (WM) volume, WM and parenchymal fractions in patients with AD.
CONCLUSIONS
Plasma R_24OHC was lower in patients with AD, but R_24OHC was significantly related to brain volumes in the control group only. One reason may be the previously demonstrated abnormal expression of cholesterol 24S-hydroxylase in astrocytes in AD, which may limit the usefulness of this plasma marker in this specific disease. The findings on cholesterol agree with previous reports of decreasing plasma cholesterol levels in AD patients, suggesting a CNS-mediated effect on extracerebral cholesterol homeostasis.
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10.1016/j.neulet.2009.06.073
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pubmed_1086_11694
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The use of dedicated bus shoulders is a key method for implementing bus rapid transit (BRT) in areas that do not have the space for additional infrastructure. However, the narrow width of the bus shoulder and the need to anticipate traffic hazards in the adjacent lane can both be significant stressors for bus drivers. Bus driver mental workload and stress in response to these conditions should be a significant concern both for operational safety and driver health. This pilot study evaluated the potential stressors of traffic density and shoulder width in the context of an express BRT service in a large US metropolitan area. In addition, the study considered the potential role of a prototype lane support system (LSS) to support vehicle control within the narrow shoulder boundaries. Ten experienced bus drivers drove an actual route with an instrumented bus equipped with and without LSS. Self-reported effort was recorded along with performance measures of speed and position control relevant to mobility and safety objectives. Bus drivers did note stressors in the BRT environment and the prototype LSS. However, the use of the shoulder during high-density traffic conditions did improve mobility. Moreover, the LSS did enhance safety on the shoulder when there was high-density traffic in the adjacent lane. However, there was no evidence that the LSS reduced bus driver workload while operating in the narrow shoulder. Future research should consider the impact of BRT operations and support systems on bus driver mental workload and stress, and support the deployment of such devices for bus operations on shoulders during high traffic volumes.
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10.1080/00140130600577544
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pubmed_412_12833
|
OBJECTIVE
To investigate possible associations between use of cardiovascular drugs and suicide.
DESIGN
Cross sectional ecological study based on rates of use of eight cardiovascular drug groups by outpatients. A population based cohort study including users of drugs to control hypertension.
SUBJECTS
The ecological study included 152 of Sweden's 284 municipalities. The cohort study included all inhabitants of one Swedish municipality who during 1988 or 1989 had purchased cardiovascular agents from pharmacies within the municipality. Six hundred and seventeen subjects (18.2%) were classified as users of calcium channel blockers and 2780 (81.8%) as non-users.
MAIN OUTCOME MEASURES
Partial correlations (least squares method) between rates of use of cardiovascular drugs and age standardised mortality from suicide in Swedish municipalities. Hazard ratios for risk of suicide with adjustments for difference in age and sex in users of calcium channel blockers compared with users of other hypertensive drugs.
RESULTS
Among the Swedish municipalities the use of each cardiovascular drug group except angiotensin converting enzyme inhibitors correlated significantly and positively with suicide rates. After adjustment for the use of other cardiovascular drug groups, as a substitute for the prevalence of cardiovascular morbidity, only the correlation with calcium channel blockers remained significant (r = 0.29, P < 0.001). In the cohort study, five users and four non-users of calcium channel blockers committed suicide during the follow up until the end of 1994. The absolute risk associated with use of calcium channel blockers was 1.1 suicides per 1000 person years. The relative risk, adjusted for differences in age and sex, among users versus non-users was 5.4 (95% confidence interval 1.4 to 20.5).
CONCLUSIONS
Use of calcium channel blockers may increase the risk of suicide.
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10.1136/bmj.316.7133.741
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pubmed_271_6108
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The Rickettsiales Ehrlichia ruminantium (ER) is the causative agent of heartwater, a fatal tick-borne disease of livestock in sub-Saharan Africa and in the Caribbean, posing strong economical constraints to livestock production. In an attempt to identify the most prominent proteins expressed by this bacterium, especially those encoded by the major antigenic protein 1 (map1) multigene family, a proteome map of ER cultivated in endothelial cells was constructed by using two dimensional gel electrophoresis combined with mass spectrometry. Among the sixty-four spots detected, we could identify only four proteins from the MAP1-family; the other proteins detected were mainly related to energy, amino acid and general metabolism (26%), to protein turnover, chaperones and survival (21%) and to information processes (14%) or classified as hypothetical proteins (23%). Additional studies on MAP1-family protein using immunochemical labeling also revealed that these proteins are differentially expressed along the bacterium life cycle, presenting different structural organization. Interestingly, when infectious elementary bodies (EBs) are released from host cells, MAP1 appears to be organized in SDS and heat-resistant dimers and trimers stabilized by disulfide bridges. Overall, the results presented herein not only reveal the first partial proteome map of ER but provide new insights on the expression ER MAP1-family proteins in host endothelial cells.
