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pubmed_635_13532 | In view of paediatric drug development, regulatory authorities often request safety studies in juvenile animals, including minipigs. Unfortunately, knowledge on the ontogeny of the biotransformation processes in animal models remains scarce and impedes a correct interpretation of the toxicity findings. CYP3A4 is one of the most important drug-metabolizing enzymes in human beings and shows important similarities with CYP3A in the minipig. Therefore, the aim of this study was to assess the abundance and activity of CYP3A in liver microsomes from foetal, juvenile (days 1, 3, 7 and 28) and adult male and female Göttingen minipigs. CYP3A abundance was studied by an indirect enzyme-linked immunosorbent assay (ELISA), whereas CYP3A activity was assessed by a biotransformation assay with Luciferin-IPA. CYP3A abundance could not be detected until day 3. From day 7 onwards, a gradual increase in expression was noted, leading to the highest abundance in adult animals. CYP3A activity was not detectable in foetuses and 1-day-old animals. The CYP3A activity was detectable, but below the LLOQ in day 3 animals and increased gradually with age to reach the highest level in adults. The CYP3cide and ketoconazole inhibition, and testosterone and midazolam reduction of Luciferin-IPA metabolism in minipig liver microsomes substantiate that Luciferin-IPA is metabolized by CYP3A in minipigs. A positive correlation was found between CYP3A abundance and biotransformation of Luciferin-IPA (Pearson r = 0.863; p < 0.0001). In conclusion, both abundance and activity of CYP3A increased gradually in juvenile minipigs, but remained below the levels observed in adult animals. | 10.1111/bcpt.12410 |
pubmed_632_14073 | In bionanotechnology, the field of creating functional materials consisting of bio-inspired molecules, the function and shape of a nanostructure only appear through the assembly of many small molecules together. The large number of building blocks required to define a nanostructure combined with the many degrees of freedom in packing small molecules has long precluded molecular simulations, but recent advances in computational hardware as well as software have made classical simulations available to this strongly expanding field. Here, we review the state of the art in simulations of self-assembling bio-inspired supramolecular systems. We will first discuss progress in force fields, simulation protocols and enhanced sampling techniques using recent examples. Secondly, we will focus on efforts to enable the comparison of experimentally accessible observables and computational results. Experimental quantities that can be measured by microscopy, spectroscopy and scattering can be linked to simulation output either directly or indirectly, via quantum mechanical or semi-empirical techniques. Overall, we aim to provide an overview of the various computational approaches to understand not only the molecular architecture of nanostructures, but also the mechanism of their formation. | 10.1039/c8cs00040a |
pubmed_694_5107 | Cytologic investigations designed to study bone marrow, peripheral blood, spleen, and thymus of albino rats irradiated by an electromagnetic field, 2375, 2450, and 3000 MEGS, revealed structural and functional changes in populations of megakaryocytes, immunocompetent cells as well as of undifferentiated cells, and of other types of cells that are dependent on the intensity of irradiation and permit establishing the probability-threshold levels of exposure taking account of reactions of perception and physiologic adaptation together with compensatory and regenerative processes and the injury sustained. It is shown that changes in bone marrow cells differentiation and reproduction rather than integral shifts in the peripheral blood that acquire the utmost significance. Subjected to a particular scrutiny in the paper are blast cells, which cells' repopulation was noted to be getting increased in low-intensity exposure as were disturbances in their mitosis pattern. | pubmed_694_5107 |
pubmed_458_1227 | The small copper butterfly, Lycaena phlaeas daimio, has pupal beige/black polymorphism, the development of which is found to be controlled in an apparent association with the development of adult seasonal polymorphism (spring and summer morphs) by photoperiod and temperature in the larval stages. That is, the pupae of beige and black types developed under long-day and short-day conditions tend to develop into brown-winged and red-winged adults, respectively. In addition, a large proportion of long-day pharate pupae chilled at 4 degrees C for 5 days were observed to develop into pupae whose head-thoracic complexes and abdomens were judged to be of the black and intermediate types, respectively. They developed into adults with redder wings as compared to those obtained from unchilled pupae. The results indicate that the physiological mechanism underlying the photoperiodic control of the development of adult seasonal polymorphism may also play a significant role in the determination of pupal beige/black polymorphism in L. phlaeas daimio. Furthermore, cuticle melanization was found to be induced in the head-thoracic complexes of pupae by chilling of the pharate pupae. Melanization of pupal cuticle seems to occur in a close association with the development of reddish-winged adults. | 10.2108/zsj.21.835 |
pubmed_1071_8385 | BACKGROUND
Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. The molecular prognostic model that could be applied to the HCC patient population in general is needed for effectively predicting disease-free survival (DFS).
METHODS
A cohort of 286 HCC patients from South Korea and a second cohort of 83 patients from Hong Kong, China, were used as training and validation sets, respectively. RNA extracted from both tumor and adjacent nontumor liver tissues was subjected to microarray gene expression profiling. DFS was the primary clinical end point. Gradient lasso algorithm was used to build prognostic signatures.
RESULTS
High-quality gene expression profiles were obtained from 240 tumors and 193 adjacent nontumor liver tissues from the training set. Sets of 30 and 23 gene-based DFS signatures were developed from gene expression profiles of tumor and adjacent nontumor liver, respectively. DFS gene signature of tumor was significantly associated with DFS in an independent validation set of 83 tumors (P = 0.002). DFS gene signature of nontumor liver was not significantly associated with DFS in the validation set (P = 0.827). Multivariate analysis in the validation set showed that DFS gene signature of tumor was an independent predictor of shorter DFS (P = 0.018).
CONCLUSIONS
We developed and validated survival gene signatures of tumor to successfully predict the length of DFS in HCC patients after surgical resection. | 10.1245/s10434-013-3070-y |
pubmed_671_11714 | Forty-eight Pasteurella multocida cultures collected from rabbits over a 56-year period were examined to determine their physiological characteristics and to determine their serological types in the gel diffusion precipitin test. Generally, the physiological characteristics from 30 tests were typical for P. multocida. There were a few atypical variations in the fermentation of lactose and maltose and variations in trehalose, dulcitol, xylose, sorbitol, and glycerol. Seven cultures did not produce indole, and four cultures did not produce detectable amounts of hydrogaen sulfide. In obliquely transmitted light, 26 cultures formed large, slightly iridescent, mucoid colonies, 17 cultures had iridescent colonies, and 5 cultures had blue colonies. Heat-stable antigens from the 48 cultures reacted with antisera prepared from P. multocida type cultures presenting serotypes 1, 3, 4, 12, and 15. Antigens from 15 cultures reacted slightly with antisera from more than one serotype. Overall, gel precipitin reactions involving serotype 3 (25%) and serotype 12 (66.7%) were the most prevalent. | 10.1128/jcm.11.6.646-649.1980 |
pubmed_1104_13847 | The relative kinetic stabilities of different 16-mer oligonucleotide duplexes were investigated by source collision-induced dissociation (CID) in a heated capillary electrospray ion source. They were compared with the relative stabilities in solution obtained by thermal denaturation monitored by UV spectrophotometry. The results clearly show that both hydrogen bonding and base stacking interactions that are present in solution are maintained in the gas phase. This suggests that the electrospray process preserves the double-helix structure of DNA. A step by step opening of the double helix structure is proposed for the gas-phase dissociation, competing with the covalent bond cleavage of bases. We also draw attention to the fact that by source CID, it is the kinetic stability of the complexes that is probed. In particular, this implies that only complexes of the same size can be compared. | 10.1002/jms.141 |
pubmed_565_11349 | An infectious cDNA clone of hepatitis E virus was mutated in order to prevent synthesis of either open reading frame 2 (ORF2) protein or ORF3 protein. HuH-7 cells transfected with an ORF2-null mutant produced ORF3, and those transfected with an ORF3-null mutant produced ORF2. Silent mutations introduced into a highly conserved nucleotide sequence in the ORF3 coding region eliminated the synthesis of both ORF2 and ORF3 proteins, suggesting that it comprised a cis-reactive element. A mutant that was not able to produce ORF3 protein did not produce a detectable infection in rhesus macaques. However, a mutant that encoded an ORF3 protein lacking a phosphorylation site reported to be critical for function was able to replicate its genome in cell culture and to induce viremia and seroconversion in rhesus monkeys, suggesting that phosphorylation of ORF3 protein was not necessary for genome replication or for production of infectious virions. | 10.1128/JVI.79.11.6680-6689.2005 |
pubmed_1124_8324 | OBJECTIVE
To compare the clinical and cost-effectiveness of treating recurrent preterm labor with continuous subcutaneous terbutaline versus oral tocolytics in twin gestations.
STUDY DESIGN
In a retrospective, matched-cohort design, twin pregnancies treated as outpatients with continuous subcutaneous terbutaline were identified from a perinatal database, then matched 1:1 by gestational age at recurrent preterm labor to those receiving oral tocolytics. There were 353 patients per treatment group. A cost model was used to compare antepartum hospital, nursery, and outpatient charges.
RESULTS
Infants of the subcutaneous terbutaline group had greater gestational age at delivery, higher birth weights, and less frequent neonatal intensive care unit admission. Charges for antepartum hospitalization and nursery were significantly less in the subcutaneous terbutaline group, while charges for outpatient services were less for the oral group. Mean total estimated charges were US$17,109 less for those receiving subcutaneous terbutaline.
CONCLUSION
Improved clinical outcomes and decreased nursery utilization suggest cost-effectiveness of outpatient continuous subcutaneous terbutaline versus oral tocolytics for the treatment of recurrent preterm labor. | 10.1038/sj.jp.7210553 |
pubmed_159_9920 | OBJECTIVE
This study explores OB/GYN providers' knowledge about published health and healthcare disparities in women's reproductive health.
METHOD
We collected demographic and health disparities knowledge information from OB/GYN providers who were members of ACOG District IV using an online survey (n = 483). We examined differences across groups using statistical tests and regression analyses in a structural equation modeling approach.
RESULTS
Receiving disparities education was positively associated with higher self-reported disparities knowledge and disparities quiz performance (p < 0.05). African American/Black providers had higher quiz scores than their white counterparts, and providers varied in their levels of disparities knowledge across practice settings (p < 0.05).
CONCLUSIONS
Differences in levels of knowledge of racial/ethnic disparities in health and healthcare outcomes among OB/GYN providers varied across race/ethnicity, practice context, and whether providers had received formal disparities education. Future research should explore these differences at a population level and develop interventions to improve health disparities education among OB/GYN providers. | 10.1016/j.jnma.2020.03.009 |
pubmed_598_9970 | Proteins that are to be eliminated must be proficiently recognized by proteolytic systems so that inadvertent elimination of useful proteins is avoided. One mechanism to ensure proper recognition is the presence of N-terminal degradation signals (N-degrons) that are targeted by adaptor proteins (N-recognins). The members of the caseinolytic protease S (ClpS) family of N-recognins identify targets bearing an N-terminal phenylalanine, tyrosine, tryptophan or leucine residue, and then present them to a protease system. This process is known as the 'bacterial N-end rule'. The presence of a ClpS protein in Arabidopsis thaliana chloroplasts (AtClpS1) prompted the hypothesis that the bacterial N-end rule exists in this organelle. However, the specificity of AtClpS1 is unknown. Here we show that AtClpS1 has the ability to recognize bacterial N-degrons, albeit with low affinity. Recognition was assessed by the effect of purified AtClpS1 on the degradation of fluorescent variants bearing bacterial N-degrons. In many bacterial ClpS proteins, a methionine residue acts as a 'gatekeeper' residue, fine-tuning the specificity of the N-recognin. In plants, the amino acid at that position is an arginine. Replacement of this arginine for methionine in recombinant AtClpS1 allows for high-affinity binding to classical N-degrons of the bacterial N-end rule, suggesting that the arginine residue in the substrate-binding site may also act as a gatekeeper for plant substrates. | 10.1093/pcp/pcy016 |
pubmed_279_11509 | The development of carcinoma in the neovagina has rarely been reported. Depending on the type of tissue that has been used for the transplant, the tumor appears either as a squamous cell carcinoma or adenocarcinoma. It is important to draw a distinction not only between the patients with squamous cell carcinoma and adenocarcinoma, but also between those with neovagina performed due to congenital absence of the vagina and others in whom the procedure was performed because of an advanced cancer in the true pelvis. In the latter group of patients, it is generally difficult to distinguish a residual disease from a second primary of the same histology. There is no dilemma, however, when the histology differs as in the case presented. The patient reported here underwent surgery for squamous cell carcinoma of the cervix, stage Ib, in 1967. The intervention comprised a Wertheim-Meigs resection and sigmoid vaginoplasty. Considering the favourable histological findings, postoperative irradiation was not indicated. Following the procedure, the patient had been well and free of any major complaint for 22 years after surgery when she presented with a moderately differentiated adenocarcinoma of the neovagina. She was successfully operated upon and had no evidence of disease at the last follow-up examination, two and a half year after surgery. | pubmed_279_11509 |
pubmed_360_10877 | The authors report histological and clinical analysis of 7 patients with malignant proliferation of the stromal colls in the endometrium. In 3 patients the histological pattern differed form that in the remaining cases in a greater number of cell divisions and higher grade of cell atypia. Despite this, the clinical pattern was similar in nearly all cases. The reported material cannot support the hypothesis of two forms of the disease: stromal sarcoma and stromatosis. Both these diagnoses carry a poor prognosis. | pubmed_360_10877 |
pubmed_492_17834 | Previous research suggests differences between women and men in the clinical features of schizophrenia, but studies examining sex differences in neuropsychological functioning have reached inconsistent results. In the present study, sex differences in cognition and clinical features were investigated in population-based samples of participants with schizophrenia (n=218), their healthy first-degree relatives (n=438) and controls (n=123). Sex differences in illness features were small; nevertheless, women with schizophrenia had less negative symptoms and lived independently more often than men. The schizophrenia group had impairments in all studied neuropsychological domains, and the relatives were impaired in processing speed and set-shifting. In all groups, women performed better than men in processing speed, set-shifting and verbal episodic memory, whereas men outperformed women in visual working memory. The group-by-sex interaction was significant in two variables: women outperformed men in the relatives group in immediate verbal reproduction and in the use of semantic clustering as a learning strategy, while there was no sex difference in the schizophrenia group. In conclusion, sex differences in cognition are mostly similar in schizophrenia to those among controls, despite sex differences in illness features. The preservation of sex differences also in first-degree relatives supports the conclusion. | 10.1016/j.psychres.2010.11.009 |
pubmed_594_21202 | The smallest known collagens with only 14 Gly-X-Y repeats referred to as minicollagens are the main constituents of the capsule wall of nematocysts. These are explosive organelles found in Hydra, jellyfish, corals and other Cnidaria. Minicollagen-1 of Hydra recombinantly expressed in mammalian 293 cells contains disulfide bonds within its N- and C-terminal Cys-rich domains but no interchain cross-links. It is soluble and self-associates through non-covalent interactions to form 25-nm-long trimeric helical rod-like molecules. We have used a polyclonal antibody prepared against the recombinant protein to follow the maturation of minicollagens from soluble precursors present in the endoplasmic reticulum and post-Golgi vacuoles to the disulfide-linked insoluble assembly form of the wall. The switch from intra- to intermolecular disulfide bonds is associated with 'hardening' of the capsule wall and provides an explanation for its high tensile strength and elasticity. The process is comparable to disulfide reshuffling between the NC1 domains of collagen IV in mammalian basement membranes. | 10.1093/emboj/20.12.3063 |
pubmed_86_12823 | Gangliosides were evaluated for their ability to inhibit the phenotype and function of an encephalitogenic T-helper lymphocyte line from Lewis rats (BP-1), which responds specifically to guinea pig myelin basic protein (GP-BP). After activation for 3 days with GP-BP, the BP-1 line induced a lethal form of experimental autoimmune encephalomyelitis (EAE) in recipient rats 3-6 days after intraperitoneal injection. Incubation of activated BP-1 line cells with 250 microM gangliosides for 1 hr prior to injection prevented EAE completely in 5/14 recipients and markedly reduced the severity of clinical signs and histologic lesions in the rest. Similar treatment of BP-1 cells with galactocerebroside had no inhibitory effect. Both individual and mixed gangliosides inhibited accessory cell-dependent activation of BP-1 cells with GP-BP. Gangliosides also inhibited BP-1 activation with a cell-free supernatant containing accessory cell-processed GP-BP and rat Ia molecules, suggesting that the inhibition was not restricted to accessory cell function. In addition to inhibiting antigen-dependent proliferation, gangliosides inhibited IL-2 dependent cell growth. Furthermore, individual and mixed gangliosides blocked binding of anti-T-helper cell antibody (W3/25) to the BP-1 line, while galactocerebroside, ceramide, and sialic acid had no inhibitory effect. Cell surface staining of T-total, T-non-helper, or Ia determinants was relatively unaffected by gangliosides. Taken together, the immunomodulatory properties of gangliosides on T-effector cell function lend biologic importance to the increased levels of gangliosides which have been reported in human diseases with immunoregulatory abnormalities such as multiple sclerosis, rheumatoid arthritis, and cancer. | 10.1016/0008-8749(85)90297-7 |
pubmed_999_9952 | Ligand design is at the forefront of many advances in various areas of chemistry such as organometallic chemistry, functional materials, and homogeneous catalysis [...]. | 10.3390/molecules26082132 |
pubmed_779_16456 | Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is preferred for evaluating malignant lymph nodes and staging of lung cancer. Nevertheless, larger tissue samples are increasingly needed, particularly for molecular analysis. We describe the feasibility, technical details, and complications of EBUS-guided transbronchial cryo-node biopsy (TBCNB) in four patients with mediastinal adenopathy. The samples obtained by EBUS-TBCNB in all cases were adequate for histopathological examination (HPE) and immunohistochemistry (IHC) staining. In case 1, HPE showed non-caseating epithelioid granuloma with giant cells and fibrosis consistent with sarcoidosis. Case 2 was diagnosed with adenocarcinoma with positivity for ROS1(D4D6). Case 3 showed features of metastatic adenocarcinoma from the breast (positive for Her2, ER, and GATA3). Case 4 was diagnosed with tuberculosis (necrotizing granuloma in histopathology, stain with Ziehl-Neelsen that showed few rod-shaped bacilli). Only one patient had minimal bleeding at the puncture site controlled with cold saline. There were no adverse events such as major bleeding, pneumomediastinum, or pneumothorax. | 10.1002/rcr2.808 |
pubmed_732_14777 | Mimadiestra gen. nov. (type species: M. biloba sp. nov.) is described from Thailand. Megadiestramima Storozhenko et Gorochov, 1992 and Leodiestramima Storozhenko, 2009, stat. nov. are considered as separate genera, therefore, three new combinations are proposed: Leodiestramima exculta (Gorochov, 1998), comb. nov., L. lecta (Gorochov, 1998), comb. nov., L. orlovi (Gorochov, 1994), comb. nov. A key to genera of the tribe Diestramimini is given. | 10.11646/zootaxa.3765.3.5 |
pubmed_529_10601 | BACKGROUND
The lack of proven efficacy of new healthcare interventions represents a problem for health systems globally. It is partly related to suboptimal implementation processes, leading to poor adoption of new interventions. Activation of Stratification Strategies and Results of the interventions on frail patients of Healthcare Services (ASSEHS) EU project (N° 2013 12 04) aims to study current existing health Risk Stratification (RS) strategies and tools on frail elderly patients. This paper aims at identifying variables that make the implementation of population RS tools feasible in different healthcare services.
METHODS
Two different methods have been used to identify the key elements in stratification implementation; i) a Scoping Review, in order to search and gather scientific evidence and ii) Semi-structured interviews with six key experts that had been actively involved in the design and/or implementation of RS strategies. It aims to focus the implementation construct on real-life contextual understandings, multi-level perspectives, and cultural influences.
RESULTS
A Feasibility Framework has been drawn. Two dimensions impact the feasibility of RS: (i) Planning, deployment and change management and (ii) Care intervention. The former comprises communication, training and mutual learning, multidisciplinarity of the team, clinicians' engagement, operational plan and ICT display and functionalities. The latter includes case finding and selection of the target population, pathway definition and quality improvement process.
CONCLUSIONS
The Feasibility Framework provides a list of key elements that should be considered for an effective implementation of population risk stratification interventions. It helps to identify, plan and consider relevant elements to ensure a proper RS implementation. | 10.1186/s12913-017-2275-3 |
pubmed_115_18840 | Helicity of membrane proteins can be manifested inside the ribosome tunnel, but the determinants of compact structure formation inside the tunnel are largely unexplored. Using an extended nascent peptide as a molecular tape measure of the ribosomal tunnel, we have previously demonstrated helix formation inside the tunnel. Here, we introduce a series of consecutive polyalanines into different regions of the tape measure to monitor the formation of compact structure in the nascent peptide. We find that the formation of compact structure of the polyalanine sequence depends on its location. Calculation of free energies for the equilibria between folded and unfolded nascent peptides in different regions of the tunnel shows that there are zones of secondary structure formation inside the ribosomal exit tunnel. These zones may have an active role in nascent-chain compaction. | 10.1038/nsmb1021 |
pubmed_118_5940 | Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products. Here, we used a chromatographic process using a new resin that binds with high capacity to IgG and removes procoagulant activities. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: <1.56 mIU/mL, chromogenic FXIa assay: <0.16 mIU/mL, non-activated partial thromboplastin time (NaPTT): >250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a concentration 32.5 times higher than the concentration in normal specimens, the procoagulant activities were below the detection limit (<0.31 ng/mL). These results demonstrate the ability of our manufacturing process to remove procoagulant activities to below the detection limit (except by NaPTT), suggesting a reduced risk of thromboembolic events that maybe potentially caused by our IVIG preparation. | 10.1016/j.biologicals.2016.11.002 |
pubmed_308_2665 | INTRODUCTION
The association between obesity and asthma control/quality of life commonly relies on body mass index (BMI) as the anthropomorphic measure. Due to limitations of BMI and the existence of alternative measures, such as neck circumference (NC), we examined the association between NC and asthma control/quality of life, with particular attention to male-female differences.