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10.1016/j.vetmic.2011.11.022
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pubmed_160_6994
|
In the current study Ibuprofen was embedded in a methacrylate copolymer (Eudragit® EPO) matrix to produce solid dispersions by hot-melt extrusion (HME) processing. The obtained granules were incorporated in orally disintegrating tablets (ODTs). The tablets were developed by varying the ratio of superdisintegrants such as sodium croscarmellose and crosslinked polyvinylpyrrolidone grades while a direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets which included porosity, hardness, friability and dissolution profiles were further evaluated and compared with Nurofen® Meltlet ODTs. The taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and improved tablet palatability.
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10.1016/j.colsurfb.2011.04.007
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pubmed_217_21990
|
BACKGROUND
Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist).
OBJECTIVES
The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including cytisine, dianicline and varenicline for smoking cessation.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, PsycINFO and Web of Science using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in December 2011. We also searched online clinical trials registers.
SELECTION CRITERIA
We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment.
DATA COLLECTION AND ANALYSIS
We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model.
MAIN RESULTS
Two recent cytisine trials (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled RR of 3.98 (95% confidence interval (CI) 2.01 to 7.87). One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). Fifteen trials compared varenicline with placebo for smoking cessation; three of these also included a bupropion treatment arm. We also found one open-label trial comparing varenicline plus counselling with counselling alone. We found one relapse prevention trial, comparing varenicline with placebo, and two open-label trials comparing varenicline with nicotine replacement therapy (NRT). We also include one trial in which all the participants were given varenicline, but received behavioural support either online or by phone calls, or by both methods. This trial is not included in the analyses, but contributes to the data on safety and tolerability. The included studies covered 12,223 participants, 8100 of whom used varenicline.The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.27 (95% CI 2.02 to 2.55; 14 trials, 6166 people, excluding one trial evaluating long term safety). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.09 (95% CI 1.56 to 2.78; 4 trials, 1272 people). The pooled RR for varenicline versus bupropion at one year was 1.52 (95% CI 1.22 to 1.88; 3 trials, 1622 people). The RR for varenicline versus NRT for point prevalence abstinence at 24 weeks was 1.13 (95% CI 0.94 to 1.35; 2 trials, 778 people). The two trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The main adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. A meta-analysis of reported serious adverse events occurring during or after active treatment and not necessarily considered attributable to treatment suggests there may be a one-third increase in the chance of severe adverse effects among people using varenicline (RR 1.36; 95% CI 1.04 to 1.79; 17 trials, 7725 people), but this finding needs to be tested further. Post-marketing safety data have raised questions about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation. The labelling of varenicline was amended in 2008, and the manufacturers produced a Medication Guide. Thus far, surveillance reports and secondary analyses of trial data are inconclusive, but the possibility of a link between varenicline and serious psychiatric or cardiovascular events cannot be ruled out.
AUTHORS' CONCLUSIONS
Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out.Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.
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10.1002/14651858.CD006103.pub6
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pubmed_446_25030
|
BACKGROUND
Loss to follow-up, if related to exposures, confounders and outcomes of interest, may bias association estimates. We estimated the magnitude and direction of such bias in a prospective cohort study of crash injury among cyclists.
METHODS
The Taupo Bicycle Study involved 2590 adult cyclists recruited from New Zealand's largest cycling event in 2006 and followed over a median period of 4.6 years through linkage to four administrative databases. We resurveyed the participants in 2009 and excluded three participants who died prior to the resurvey. We compared baseline characteristics and crash outcomes of the baseline (2006) and follow-up (those who responded in 2009) cohorts by ratios of relative frequencies and estimated potential bias from loss to follow-up on seven exposure-outcome associations of interest by ratios of HRs.
RESULTS
Of the 2587 cyclists in the baseline cohort, 1526 (60%) responded to the follow-up survey. The responders were older, more educated and more socioeconomically advantaged. They were more experienced cyclists who often rode in a bunch, off-road or in the dark, but were less likely to engage in other risky cycling behaviours. Additionally, they experienced bicycle crashes more frequently during follow-up. The selection bias ranged between -10% and +9% for selected associations.
CONCLUSIONS
Loss to follow-up was differential by demographic, cycling and behavioural risk characteristics as well as crash outcomes, but did not substantially bias association estimates of primary research interest.