MATERIALS AND METHODS
The AsthMaP-2 Project is an observational study of youth with physician-diagnosed asthma. NC was stratified according to age- and sex-specific cutoffs and associated with asthma control (via Asthma Control Test [ACT]) and quality of life (via Integrated Therapeutics Group [ITG]-Asthma Short Form).
RESULTS
The mean ± SD age was 11.9 ± 3.6 years, and 53% were male (N = 116). The mean BMI percentile was at the 71 ± 28 percentile. Thirty-one participants (27%) met criteria for high NC. Males with high NC had significantly worse asthma control (P = 0.02) and lower quality of life than those with low NC. No similar association was found for females and the proportion of variability in ACT and ITG was best explained by BMI percentile. Conversely, for males, the proportion of variability in these scores explained by NC was larger than BMI percentile alone (Cohen's f(2) = 0.04-0.09, a small to medium effect size).
DISCUSSION
Among male youth with asthma, combined use of NC and BMI percentile explained asthma control and quality of life better than BMI alone. Future studies of asthma should include measurement of NC and other anthropogenic measures of regional adiposity to clarify sex differences in asthma. Pediatr Pulmonol. 2016; 51:893-900. © 2016 Wiley Periodicals, Inc. | 10.1002/ppul.23381 |
pubmed_953_19343 | Elevated free radical generation in inflamed joints and impaired antioxidant system has been implicated in rheumatoid arthritis (RA). Green tea extracts (GTE) have been shown to reduce inflammation in inflammatory arthritis murine model. This study investigates possible mechanisms by which vitamin C and GTE protect joints in RA rat model. This study included forty adult male rats that were divided into four groups (10 rats each); control group, collagen II induced RA group (CII), CII treated with vitamin C (CII + Vit C) and CII treated with GTE (CII + GTE) in physiology laboratory, Assiut University, Egypt. After 45 days of treatment, plasma levels of lipid peroxides (LPO), nitric oxide (NO), ceruloplasmin (CP), superoxide dismutase (SOD), uric acid (UA) and glutathione (GSH) were detected using colorimetric methods, PGE(2) using ELISA and copper (Cu) and zinc (Zn) using spectrometer. In CII group, levels of LPO, NO, PGE(2), UA, CP, Cu were higher while SOD, GSH, Zn were lower than controls. In groups treated with vitamin C and GTE, levels of SOD, GSH were increased while levels of LPO, NO, PGE(2), Cu, CP were decreased compared with CII group. Levels of UA were decreased and Zn increased in GTE treated group compared with CII group. GTE treated group showed higher Zn and low Cu levels compared with vitamin C treated group. This study suggests proper GTE and vitamin C intake may effectively normalize the impaired oxidant/antioxidant system and delaying complication of RA. | 10.1007/s12291-009-0053-7 |
pubmed_27_14905 | 2,4-Dichloro-6-aminophenol (DCAP) is a major metabolite of the herbicide 2,4-dichloro-6-nitrophenol ammonium (DCNPA). In our previous studies this metabolite, but not the parent compound, was found to induce sister chromatid exchanges (SCEs) and micronucleus (MN) formation in Chinese hamster lung fibroblasts (V79 cells). Further studies were carried out to determine whether DCAP can also induce structural chromosomal aberrations (CAs) in cultured V79 cells. The assay was performed under three different treatment conditions: 1) 3 h treatment followed by 17 h post-treatment incubation. 2) 12 h treatment, and 3) 20 h treatment with multiple sampling times. Results showed that CAs were induced by DCAP in V79 cells. The aberrations were mainly chromatid types (gaps, breaks, and deletions), triradials, quadriradials, and complex rearrangements. However, induction of CAs appears to be dependent on the treatment condition. The 3 h treatment following a 17 h post-treatment incubation gave rise to 24% aberrant cells (excluding gaps) and a total of 44 aberrations per 100 metaphases, while the 12 h treatment only gave a borderline response and the 20 h treatment did not yield a significant increase of CAs at any concentration tested. It seems that a short-term treatment with higher concentrations is a better treatment protocol for genotoxicity studies of certain cytotoxic chemicals such as DCAP. Results of this study further indicate that the herbicide DCNPA is potentially hazardous to the exposed population. | 10.1002/(SICI)1520-6866(1996)16:2<81::AID-TCM2>3.0.CO;2-B |
pubmed_798_19972 | Recently a large amount of new data on the plasticity of stem cells of various lineages have emerged, providing new perspectives especially for the therapeutic application of adult stem cells. Previously unknown possibilities of cell differentiation beyond the known commitment of a given stem cell have been described using keywords such as "blood to liver," or "bone to brain." Controversies on the likelihood, as well as the biological significance, of these conversions almost immediately arose within this young field of stem cell biology. This chapter will concentrate on these controversies and focus on selected examples demonstrating the technical aspects of stem cell transdifferentiation and the evaluation of the tools used to analyze these events. | 10.1007/10_2008_49 |
pubmed_631_2253 | OBJECTIVES
To examine contemporary survival patterns in the general population of patients diagnosed with chronic myeloid leukaemia (CML), and to identify patient groups with less than optimal outcomes.
DESIGN
Prospective population-based cohort.
SETTING
The UK's Haematological Malignancy Research Network (catchment population 3.6 million, with >2000 new haematological malignancies diagnosed annually).
PARTICIPANTS
All patients newly diagnosed with CML, from September 2004 to August 2011 and followed up to 31 March 2013.
MAIN OUTCOME MEASURE
Incidence and survival.
RESULTS
With a median diagnostic age of 59 years, the CML age standardised (European) incidence was 0.9/100 000 (95% CIs 0.8 to 0.9), 5-year overall survival was 78.9% (72.3 to 84.0) and 5-year relative survival 88.6% (81.0 to 93.3). The efficacy of treatment across all ages was clearly demonstrated; the relative survival curves for those under 60 and over 60 years being closely aligned. Survival findings were similar for men and women, but varied with deprivation; the age and sex adjusted HR being 3.43 (1.89 to 6.22) for deprivation categories 4-5 (less affluent) versus 1-3 (more affluent). None of these differences were attributable to the biological features of the disease.
CONCLUSIONS
When therapy is freely provided, population-based survival for CML is similar to that reported in clinical trials, and age loses its prognostic significance. However, although most of the patients with CML now experience close to normal lifespans, those living in more deprived areas tend to have poorer outcomes, despite receiving the same clinical care. A significant improvement in overall population outcomes could be achieved if these socioeconomic differences, which may reflect the treatment compliance, could be eliminated. | 10.1136/bmjopen-2013-004266 |
pubmed_1138_3441 | The administration of erythropoietin (EPO) in maintenance hemodialysis may affect urea kinetic parameters by altering dialyzer function during first use and reuse, and dietary protein intake as a consequence of increased appetite. In the present study, the effect of EPO treatment on urea kinetic parameters in case of reuse (n = 14) and first use (n = 10) of dialyzers was assessed in 24 clinically stable hemodialysis patients who were evaluated before and during EPO treatment. In addition, the heparin need and the number of uses before discarding the dialyzer were registered. No significant differences between urea kinetic parameters before compared with during EPO treatment were noted in the overall population or in the subgroups treated with reused or first-use dialyzers. However, in 13 patients with a low baseline protein catabolic rate (pcr(wt)) (pcr(wt) < 1.0 g/kg/24 hr before EPO treatment), pcr(wt) increased from 0.81 +/- 0.04 to 0.93 +/- 0.06 (+ 15%, P < 0.01). The heparin dosage increased from 6,693 +/- 419 IU/session to 7,659 +/- 566 IU/session and from 5,538 +/- 594 IU/session to 6,918 +/- 649 IU/session (P < 0.05) in the subgroups treated with reused or first-use dialyzers, respectively. Nevertheless, when dialyzer reprocessing was performed, the number of achieved uses before discarding the dialyzers was reduced after the introduction of EPO (5.4 +/- 0.4 v 3.4 +/- 0.4, P < 0.01). In conclusion, during EPO treatment urea kinetic parameters were not affected in case of dialyzer first use or in case of reuse. In patients with low pretreatment values, pcr(wt) increased, possibly indicating improved protein intake in malnourished patients.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1016/s0272-6386(12)80812-2 |
pubmed_960_972 | Malaria is a serious health problem in developing countries. With the complete sequencing of the genomes of the parasite and of the mosquito vector, malaria research has entered the post-genome era. In this report we summarize the results and new research avenues presented at a recent meeting held with the aim of developing interdisciplinary approaches to combat this disease. | 10.1111/j.1365-2958.2004.04362.x |
pubmed_94_10660 | Traditionally, clinicians have assumed the primary responsibility for evaluating disease- and treatment-related outcomes. In the past few decades, however, a series of recommendations and standards promulgated by professional societies and regulatory agencies have resulted in increased use of patient-reported outcome (PRO) measures in cancer clinical trials. PROs, such as quality of life (QOL) measures, are important in establishing overall treatment effectiveness in cancer clinical trials, and they can inform clinical decision making. This article discusses the current state of the science in PRO research for patients with lung cancer, the cancer type with the highest incidence rate and the lowest survival rate worldwide. The discussion focuses on (1) PRO and survival; (2) electronic PRO reporting and interventions; (3) PROs and immunotherapy; (4) PRO, biomarkers, and precision health; (5) key issues in applying PROs in clinical trials; and (6) future directions for research. | 10.1055/s-0040-1712099 |
pubmed_943_4983 | The switch to the angiogenic phenotype represents a critical checkpoint during tumor progression. The acquisition of new capillary vessels provides newly vascularized tumor nodules with a distinct biological advantage over their avascular counterparts by conferring upon them the ability to expand and develop both locally and metastatically. To identify the molecules and mechanisms underlying this rate-limiting step in successful tumorigenesis, we have developed an in vivo tumor model that reproducibly recapitulates the angiogenic switch. Using this model, we have analyzed vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hypoxia-inducible factor-1alpha (HIF-1alpha) expression and activity in both avascular and vascular growth phases of the tumor. A significantly higher level of VEGF protein was detected in avascular tumor nodules compared with vascular nodules. As avascular tumors became vascularized, VEGF levels decreased approximately 10-fold. In contrast, bFGF levels were not elevated in avascular nodules but rather were detected at levels approximately 2 times higher in vascular nodules compared with the avascular tumor nodules. Given that VEGF is transcriptionally regulated by HIF-1alpha, immunohistochemical studies of chondrosarcoma nodules were conducted and revealed that the nuclear translocation of HIF-1alpha was detected exclusively in avascular tumor nodules. This study implicates HIF-1alpha-mediated up-regulation of VEGF but not bFGF in the switch to the angiogenic phenotype during tumorigenesis. | pubmed_943_4983 |
pubmed_392_785 | BACKGROUND
Patients experience limitation of hip joint movement due to coxarthrosis, such limitation may affect the quality of sexual activity in patients. We aimed at investigating the postoperative quality of sexual life and evaluating the clinical satisfaction of patients who underwent bilateral total hip arthroplasty.
HYPOTHESIS
Postoperative sexual life quality improvement in patients undergoing bilateral total hip arthroplasty increases clinical satisfaction.
METHODS
The study included patients who underwent staged bilateral total hip arthroplasty surgery between June 2016 and January 2019. Each patient was evaluated using the sexual quality of life-female (SQOL-F) or Sexual quality of life-male (SQOL-M) questionnaire containing similar questions for both genders regarding sexual satisfaction.
RESULTS
Among all the individuals, 32 were sexually active (13 females, 19 males), and seven were not sexually active (6 females, 1 male) before the surgery. Among the 29 individuals (18 females, 11 males) who thought that their sexual life was negatively affected even before the surgery, 10 (1 female, 9 males) were found not to be negatively affected. Moreover, the sexual life of 18 females was negatively affected 27.93±14.5 months (range, 12-43) before hip arthroplasty and 11 males was negatively affected 19.5±11.0 months (range, 8-31) before the surgery as well. Twenty (10 females, 10 males) individuals stated an improvement in their sexual life, 13 (6 females, 7 males) individuals stated no change. Unfortunately, 6 (3 females, 3 males) individuals stated a degradation of their sexual activity after hip arthroplasty. Patients gained more than 60 degrees of hip range of motion and experienced significant reduction in pain after hip joint movements after surgery.
DISCUSSIONS
In our study, we evaluated sexual limitations before and after total hip arthroplasty surgery and postoperative sexual quality of life. Due to the increased range of motion of patients after surgery, the proportion of sexually active individuals increased and the sexual quality of life reached a satisfactory level.
LEVEL OF EVIDENCE
III; retrospective cohort study. | 10.1016/j.otsr.2021.103125 |
pubmed_582_19971 | We have analysed the management and clinical outcome of a series of consecutive patients who had a total hip replacement and developed post-operative surgical site infection (SSI) with methicillin-resistant Staphylococcus aureus. The incidence of this infection was 1% over a period of five years. We studied SSI in 15 patients (16 infections) with a mean age of 72.7 years (53 to 81). In all, 12 of the infections occurred early and half of the infections involved the prosthesis, resulting in an increase of 11-fold in the cumulative hospital stay. Methicillin-resistant Staph. aureus was successfully eradicated in all the patients after a mean follow-up of 53.6 months (25 to 88). Superficial incisional infections resolved after antibiotic therapy alone while deep infections required multiple operative debridements. Attempted retention of the implant in early organ space infections was successful in only one of five patients. Only three patients with implant-level infections obtained a pain-free, functional prosthesis while a further three required excision arthroplasty. We have formulated a protocol of treatment which may serve as a guide in the management of these infections. | 10.1302/0301-620X.90B3.20155 |
pubmed_879_7711 | Low back pain (LBP) is a prevalent musculoskeletal disease that affects a large percentage of the working population, including teachers. The World Health Organization has identified the school as an effective environment for improving child health. For this reason, the figure of the teacher is a fundamental piece in the process of knowledge acquisition about postural education and prevention of LBP among schoolchildren. The present study aims to determine the knowledge of postural education and back pain prevention among primary school teachers. This cross-sectional study evaluated 85 primary school teachers from Majorca (Spain), of whom 17.6% were physical education teachers and 82.4% were classroom teachers. The study was based on two different structured and self-administered questionnaires to investigate into specific knowledge about LBP: Low Back Pain Knowledge Questionnaire (LKQ) and COSACUES-AEF Questionnaire. The results demonstrated a lifetime prevalence of LBP of 96.5% with significant differences determined by sex. The knowledge of participants about LBP was 17.3 in LKQ (range scale 0-24) and 4.3 in COSACUES (range scale 1-10). In conclusion, the teachers knowledge is insufficient to carry out an efficient and useful health promotion program among schoolchildren to prevent LBP. | 10.3390/ijerph182111306 |
pubmed_869_9490 | Volatiles carried by magmas, either dissolved or exsolved, have a fundamental effect on a variety of geological phenomena, such as magma dynamics and the composition of the Earth's atmosphere. In particular, the redox state of volcanic gases emanating at the Earth's surface is widely believed to mirror that of the magma source, and is thought to have exerted a first-order control on the secular evolution of atmospheric oxygen. Oxygen fugacity (f(O2) estimated from lava or related gas chemistry, however, may vary by as much as one log unit, and the reason for such differences remains obscure. Here we use a coupled chemical-physical model of conduit flow to show that the redox state evolution of an ascending magma, and thus of its coexisting gas phase, is strongly dependent on both the composition and the amount of gas in the reservoir. Magmas with no sulphur show a systematic f(O2) increase during ascent, by as much as 2 log units. Magmas with sulphur show also a change of redox state during ascent, but the direction of change depends on the initial f(O2) in the reservoir. Our calculations closely reproduce the H2S/SO2 ratios of volcanic gases observed at convergent settings, yet the difference between f(O2) in the reservoir and that at the exit of the volcanic conduit may be as much as 1.5 log units. Thus, the redox state of erupted magmas is not necessarily a good proxy of the redox state of the gases they emit. Our findings may require re-evaluation of models aimed at quantifying the role of magmatic volatiles in geological processes. | 10.1038/nature05509 |
pubmed_597_24599 | Aneurysm of the mitral valve (AMV) is rarely reported. The etiology of this unusual pathology is commonly attributed to aortic valve endocarditis (AVE) with aortic regurgitation (AR) or connective tissue disease. We present two recent cases of AMV with good correlation between pre-operative trans-esophageal echocardiography (TEE), intra-operative real-time 3-dimensional echocardiography (RT-3D-Echo) and surgical findings. The importance of diligent surveillance by TEE in patients with AVE for occurrence of AMV is emphasized. The literature on this topic is briefly reviewed. | 10.1016/j.jsha.2012.11.002 |
pubmed_234_14303 | Adoption and medically assisted reproduction are alternative options for childless parents to fulfill their wish for having a child. In both situations, there is a necessity for the future parents to mourn the loss of their imagined child, which could have been conceived without a third party (adoption agency or medically assisted reproduction). Adoption always represents for the child a loss of emotional ties with birthparents and the development of new attachments with adoptive parents. Adoption can be considered as a lifetime process of the members involved in the adoption triangle, that is birth parents, adoptive parents and the child. The article discusses the loss of emotional bonds from primary caretakers as a psychological trauma and addresses mourning difficulties in adoptees. Problems with the development of new attachments with adoptive parents such as loyalty conflicts and the revelation of the adoption are described. Family romance fantasy in adoption and aspects of family dynamics as well as the specific difficulties adoptive parents encounter are explored. | 10.1024/0040-5930.56.5.251 |
pubmed_452_16712 | Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/ Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p < 0.001), low skeletal muscle density (p < 0.05), and timed up and go test failure (p < 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p < 0.05) and hand grip strength test failure (p < 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p < 0.05), low visceral obesity (p < 0.01), and low skeletal muscle density (p < 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer. | 10.3390/cancers12051187 |
pubmed_275_3954 | The responsiveness of the cerebral circulation to acute increases in mean arterial pressure was studied before and during the administration of propofol 3, 6, or 12 mg/kg/h in the anaesthetised baboon. Although mean arterial pressure increased significantly on each occasion, there were no significant changes in cerebral blood flow. This indicates that the physiological responsiveness of the cerebral circulation to alterations in mean arterial pressure was preserved during the administration of propofol in the concentrations studied. | 10.1097/00008506-198912000-00015 |
pubmed_605_10608 | Sensory memory is capable of recording information and giving feedback based on external stimuli. Haptic memory in particular can retain the sensation of the interaction between the human body and the environment and help humans to describe the physical quantities in their environment and manipulate objects in daily activities. Although sensitive and accurate tactile sensors have been produced on optical and electronic devices, their rigorous operation and equipment requirements seriously limit their further applicability. In addition, their poor retainability after the removal of external stimuli also warrants further improvements. Thus, haptic memory materials, having simple structures and high sensitivity, are highly desired. Herein, we successfully developed two piezochromic assemblies assisted by halogen bonding for haptic memory. The halogen bond not only contributes to the fabrication of the network and enhances integrative stability but also broadens the natural piezofluorescent range, thus promoting sensory sensitivity. Moreover, the colorimetric change of the assemblies could be well-retained after the stimulus was removed. Upon mild heating treatment, the piezochromic response could be recovered to its original state, confirming the recyclability of this haptic memory material for use in practical applications. The present work enriches the library of piezochromic materials with enhanced performance for haptic memory. | 10.1021/jacs.6b11057 |
pubmed_918_23562 | We identified a strain of Alphacoronavirus 1, FCoV-SB22, from a pool of fecal samples from domestic cats from a rural settlement in the municipality of Santa Bárbara, Pará, Brazil. The nucleotide identity with feline coronavirus was 91.5%. The present study reports the first complete genome sequence of a feline coronavirus from Brazil. | 10.1128/MRA.01535-18 |
pubmed_975_10405 | The purpose of this investigation was to establish whether the tissue response and migration of polyethylene debris differed at noncemented smooth and porous implant surfaces. This was accomplished through 3 separate but closely related studies: (1) a canine cylindrical implant model with smooth and porous surfaces exposed to polyethylene debris; (2) a canine total hip arthroplasty model analyzing the interface between bone and femoral implants with various porous-coating configurations; and (3) a histologic analysis of autopsy-retrieved, human, noncemented hip prostheses with noncircumferential porous coating. The cylindrical implant model involved the placement of split cylinders, 1/2 porous and 1/2 smooth, into the distal femur and proximal tibia of 4 dogs. Four control implants and 10 test implants (chronically exposed to simulated polyethylene debris with a mean size of 4.7 microns) were examined histologically as long as 30 weeks after surgery. The canine hip study involved the study of 54 noncemented hip prostheses at periods of 1, 6, and 24 months. The prostheses possessed 4 different porous surface configurations: 1 with circumferential porous coating, 2 with noncircumferential coating, and 1 without porous coating. The human retrieval analysis involved the study of 7 cadaveric femora (age, 6 months-5 years) implanted with a straight titanium-alloy prosthesis possessing proximal pads of titanium fiber metal on the anterior, posterior, and medial aspects. With all implants in all 3 studies, there was the common finding of bone ingrowth at the porous implant surface and a fibrous interface or periprosthetic cavity around the portion of the implant that was smooth surfaced. The periprosthetic cavity typically was encapsulated by a thin continuous shell of trabecular bone. In addition, polyethylene debris was found to have preferentially migrated along the smooth implant surfaces. In the longer-term canine and human hip retrievals, polyethylene particles in the micron size range were present within histiocytes, whereas larger particles as much as 100 microns were found within foreign-body giant cells. Of importance for the implants from all 3 studies, with the exception of some pronounced cavities on the lateral aspect of the human hip prostheses, the periimplant cavities around the smooth surfaces were not detectable radiographically. This study clearly established a fundamental principle of relative barriers to particulate debris migration. Smooth implant surfaces are more susceptible than porous surfaces to the development of a fibrous tissue filled periimplant cavity and the subsequent migration of polyethylene wear debris.(ABSTRACT TRUNCATED AT 400 WORDS) | pubmed_975_10405 |
pubmed_1065_8017 | The primary goal of this research was to investigate the possibility that being very invested in goals has psychological trade-offs. Self-report methods were used in a concurrent study with college students (Study 1) and a longitudinal study with elementary school children (Study 2). The results of both studies provided support for the hypothesis that high goal investment has psychological trade-offs. Such investment was associated with positive emotions as well as with worrying, both concurrently and longitudinally. In addition, evidence for mediational mechanisms was provided: Perceptions of accomplishment accounted for the relation between goal investment and positive emotions; the link between goal investment and worrying was mediated by predictions that failure would be upsetting. The implications of these findings for distinguishing between depressive and anxiety symptoms are discussed. | pubmed_1065_8017 |