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10.1136/injuryprev-2013-040997
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pubmed_397_11181
|
The evaluation of liver injury in HIV patients co-infected with HBV and HCV should follow the same principles as the evaluation of any patient with chronic liver disease. The initial clinical evaluation should include documentation of risk factors for progressive disease. HIV history is important particularly with respect to a past history of significant or prolonged immunosuppression as this has been clinically correlated with more advanced liver disease. Liver transaminases are an important predictor of disease severity and progression in HIV patients. Liver biopsy has remained the 'gold standard' for the grading of inflammation and staging of disease. We would still recommend liver biopsy in HIV patients particularly those with HCV because recent community-based studies in the HAART era have suggested slower rates of progression for HIV/HCV than studies from tertiary care centres and older cohorts. Since, liver biopsy is invasive and expensive, non-invasive techniques including serological tests and novel imaging techniques have evolved to stage liver fibrosis. A novel technique for measuring hepatic elasticity has recently been validated alone and in combination with serum markers for HCV mono-infection. Future trends for staging liver disease must not only focus on cross sectional diagnosis but on utilizing novel techniques to stratify risk for disease progression over time.
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10.1016/j.jhep.2005.11.026
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pubmed_1050_5683
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Wettability control of carbonates is a central concept for enhanced petroleum recovery, but a mechanistic understanding of the associated molecular-scale chemical processes remains unclear. We directly probe the interface of calcium carbonate (calcite) with natural petroleum oil, synthetic petroleum analogues, and aqueous brines to understand the molecular scale behavior at this interface. The calcite-petroleum interface structure is similar whether or not calcite was previously exposed to an aqueous brine, and is characterized by an adsorbed interfacial layer, significant structural changes within the calcite surface, and increased surface roughness. No evidence for an often-assumed thin-brine wetting layer at the calcite-petroleum interface is observed. These features differ from those observed at the calcite-brine interface, and for parallel measurements using model synthetic petroleum mixtures (consisting of representative components, including dodecane, toluene, and asphaltene). Changes to the interface after petroleum displacement by aqueous brines are also discussed.
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10.1038/s41598-020-77393-4
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pubmed_781_16077
|
BACKGROUND AND STUDY AIMS
The management of patients with colon polyps who are referred to surgery remains uncharacterized in a population-based setting. The aims of this study were to determine the frequency, risk factors, and outcomes of patients referred for surgical resection of colorectal polyps.
PATIENTS AND METHODS
All patients who underwent a colonoscopy for positive fecal occult blood test in the setting of a population-based colorectal cancer screening program in France between 2003 and 2012 were analyzed. The primary outcome was the proportion of patients undergoing colorectal surgery for polyps without invasive carcinoma. Logistic regression analysis was applied to identify risk factors for surgical resection.
RESULTS
Among 4251 patients with at least one colorectal polyp, 175 (4.1 %) underwent colorectal surgery. Risk factors for surgery included size, proximal polyp location, advanced histology (villous or high grade dysplasia), the endoscopy center, and colonoscopy performed during the first half of the study period. Subgroup analysis of 3475 colonoscopies performed by 22 endoscopists who performed at least 50 colonoscopies during the study period, identified the endoscopist as an additional risk factor. The adjusted proportions of referrals to surgery ranged from 0 to 46.6 % per endoscopist for polyps ≥ 20 mm (median 20.2 %). Overall, surgical complications occurred in 24.0 %, and one patient died following surgery (0.5 %). None of the 175 patients who underwent surgery were referred to a tertiary endoscopic center prior to surgery.
CONCLUSIONS
In this population-based study, 4.1 % of patients with nonmalignant polyps were referred for surgical resection. The endoscopist was one important factor that was associated with surgical referral. To further decrease the proportion of inappropriate surgery in patients, endoscopists should refer their patients with large or difficult polyps to expert endoscopists prior to surgery.
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10.1055/s-0034-1392976
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pubmed_449_7142
|
The authors report on a case of sacral agenesis evaluated by Computed Tomography (CT) of the spine. Sacral agenesis is an exceedingly rare, nongenetic, developmental anomaly which consists in an absence of the entire sacrococcygeal complex. Although maternal diabetes appears to be the most important etiologic factor, the significant teratogenetic effects related to maternal diabetes are not yet completely understood. Only few cases have been reported in neurological and neurosurgical literature because most authors believe that the neurological deficits associated with sacral agenesis are static and, therefore, myelography and surgical approach are useless. However, sacral agenesis can be surgically treated when dural sac stenosis is evident in presence of progressive neurological deficits. The usefulness of CT in depicting nervous anomalies which may favorably respond to surgical treatment is emphasized, in particular when compared with contrast myelography. CT scan seems able to replace contrast myelography in delineating the intraspinal nervous anomalies, thus avoiding the myelographic risks.