pubmed_1004_843 | We investigate electro- and thermo-optic effects on multi-wavelength Solc filters based on chi(2) nonlinear quasi-periodic photonic crystals. The multi-wavelength Solc filters are composed of two building blocks A and B, in which each containing a pair of antiparallel poled domains, arranged as a Fibonacci sequence. The transmittances at filtering wavelengths can be modulated from 0 to 100% by applying an external voltage but the filtering wave-lengths are unchanged. The filtering wavelengths can be tuned by varying temperature. As temperature decreases, the filtering wavelengths increase (approximately -0.45 nm/degrees C). | 10.1364/oe.16.006098 |
pubmed_223_14963 | Objective: Parental views about the outcomes of implantation on the child's quality of life are valuable sources of information for implantation specialists. The aim at this study was to validate the "Parental Perspectives" questionnaire in Persian language.Design: The original questionnaire was translated from English to Persian language; the final Persian version of questionnaire was prepared and evaluated for validity and reliability. The internal consistency of the questionnaire and test-retest reliability were respectively evaluated by Cronbach's alpha and ICC index. Factor analysis was used to determine the construct validity.Study Sample: The participants of this study were 370 parents of CI children.Results: Sampling adequacy for executing of factor analysis was confirmed by the results of Kaiser-Meyer-Olkin (=0.84) and Bartlett test (p < .05). Three factors were extracted from exploratory factor analysis. Confirmatory factor analysis confirmed the accuracy of the three-dimensional structures. Principal component analysis revealed the structural validity of three factors. Correlation between questionnaire items was good (r = 0.76). Reliability coefficient was calculated as 0.93.Conclusions: The Persian version of the questionnaire has good validity and reliability and can be used to examine the perspectives of the parents about CI. | 10.1080/14992027.2020.1721576 |
pubmed_81_4091 | Myocardial regeneration with stem-cell transplantation is a possible treatment option to reverse deleterious effects that occur after myocardial infarction. Since little is known about stem cell survival after transplantation, developing techniques for "tracking" cells would be desirable. Iron-oxide-labeled stem cells have been used for in vivo tracking using MRI but produce negative contrast images that are difficult to interpret. The aim of the current study was to test a positive contrast MR technique using reduced z-gradient rephasing (GRASP) to aid in dynamically tracking stem cells in an in vivo model of mouse myocardial infraction. Ferumoxides and protamine sulfate were complexed and used to magnetically label embryonic stem cell-derived cardiac-precursor-cells (ES-CPCs). A total of 500,000 ES-CPCs were injected in the border zone of infarcted mice and MR imaging was performed on a 9.4T scanner using T(2)*-GRE sequences (negative contrast) and positive contrast GRASP technique before, 24 hours, and 1 week after ES-CPC implantation. Following imaging, mice were sacrificed for histology and Perl's staining was used to confirm iron within myocardium. Good correlation was observed between signal loss seen on conventional T(2)* images, bright areas on GRASP, and the presence of iron on histology. This demonstrated the feasibility of in vivo stem cell imaging with positive contrast MRI. | 10.1002/mrm.21642 |
pubmed_891_1766 | Calcium (Ca2+) is an essential nutrient element for plants as it stabilizes the membrane system structure and controls enzyme activity. To investigate the effects of Ca2+ on plant growth and leaf photosynthetic electron transport in oat (Avena sativa) under NaCl stress, oat seeds and plants were cultivated in nutrient solutions with single NaCl treatment and NaCl treatment with CaCl2 amendment. By measuring the seed germination rate, plant growth, Na+ and Cl- accumulation in leaves, ion leakage in seedlings and leaves, prompt chlorophyll a fluorescence (PF) transient (OJIP), delayed chlorophyll a fluorescence (DF), and modulated 820 nm reflection (MR) values of the leaves at different growth phases, we observed that Ca2+ alleviated the inhibition of germination and plant growth and decreased Na+ and Cl- accumulation and ion leakage in the leaves under NaCl stress. NaCl stress changed the curves of the OJIP transient, induced PF intensity at P-step (FP) decrease and PF intensity at J-step (FJ) increase, resulted in obvious K and L bands, and altered the performance index of absorption (PIABS), the absorption of antenna chlorophyll (ABS/RC), electron movement efficiency (ETo/TRo), and potential maximum photosynthetic capacity (FV/FM) values. With the time extension of NaCl stress, I1 and I2 in the DF curve showed a decreasing trend, the lowest values of MR/MRO curve increased, and the highest points of the MR/MRO curve decreased. Compared with NaCl treatment, the extent of change induced by NaCl in the values of OJIP, DF and MR was reduced in the NaCl treatment with CaCl2 amendment. These results revealed that Ca2+ might improve the photosynthetic efficiency and the growth of salt-stressed plants by maintaining the integrity of oxygen-evolving complexes and electron transporters on the side of the PSI receptor and enhancing the relationship between the functional units of the photosynthetic electron transport chain. The findings from this study could be used for improving crop productivity in saline alkali lands. | 10.1371/journal.pone.0256529 |
pubmed_1029_13159 | An optically active polymer, poly-beta-hydroxybutyrate (PHB), is produced in cytoplasm of various vacteria. The bending piezoelectric effect was observed in oriented films of PHB. The coefficient between the electrical polarization and the stress gradient was found to be in the order of 10(-18) Cm/N, which was similar to the value reported for bone. Anisotropy in the value of the coefficient was also observed. | 10.3233/bir-1988-251-239 |
pubmed_1140_23440 | A novel O-heteroside, (3RS,4RS)-3,4-dihydroxy-4-(2-hydroxy-5-acetylphenyl)-2-[(beta-O-glucopyranosyl)methyl]-but-1-ene (1), named nauplathizine, and a previously known compound, acetophenone-4-O-glucoside (2), were isolated from the antibacterial acetone extract of the aerial parts of Nauplius aquaticus (L) (Asteraceae, Inulae). The structure of 1 was established via its acetylated derivative by means of spectroscopic and chemical data. | 10.1080/14786410412331302127 |
pubmed_140_7187 | The high mortality rate of lung squamous cell carcinoma (LUSC) is in part due to the lack of early detection of its biomarkers. The identification of key molecules involved in LUSC is therefore required to improve clinical diagnosis and treatment outcomes. The present study used the microarray datasets GSE31552, GSE6044 and GSE12428 from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted to construct the protein-protein interaction network of DEGs and hub genes module using STRING and Cytoscape. The 67 DEGs identified consisted of 42 upregulated genes and 25 downregulated genes. The pathways predicted by KEGG and GO enrichment analyses of DEGs mainly included cell cycle, cell proliferation, glycolysis or gluconeogenesis, and tetrahydrofolate metabolic process. Further analysis of the University of California Santa Cruz and ONCOMINE databases identified 17 hub genes. Overall, the present study demonstrated hub genes that were closely associated with clinical tissue samples of LUSC, and identified TYMS, CCNB2 and RFC4 as potential novel biomarkers of LUSC. The findings of the present study contribute to an improved understanding of the molecular mechanisms of carcinogenesis and progression of LUSC, and assist with the identification of potential diagnostic and therapeutic targets of LUSC. | 10.3892/ol.2019.10873 |
pubmed_159_17802 | Background: The present work aimed to investigate the expression of CD160/ CD200 in CLL and other mature B-cell neoplasms (MBN) and their use as an additional diagnostic tool for differentiating CLL from other MBN. Materials and Methods: Using flow cytometry, we detected the expression of CD160 &CD200 on B-cells from 30 CLL patients, 30 other MBN patients in addition to 20 controls. CDs160/200 measurements were determined as a percentage expression (≥20% was considered positive) and as a ratio of the mean fluorescence intensities (MFIR) of leukemic cells/controls and were considered positive when the ratios were ≥2 and 20, respectively. Results: 90% and 100% of the CLL group expressed CDs160/200 in comparison to 60% and 63.3% of other MBN (p=0.007, p<0.001), respectively. By MFIR, 96.7% and 50% of our CLL group expressed CDs160/200 in comparison to 76.7% and 30% of other MBN, respectively. CDs160/ 200 were not expressed on the controls. Positive co-expression of CD160 and CD200 was found in 90% of the CLL cases, 60% of HCL patients and only in 40% of B-NHL. However, double negative expression of both markers was found only in 24% of the B-NHL patients. Conclusion : CD160 with CD200 can be used as additional diagnostic markers to the available routine panel to differentiate between B-CLL and other non-specified B-NHL patients. | pubmed_159_17802 |
pubmed_487_7473 | We report the first optical recordings of action potentials, in single trials, from one or a few (approximately 1-2 microm) mammalian nerve terminals in an intact in vitro preparation, the mouse neurohypophysis. The measurements used two-photon excitation along the "blue" edge of the two-photon absorption spectrum of di-3-ANEPPDHQ (a fluorescent voltage-sensitive naphthyl styryl-pyridinium dye), and epifluorescence detection, a configuration that is critical for noninvasive recording of electrical activity from intact brains. Single-trial recordings of action potentials exhibited signal-to-noise ratios of approximately 5:1 and fractional fluorescence changes of up to approximately 10%. This method, by virtue of its optical sectioning capability, deep tissue penetration, and efficient epifluorescence detection, offers clear advantages over linear, as well as other nonlinear optical techniques used to monitor voltage changes in localized neuronal regions, and provides an alternative to invasive electrode arrays for studying neuronal systems in vivo. | 10.1152/jn.00929.2007 |
pubmed_422_21190 | The concept of a threshold of activity of a genotoxic agent is primarily based upon considerations of protective mechanisms and multiple cellular targets, which require inactivation before a toxic response is produced. In this paper, we have considered and evaluated the influences of compound metabolism, DNA lesion formation, mutation induction and sequence content, aneuploidy induction and the influence of repair enzymes upon genetic endpoints produced by both DNA reactive chemicals and by those chemicals which modify non-DNA cellular targets. Thresholds of activity have been evaluated by critical analysis of the published literature and original data analysing both the role of sequence context upon point mutation induction and DNA repair mechanisms upon the sensitivity of cultured cells to the induction of aneuploidy. In the case of DNA reactive chemicals, the presence of a threshold of chemical activity will be dependent upon cellular activities such as those of the Phase II enzymes reducing the activity of chemicals before lesion formation takes place and/or those of the DNA repair enzymes which reduce the proportion of DNA lesions which are processed into DNA sequence changes. Under such conditions, a given exposure of a DNA reactive chemical does not produce a linear or semi-linear increase in DNA lesions or in mutation frequency. However, even when these protective mechanisms are overwhelmed by the high exposures of genotoxic chemicals the biological effects of a genotoxin may be influenced by the sequence context of the gene under consideration. Here, we demonstrate that point mutations are detected at relatively higher frequencies in the non-coding introns compared with the coding exons. Many of the base changes detected in the exons do not produce amino acid changes in the proteins coded for by the genes being monitored for mutation induction. Both sequence context and the types of base changes induced may provide a "buffering" effect reducing the biological consequences of mutation induction. Spindle damaging chemicals, such as colcemid and vinblastine, induce aneuploidy by modifying the numbers of spindle fibres which regulate the segregation of chromosomes during mitosis and meiosis. The redundancy of spindle fibres in the dividing mammalian cell leads to the prediction that only chemical exposures which damage most, if not all, of the fibres will lead to the induction of polyploidy and/or aneuploidy. Such predicted thresholds of chemical activity can be observed when both chromosome loss and non-disjunction are measured in wild type cultures. However, we observed a substantial increase in sensitivity to aneugenic chemicals when measurements were made in primary cell cultures derived from xerodoma pigmentosum and trichothiodystrophy patients. Further studies are necessary to evaluate the consequences of the genetic background of tester strains upon the nature of the dose-response curve of aneugenic chemicals. | 10.1016/s1383-5718(99)00166-7 |
pubmed_527_22456 | BACKGROUND
Recently, pattern recognition methods have been deployed in the classification of multiple activation states from mechanomyogram (MMG) signals for the purpose of controlling switching interfaces. Given the propagative properties of MMG signals, it has been suggested that MMG classification should be robust to changes in sensor placement. Nonetheless, this purported robustness remains speculative to date. This study sought to quantify the change in classification accuracy, if any, when a classifier trained with MMG signals from the muscle belly, is subsequently tested with MMG signals from a nearby location.
METHODS
An arrangement of 5 accelerometers was attached to the flexor carpi radialis muscle of 12 able-bodied participants; a reference accelerometer was located over the muscle belly, two peripheral accelerometers were positioned along the muscle's transverse axis and two more were aligned to the muscle's longitudinal axis. Participants performed three classes of muscle activity: wrist flexion, wrist extension and semi-pronation. A collection of time, frequency and time-frequency features were considered and reduced by genetic feature selection. The classifier, trained using features from the reference accelerometer, was tested with signals from the longitudinally and transversally displaced accelerometers.
RESULTS
Classification degradation due to accelerometer displacement was significant for all participants, and showed no consistent trend with the direction of displacement. Further, the displaced accelerometer signals showed task-dependent de-correlations with respect to the reference accelerometer.
CONCLUSIONS
These results indicate that MMG signal features vary with spatial location and that accelerometer displacements of only 1-2 cm cause sufficient feature drift to significantly diminish classification accuracy. This finding emphasizes the importance of consistent sensor placement between MMG classifier training and deployment for accurate control of switching interfaces. | 10.1186/1475-925X-9-23 |
pubmed_733_20349 | BACKGROUND
Most studies investigating steroid allergy have been performed with tixocortol pivalate, hydrocortisone butyrate and budesonide. Betnovate and Dermovate are widely prescribed in the U.K. but little is known about the frequency of sensitization to them.
OBJECTIVES
To determine the optimum method to detect contact allergy to betamethasone valerate (BV) and clobetasol propionate (CP).
METHODS
Seven centres tested consecutive patients attending for investigation of suspected allergic contact dermatitis to these steroids at a range of concentrations in different vehicles.
RESULTS
Of 1562 patients tested, 16 (1%) reacted to either BV or CP. Ten patients (0.7%) reacted to BV and 13 (0.8%) to CP. Two patients of a further centre were included in analysis of dilutions and vehicles. Sixteen of a total of 25 reactions (64%) were identified with a 1% dilution in ethanol.
CONCLUSIONS
Consideration should be given to adding BV and CP to a standard allergy series, given that both are frequently used in the treatment of eczema and that most patients sensitized to them are not identified with currently used markers of steroid allergy. If patch tests to BV and CP are initially negative, but an allergy is suspected, the patient should be further investigated. Further studies are required to identify the ideal patch test material. | 10.1046/j.1365-2133.2002.04816.x |
pubmed_203_19813 | OBJECTIVES
This study was designed to determine the prevalence of peripheral arterial disease (PAD) in candidates for coronary artery bypass grafting (CABG) and to assess the predictive value of different types of subclinical PAD (peripheral occlusive disease and medial arterial calcification [incompressible ankle arteries]).
BACKGROUND
Observational studies report poor prognosis after CABG in the presence of clinical PAD, but data on subclinical PAD are scarce.
METHODS
We prospectively enrolled CABG candidates and measured ankle-brachial index (ABI) preoperatively. Patients were divided into four groups: clinical PAD, subclinical PAD (ABI <0.85), incompressible arteries (ABI >1.5), and no PAD. The primary end point was a composite combining death, acute coronary syndrome, stroke or transient ischemic attack (TIA), and coronary or peripheral revascularization. Secondary end points were overall and cardiovascular death, acute coronary syndrome, and stroke or TIA. Statistical analyses were performed using the Cox regression model.
RESULTS
We consecutively enrolled 1,022 patients (mean age 66.9 +/- 9.2 years). In addition to the 14% with clinical PAD, we detected subclinical PAD in 13% and medial artery calcification in 12%. During an actuarial follow-up of 4.4 years, 81.2% of patients remained event-free. Adverse factors were (p < 0.05) supraventricular arrhythmia (odds ratio [OR] 2.5), ejection fraction <0.40 (OR 2.3), combined valvular surgery (OR 2.5), clinical PAD (OR 3.6), subclinical PAD (OR 3.3), and medial artery calcification (OR 1.9). The latter three factors were also independently predictive for overall and cardiovascular death.
CONCLUSIONS
Beyond clinical PAD, the measurement of ABI before coronary surgery provides substantial information on long-term postoperative prognosis. To our knowledge, this is the first study highlighting the prognostic role of incompressible ankle arteries in secondary prevention. | 10.1016/j.jacc.2005.05.066 |
pubmed_1008_10315 | When viable B6AF1 murine spleen cells were cultured in combination with heat-inactivated B10.D2 spleen cells under appropriate conditions, alloantigen-specific suppressor T cells (Ts) were generated. The optimal conditions for generation of specific Ts included a responder cell number of 2 to 4 X 10(6)/ml, a high stimulator to responder ratio, the use of at least 30 min of heat treatment (45 C) of stimulator cells, and 6 or more days of culture. | 10.1097/00007890-198106000-00009 |
pubmed_293_10952 | BACKGROUND
The growth of sella turcica is completed early in life, therefore it can be used as a stable landmark for the prediction of future skeletal malocclusions. This early diagnosis may help in planning less complicated treatment modalities. Therefore, this study aimed to evaluate the relationship between sella turcica dimensions and morphology with various skeletal patterns.
METHODS
A cross sectional study was conducted using the pre-treatment cephalograms of 180 subjects aged 13-19 years. The subjects were divided into two groups based on skeletal patterns. The dimensions of sella turcica and skeletal patterns were digitally measured using View Pro-X software. One-way ANOVA was applied to compare sella turcica dimensions among skeletal patterns. Sella dimensions and vertical growth patterns were compared using Post-hoc Tukey test. Chi-square test was applied to compare sella morphology among malocclusion groups. Results were taken as statistically significant at p-value of ≤0.05.
RESULTS
Sella dimensions showed insignificant differences among sagittal groups whereas, significant differences were found for sella length (p≤0.02) and depth (p≤0.03) among the vertical groups. Multiple comparisons showed significant differences between sella length (p≤0.03) and diameter (p≤0.04) between normodivergent versus hyperdivergent groups. Moreover, significant differences were found in the sella turcica morphology among sagittal malocclusion (p≤0.03).
CONCLUSIONS
Increased dimensions of sella turcica were associated with hyperdivergent growth pattern. Bridging of the sella turcica was found to be prevalent in class III malocclusion. | pubmed_293_10952 |
pubmed_1048_13862 | A man aged 35 years presented with chronic headache and earache of 1-year duration. He had progressive vision loss and diplopia since last 9 months. He also had pain over the face and episodic profuse epistaxis. On examination, perception of light was absent in the right eye and hand movements were detected at 4 m distance in the left eye. Imaging revealed a lobulated mass in the nasopharynx extending into the bilateral cavernous sinuses and sphenoid sinus with bony erosions. Biopsy of the nasopharyngeal mass revealed pathological features which are characteristic of IgG4 disease. His serum IgG4 levels and acute inflammatory markers were also elevated. The patient was started on oral corticosteroid therapy. Fever, headache and earache resolved early and there was gradual improvement in the vision of the left eye. After 6 months, visual acuity in the left eye was 6/9, but right eye visual acuity had no change. Follow-up imaging revealed a significant reduction in the size of the mass. | 10.1136/bcr-2016-217669 |
pubmed_1136_12018 | BACKGROUND
The prevalence of HIV/hepatitis co-infection in sub-Saharan Africa is not well documented, while both HIV and HBV are endemic in this area.
OBJECTIVE
The aim of this study is to determine the seroprevalence of HBV and HCV virus in HIV-infected subjects in the Gambia.
METHODS
Plasma samples from HIV infected patients (190 individuals with clinically defined AIDS and 382 individuals without AIDS) were tested retrospectively for the presence of HBV sero-markers and for serum HBV DNA, screened for HCV infection by testing for anti-HCV antibody and HCV RNA.
RESULTS
HBsAg prevalence in HIV-positive individuals is 12.2%. HIV/HBV co-infected individuals with CD4 count of <200 cells µL⁻¹ have a higher HBV DNA viral load than patients with higher CD4 count (log 4.0 vs. log 2.0 DNA copies/ml, p < 0.05). Males (OR = 1.8, 95% CI: 1.0, 3.2) were more likely to be HBsAg positive than female. HCV seroprevalence was 0.9% in HIV-positive individuals.
CONCLUSION
The prevalence of HBsAg carriage in HIV- infected Gambians is similar to that obtained in the general population. However co-infected individuals with reduced CD4 levels, indicative of AIDS had higher prevalence of HBeAg retention and elevated HBV DNA levels compared to non-AIDS patients with higher CD4 count. | 10.1186/1743-422X-7-230 |
pubmed_621_4101 | The problem of malaria in adolescence has been surpassed by the immense burden of malaria in children, most especially less than 5. A substantial amount of work done on malaria in pregnancy in endemic regions has not properly considered the adolescence. The present study therefore aimed at evaluating the prevalence of Plasmodium falciparum and anaemia infection in adolescent pregnant girls in the Sekondi-Takoradi metropolis, Ghana. The study was carried out at four hospitals in the Sekondi-Takoradi metropolis of the western region of Ghana from January 2010 to October 2010. Structured questionnaires were administered to the consenting pregnant women during their antenatal care visits. Information on education, age, gravidae, occupation and socio-demographic characteristics were recorded. Venous bloods were screened for malaria using RAPID response antibody kit and Geimsa staining while haemoglobin estimations were done by cyanmethemoglobin method. The results revealed that adolescent pregnant girls were more likely to have malaria infection than the adult pregnant women (34.6% verses 21.3%, adjusted OR 1.65, 95% CI, 1.03-2.65, P=0.039). In addition, adolescent pregnant girls had higher odds of anaemia than their adult pregnant women equivalent (43.9% versus 33.2%; adjusted OR 1.63, 95% CI, 1.01-2.62, P=0.046). Taken together, these data suggest that adolescent pregnant girls were more likely to have malaria and anaemia compared to their adult pregnant counterpart. Results from this study shows that proactive adolescent friendly policies and control programmes for malaria and anaemia are needed in this region in order to protect this vulnerable group of pregnant women. | 10.1016/j.actatropica.2012.05.014 |
pubmed_635_10692 | The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na(+)/H(+) exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the -61 to -42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. | pubmed_635_10692 |
pubmed_241_7332 | BACKGROUND
The impact of matrix metalloproteinase (MMP) on left ventricular (LV) remodeling and heart failure events is unresolved in patients with hypertrophic cardiomyopathy (HCM).