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pubmed_449_7142
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pubmed_337_5237
|
What do quantum cellular automata (QCA), "on water" reactions, and SN 1-type organocatalytic transformations have in common? The link between these distant arguments is the practical access to useful intermediates and key products through the use of stabilized carbenium ions. Over 10 years, starting with a carbenium ion bearing a ferrocenyl group, to the 1,3-benzodithiolylium carbenium ion, our group has exploited the use of these intermediates in useful and practical synthetic transformations. In particular, we have applied the use of carbenium ions to stereoselective organocatalytic alkylation reactions, showing a possible solution for the "holy grail of organocatalysis". Examples of the use of these quite stabilized intermediates are now also considered in organometallic chemistry. On the other hand, the stable carbenium ions are also applied to tailored molecules adapted to quantum cellular automata, a new possible paradigm for computation. Carbenium ions are not a problem, they can be a/the solution!
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10.1002/tcr.201500299
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pubmed_241_7522
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OBJECTIVE
Thymidine reverse transcriptase inhibitors (tNRTI) are strong inhibitors of PPAR-gamma and clearly implicated as a cause of lipoatrophy. Thiazolidenediaones (TZD), potent PPAR-gamma agonists, would be expected to be beneficial in HIV lipoatrophy, but prior studies have been conflicting. None specifically excluded the use of tNRTIs. We report the first study in individuals treated with tNRTI-sparing regimens using a TZD for treatment of HIV lipoatrophy.
DESIGN
This double-blind, placebo-controlled study evaluated limb fat in HIV-infected individuals with lipoatrophy who discontinued tNRTI at least 24 weeks prior to enrollment.
METHODS
Individuals were randomized to rosiglitazone vs. placebo for 48 weeks. Dual energy X-ray absorptiometry (DEXA)-scans and fasting metabolic assessments were serially performed.
RESULTS
We enrolled 71 individuals, 17% were female and 51% white. Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group (P = 0.04). At 48 weeks, limb fat (grams) increased significantly (P = 0.02) more in the rosiglitazone than in the placebo group: median (IQR) 448 (138, 1670) vs. 153 (-100, 682), respectively. Of lipids parameters, only total cholesterol increased significantly more in the rosiglitazone group (P = 0.008). Prevalence of metabolic syndrome and total bone mineral density did not change between or within groups.
CONCLUSION
In the absence of tNRTI, rosiglitazone significantly improves lipoatrophy without deleterious effect on bone mineral density. Total cholesterol, but not triglycerides, significantly increased in the rosiglitazone arm. The glitazones may be a promising addition for accelerating fat recovery in individuals who had switched off tNRTI and remain with significant lipoatrophy.
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10.1097/QAD.0b013e328339e274
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pubmed_110_3443
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Mean responses and fluctuations of accommodation were recorded by means of a high-sensitivity infra-red optometer over a large dioptric range (+3 to -9 D). We found that both the effective absolute amplitude and the 2 Hz relative activity of fluctuations of accommodation exhibit a maximum within the -1 to -4 D range of stimulus vergence for which the focus error (lag of accommodation) is minimal, whereas no activity is observed at the subject's near and far points. But the 2 Hz relative activity of accommodative fluctuations provides a better description of the control; this parameter was found to be positively correlated with the sensitivity of the accommodative system to defocus blur (input of the feedback loop), providing support for the active role of these fluctuations in the accommodative system.
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10.1111/j.1475-1313.1988.tb01032.x
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pubmed_215_21102
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OBJECTIVE
To identify strengths and weaknesses in community based child passenger safety programs by developing a scoring instrument and conducting observations of child restraint use in three Native American communities.
SETTING
The three communities are autonomous Tribal reservations in the Pacific Northwest. Their per capita incomes and rates of unemployment are comparable.
METHODS
In each community, 100 children under 5 years old were observed for car seat use. A six item community assessment tool (100 points maximum) awarded points for such items as the type (primary or secondary) and enforcement of child restraint laws; availability of car seats from distribution programs; extent of educational programs; and access to data on vehicle injuries.
RESULTS
For children from birth to 4 years, the car seat use rate ranged from 12%-21%. Rates for infants (71%-80%) far exceeded rates for 1-4 year old children (5%-14%). Community scores ranged from 0 to 31.5 points. There was no correlation between scores and observed car seat use. One reason was the total lack of enforcement of restraint laws.
CONCLUSIONS
A community assessment tool can highlight weaknesses in child passenger efforts. Linking such a tool with an objective measure of impact can be applied to other injury problems, such as fire safety or domestic violence. The very process of creating and implementing a community assessment can enhance agency collaboration and publicize evidence based "best practices" for injury prevention. Further study is needed to address methodologic issues and to examine crash and medical data in relation to community child passenger safety scores.
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10.1136/ip.8.4.289
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