METHODS AND RESULTS
Plasma levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and clinical findings and heart failure events were evaluated in 41 HCM patients, including 8 with LV systolic impairment. Plasma B-type natriuretic peptide (BNP) levels were also measured. MMP-2 levels in patients with severe symptoms were higher than that in those with no or mild symptoms. The levels of MMP-2 and TIMP-1 were positively related to LV end-systolic and left atrial dimensions, and inversely related to LV ejection fraction. MMP-2 levels were positively related to BNP levels (r=0.52, P=0.0009). However, MMP-9 levels were not related to echocardiographic parameters and plasma BNP levels. Six patients had complicated heart failure events during the follow-up period of 3.2+/-0.7 years. Patients with high plasma MMP-2 levels (>1,170 ng/ml) revealed a poorer prognosis than those with low MMP-2 levels.
CONCLUSIONS
Elevated levels of MMP-2 were related to LV remodeling and poor prognosis in patients with HCM. These results suggest that regulation of the extracellular collagen matrix might be one of the therapeutic targets in patients with HCM. | 10.1253/circj.cj-09-1013 |
pubmed_990_20893 | OBJECTIVE
We investigate a knowledge-based help system for developers of an integrated clinical information system (CIS). The first objective in the study was to determine the system's ability to answer users' questions effectively. User performance and behavior were studied. The second objective was to evaluate the effect of using questions and answers to augment or replace traditional program documentation.
DESIGN
A comparative study of user and system effectiveness using a collection of 47 veritable questions regarding the CIS, solicited from various CIS developers, is conducted. Most questions were concerning the clinical data model and acquiring the data.
MEASUREMENTS
Answers using current documentation known by users were compared to answers found using the help system. Answers existing within traditional documentation were compared to answers existing within question-answer exchanges (Q-A's).
RESULTS
The support system augmented 39% of users' answers to test questions. Though the Q-A's were less than 5% of the total documentation collected, these files contained answers to nearly 50% of the questions in the test group. The rest of the documentation contained about 75% of the answers.
CONCLUSIONS
A knowledge-based help system built by collecting questions and answers can be a viable alternative to large documentation files, providing the questions and answers can be collected effectively. | 10.1006/cbmr.1998.1470 |
pubmed_824_12648 | The question how wisdom can best be measured is still open to debate. Currently, there are two groups of wisdom measures: open-ended performance measures and self-report measures. This overview article describes the most popular current measures of wisdom: the Berlin Wisdom Paradigm, the Bremen Wisdom Paradigm, Grossmann's wise-reasoning approach, the Three-Dimensional Wisdom Scale, the Self-Assessed Wisdom Scale, and the Adult Self-Transcendence Inventory. It discusses the specific challenges of both open-ended and self-report approaches with respect to content validity, convergent and divergent validity, concurrent and discriminant validity, and ecological validity. Finally, promising new developments are outlined that may bridge the gap between wisdom as a competence and wisdom as an attitude and increase ecological validity by being more similar to real-life manifestations of wisdom. These new developments include autobiographical approaches and advice-giving paradigms. | 10.1093/geronb/gbx140 |
pubmed_834_14249 | We studied the immunohistochemical localization of cathepsin E (cath E) in the brains of patients with Alzheimer disease (AD) and control brains. In the normal brain cathepsin E immunoreactivity was detectable in a small number (below 5%) of neocortical and hippocampal neurons. In AD brains cathepsin E antigen was revealed in most large cortical and hippocampal pyramids and in neurons of the Nuc. basalis of Meynert. Cathepsin E was also present in cerebral microvessels, microglia, and in senile plaques. The enzyme might play roles in the process of neurodegeneration taking place in AD. | 10.1016/0006-8993(94)91509-1 |
pubmed_741_13599 | The effects of using picture prompts on the acquisition, generalization, and maintenance of complex vocational tasks were evaluated within a multiple baseline design across subjects and tasks. Five moderately and severely mentally retarded adolescents were first trained to use picture prompts to guide their performance on one or more complex tasks. Following training, posttesting with and without the picture prompts was conducted to evaluate the effects of training and to determine maintenance effects over a 2- to 4-week interval. Generalization of performance across tasks was assessed with three of the students who were provided novel tasks (with and without picture prompts) without training. Results indicated that picture prompts can be successfully used to promote both acquisition and generalization of performance, and that subsequent training time on a novel task was reduced when the use of picture prompts had been previously trained. | 10.1901/jaba.1983.16-417 |
pubmed_483_10489 | Infections due to adenovirus, polyomaviruses (BK and JC viruses), and parvovirus B19 may not be as common as infections due to other DNA viruses, such as cytomegalovirus in patients with hematological malignancies and the recipients of hematopoietic stem cell transplantation. However, these infections may result in life-threatening diseases that significantly impact patients' recovery, morbidity, and mortality. Treating physicians should be aware of the diseases associated with these viruses, the patient populations at increased risk for complications due to these infections, and the available diagnostic and therapeutic approaches. | 10.1016/j.idc.2019.02.005 |
pubmed_1100_11253 | Previous studies have suggested an involvement of enkephalins in regulation of oxytocin (OXT) and vasopressin (AVP) release, which seems to disagree with the very low affinities of Met- and Leu-enkephalin for the kappa opioid receptor. As opioid receptors in the neural lobe exclusively exist of kappa receptors, we studied the binding characteristics of larger pro-enkephalin derived peptides for opioid binding sites in the neural lobe by means of light microscopic receptor autoradiography. In addition, the pharmacological characteristics of opioid binding sites in the neural lobe were compared with those in other parts of the pituitary. In the neural as well as the intermediate lobe both high and low affinity 3H-bremazocine binding sites were present. Binding to these sites was completely displaceable by both naloxone and nor-binaltorphimine suggesting that these sites represent kappa opioid receptors. Also with regard to selectivity and affinity characteristics to other ligands, opioid binding sites in the neural and intermediate lobe were quite similar. In the anterior lobe a very low level of bremazocine binding was present, which could not be displaced by nor-binaltorphimine. Displacement studies with pro-enkephalin and pro-dynorphin derived peptides showed that both groups of peptides could bind to opioid binding sites in the neural and intermediate lobe. Especially the relatively large pro-dynorphin and pro-enkephalin derived peptides, such as dynorphin 1-17 and BAM22, appeared to be very potent ligands for these opioid binding sites and were much more potent than smaller fragments, such as dynorphin 1-8, and Met- and Leu-enkephalin. These results contradict the existence of a mismatch in the neural (and intermediate) lobe with regard to the local type of opioid peptides and receptors present. | 10.1111/j.1365-2826.1994.tb00554.x |
pubmed_626_12919 | Nitrogenase catalyzes the six electron/six proton reduction of N2 to two ammonia molecules at a complex organometallocluster called "FeMo cofactor." This cofactor is buried within the alpha-subunit of the MoFe protein, with no obvious access for substrates. Examination of high-resolution X-ray crystal structures of MoFe proteins from several organisms has revealed the existence of a water-filled channel that extends from the solvent-exposed surface to a specific face of FeMo cofactor. This channel could provide a pathway for substrate and product access to the active site. In the present work, we examine this possibility by substituting four different amino acids that line the channel with other residues and analyze the impact of these substitutions on substrate reduction kinetic parameters. Each of the MoFe protein variants was purified and kinetic parameters were established for the reduction of the substrates N2, acetylene, azide, and propyne. For each MoFe protein, V (max) values for the different substrates were found to be nearly unchanged when compared with the values for the wild-type MoFe protein, indicating that electron delivery to the active site is not compromised by the various substitutions. In contrast, the K(m) values for these substrates were found to increase significantly (up to 22-fold) in some of the MoFe protein variants compared with the wild-type MoFe protein values. Given that each of the amino acids that were substituted is remote from the active site, these results are consistent with the water-filled channel functioning as a substrate channel in the MoFe protein. | 10.1007/s00775-009-0544-2 |
pubmed_583_7599 | Long-term changes of synaptic plasticity depend on protein synthesis and transcription. Ng (neurogranin) is a small protein concentrated at dendrites and spines of forebrain neurons, involved in synaptic plasticity through the regulation of CaM (calmodulin)-mediated signalling. Ng presents a central IQ motif that mediates its binding to CaM and PA (phosphatidic acid) and that can be phosphorylated by PKC (protein kinase C). In the present manuscript, we report that Ng displays a strong nuclear localization when expressed in cell lines and hippocampal neurons, either alone or fused to GFP (green fluorescent protein; GFP-Ng). Furthermore, using subcellular fractionation and immunocytochemical techniques, we were able to localize endogenous Ng in the nuclei of rat forebrain neurons. Nuclear localization of Ng depends on its IQ motif and is reduced by binding to cytoplasmic CaM. Also, PKC stimulation induces a transient nuclear translocation of Ng in acute hippocampal slices. A similar translocation is observed in the neurons of the cerebral cortex and hippocampus after the induction of generalized seizures in adult rats. In summary, the results of the present study show that a fraction of rat brain Ng is localized in the neuronal nuclei and that synaptic activity regulates its translocation from the cytoplasm. The possible involvement of Ng in the regulation of intranuclear Ca2+/CaM-dependent signalling and gene expression is discussed. | 10.1042/BJ20091071 |
pubmed_552_11057 | Following a large earthquake in Nepal, the experience of a small hospital in dealing with the resulting mass casualties is described. The value of pre-planning and effective triage of the injured is stressed, and aspects of surgical and medical care specific to earthquake victims discussed. Clinical and administrative challenges encountered in mounting a major relief exercise in a Third World setting are also described. frequent exercising of military hospitals and personnel in handling mass casualties is an applicable to civilian natural catastrophies as to battlefield medical support. | 10.1136/jramc-136-01-02 |
pubmed_554_23395 | BACKGROUND
Computed tomography (CT)-guided cervical nerve injections are broadly being used in the treatment of cervical radiculopathy; however, catastrophic complications have been reported. Herein, we aimed to evaluate the efficacy, feasibility, and safety of a novel CT-guided cervical injection technique.
MATERIALS AND METHODS
We prospectively performed cervical injections in 28 patients with cervical radiculopathies using a novel CT-guided cervical transforaminal injection technique; lateral peri-isthmic approach in which the tip of the needle advanced to the lateral cortex of the isthmus instead of the foraminal area. Patients' pain reduction rates were evaluated using visual analog scores (VAS) at pre-treatment, immediately after treatment, at 3 weeks and 6 months after the treatment. Intra-vascular contrast medium injections and distribution of the contrast material into the foraminal, epidural or extraforaminal area during the procedure were noted.
RESULTS
Pre-treatment pain scores were reduced by 4.2 ± 1.4 (p < 0.001), 3.9 ± 1.37 (p < 0.001) and 3.25 ± 1.53 (p < 0.001) immediately after the treatment, 3 weeks and 6 months after the treatment respectively. The number of patients with >50% pain relief as measured by VAS were 21 (75%) immediately after the procedure, 19 (67.8%) at 3 weeks and 17 (60%) at 6 months after the procedure. The injected contrast material was dispersed into the neural foramen in 9 cases (32.1%), the foraminal and epidural area in 14 cases (50%) and the extraforaminal area in 5 cases (17.9%).
CONCLUSION
The CT-guided lateral peri-isthmic approach seems to be a secure and feasible method for cervical injections with satisfactory pain reduction. | 10.1007/s00256-018-2986-5 |
pubmed_1088_19744 | Sympathetic activation in chronic heart failure (CHF) is greatly augmented at rest but the response to exercise remains controversial. We previously demonstrated that single-unit muscle sympathetic nerve activity (MSNA) provides a more detailed description of the sympathetic response to physiological stress than multi-unit nerve recordings. The purpose of this study was to determine whether the reflex response and discharge properties of single-unit MSNA are altered during handgrip exercise (HG, 30% of maximum voluntary contraction for 3 min) in CHF patients (New York Heart Association functional class II or III, n = 16) compared with age-matched healthy control subjects (n = 13). At rest, both single-unit and multi-unit indices of sympathetic outflow were augmented in CHF compared with controls (P < 0.05). However, the percentage of cardiac intervals that contained one, two, three or four single-unit spikes were not different between the groups. Compared to the control group, HG elicited a larger increase in multi-unit total MSNA (Delta1002 +/- 50 compared with Delta636 +/- 76 units min(-1), P < 0.05) and single-unit MSNA spike incidence (Delta27 +/- 5 compared with Delta8 +/- 2 spikes (100 heart beats)(-1)), P < 0.01) in the CHF patients. More importantly, the percentage of cardiac intervals that contained two or three single-unit spikes was increased (P < 0.05) during exercise in the CHF group only (Delta8 +/- 2% and Delta5 +/- 1% for two and three spikes, respectively). These results suggest that the larger multi-unit total MSNA response observed during HG in CHF is brought about in part by an increase in the probability of multiple firing of single-unit sympathetic neurones. | 10.1113/jphysiol.2009.172627 |
pubmed_401_7918 | Limestone of different particle sizes is often calcined together to improve production efficiency, but the calcination effect of mixed particle size limestone is difficult to guarantee. To investigate the effect of different particle size combinations on calcination, this study uses a porous media model and a shrinking core model to simulate the calcination process for a single particle size and two mixed particle sizes in a Parallel Flow Regenerative lime kiln (PFR lime kiln). The results of the study show that an increase in void fraction has a small effect on the gas temperature. The temperature also does not change with particle sizes. At the same time, the decomposition is poor near the wall and better the closer to the center of the calcination zone. In addition, when the particle sizes differ by 2 times, the decomposition of small limestone particles had less influence, and the decomposition of large particles was also better. When the particle sizes differ by 3 times, the decomposition of both limestone sizes is more affected, especially for the larger limestone size, where only the outer surface is involved in the decomposition. | 10.3390/ma15134609 |
pubmed_347_14336 | Presented in the article is a rare clinical case report concerning successful treatment of a female patient with vaginal paraganglioma of the neck - a tumour extending from the level of the trunk of the common carotid artery in cranial direction to the base of the skull. Mentioned are difficulties of carrying out an operational intervention requiring the use of certain surgical techniques. The tumour was removed as a single block with the involvement into the process of the major vessels of the neck and nervous formations. The reconstructive operation performed was common carotid - internal carotid prosthetic repair with a 6.3-4.5 mm cone-shape prosthesis 'Gore-tex' on the right. | pubmed_347_14336 |
pubmed_1014_4756 | Principal meridians of the corneal vertex of the human ocular system are not always orthogonal. To study these irregular surfaces at the vertex, which have principal meridians with an angle different from 90°, we attempt to define so-called parastigmatic surfaces; these surfaces allow us to correct several classes of irregular astigmatism, with nonorthogonal principal meridians, using a simple refractive surface. We will create a canonical surface to describe the surfaces of the human cornea with a short and simple formula, using two additional parameters to the current prescription: the angle between principal meridians and parharmonic variation of curvatures between them. | 10.1364/AO.53.003438 |
pubmed_177_21945 | A single word, Epigenetics, underlies one exciting subject in today's Science, with different sides and with interactions with philosophy. The apparent trivial description includes everything in between genotype and phenotype that occurs for a given unique DNA sequence/genome. This Perspective article first presents an historical overview and the reasons for the lack of consensus in the field, which derives from different interpretations of the diverse operative definitions of Epigenetics. In an attempt to reconcile the different views, we propose a novel concept, the "cytocrin system." Secondly, the article questions the inheritability requirement and makes emphasis in the epigenetic mechanisms, known or to be discovered, that provide hope for combating human diseases. Hopes in cancer are at present in deep need of deciphering mechanisms to support ad hoc therapeutic approaches. Better perspectives are for diseases of the central nervous system, in particular to combat neurodegeneration and/or cognitive deficits in Alzheimer's disease. Neurons are post-mitotic cells and, therefore, epigenetic targets to prevent neurodegeneration should operate in non-dividing diseased cells. Accordingly, epigenetic-based human therapy may not need to count much on transmissible potential. | 10.3389/fgene.2017.00179 |
pubmed_548_5973 | BACKGROUND
It is common for patients who die from subarachnoid hemorrhage to have a focus on comfort measures at the end of life. The potential role of ethnicity in end-of-life decisions after brain injury has not been extensively studied.
METHODS
Patients with subarachnoid hemorrhage were prospectively followed in an observational database. Demographic information including ethnicity was collected from medical records and self-reported by patients or their family. Significant in-hospital events including do-not-resuscitate orders, comfort measures only orders (CMO; care withheld or withdrawn), and mortality were recorded prospectively.
RESULTS
1255 patients were included in our analysis: 650 (52 %) were White, 387 (31 %) Hispanic, and 218 (17 %) Black. Mortality was similar between the groups. CMO was more commonly observed in Whites (14 %) compared to either Blacks (10 %) or Hispanics (9 %) (p = 0.04). In a multivariate analysis controlling for age and Hunt-Hess grade, Hispanics were less likely to have CMO than Whites (OR, 0.6; 95 %CI, 0.4-0.9; p = 0.02). Of the 229 patients who died, 77 % of Whites had CMO compared to 54 % of Blacks and 49 % of Hispanics (p < 0.01). In a multivariate analysis, Blacks (OR, 0.3; 95 %CI, 0.2-0.7; p < 0.01) and Hispanics (OR, 0.3; 95 %CI, 0.2-0.6; p < 0.01) were less likely to die with CMO orders than Whites.
CONCLUSION
After subarachnoid hemorrhage, Blacks and Hispanics are less likely to die with CMO orders than Whites. Further research to confirm and investigate the causes of these ethnic differences should be performed. | 10.1007/s12028-014-0073-x |
pubmed_305_20270 | Increased perivascular fat mass contributes to cardiometabolic risk (CMR). High peribrachial adipose tissue (PBAT) associates with insulin resistance independently of established CMR parameters. It is unknown to what extent periaortic adipose tissue (PAAT) may have a similar impact. In 95 participants, precise quantification of total adipose tissue, PBAT, PAAT, visceral adipose tissue (VAT), and liver fat (LF) content was performed by whole-body magnetic resonance imaging. Insulin sensitivity was determined by oral glucose tolerance test and carotid intima-media thickness (cIMT) by high-resolution ultrasound. In univariate analyses, PAAT correlated with PBAT (β = .65, P < .0001). A negative correlation of PAAT (β = -.35, P = .0002) and PBAT (β = -.43, P < .0001) with insulin sensitivity was observed. While in a stepwise forward regression analysis the relationship of PAAT with insulin sensitivity was no longer significant after adjustment for VAT, LF content, and other CMR factors ( P = 0.42), PBAT still correlated with insulin sensitivity ( r2 = .35, P = .01). The association between PAAT and cIMT (β = .49, P < .0001) remained significant after adjustment for these variables ( r2 = .42, P = .0001). Although PAAT and PBAT strongly correlate, PAAT is not associated with insulin resistance, but with cIMT. Therefore, PAAT and PBAT may act differently as possible modulators of insulin resistance and subclinical atherosclerosis. | 10.1177/0003319718755581 |
pubmed_591_5924 | New York City has had a long history of implementing local policies to reduce air pollution. Enacted as a part of PlaNYC, the Clean Heat policies aim to lower wintertime ambient air pollution by phasing out dirty No. 6 heating fuel oil and transitioning to comparatively cleaner No. 4, No. 2, or natural gas. This study evaluates the impacts of policies on ambient air pollution and, given that people spend the majority of their time inside, importantly, indoor air pollution. Using a natural experiment, we evaluate the effects of the policies by measuring average two-week levels of indoor and outdoor black carbon (BC) and fine particulate matter (PM2.5) in 48 upper Manhattan apartments in successive winter heating seasons before and after mandated fuel transition. We failed to observe systematic improvements in indoor BC and PM2.5 concentrations in follow-up. However, outdoor levels of PM2.5 did improve, with statistical differences observed among buildings converting to the cleanest fuels. Non-statistical improvements were observed for outdoor BC. However, when accounting for meteorological differences, apartment characteristics, and behavioral patterns that may have influenced air pollution measurements, these differences were not significant. The study results have important policy and equity implications considering the differential improvements in air quality by conversion to No. 4 oil as compared to the cleaner No. 2 oil and natural gas. | 10.1371/journal.pone.0199783 |
pubmed_588_3511 | The authors examined gender differences and the influence of intelligence quotient (IQ) test experience in the self and partner estimation of H. Gardner's (1999) 10 multiple intelligences. Portuguese students (N = 190) completed a brief questionnaire developed on the basis of an instrument used in previous research (A. Furnham, 2001). Three of the 10 self-estimates yielded significant gender differences. Men believed they were more intelligent than were women on mathematical (logical), spatial, and naturalistic intelligence. Those who had previously completed an IQ test gave higher self-estimates on 2 of the 10 estimates. Factor analysis of the 10 and then 8 self-estimated scores did not confirm Gardner's 3-factor classification of multiple intelligences in this sample. | 10.3200/JRLP.140.6.591-602 |
pubmed_1110_18412 | Necrotizing soft tissue infections are characterized clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality. Accurate diagnosis and appropriate treatment must include early surgical intervention and antibiotic therapy. Mortality rate is very high and could be even higher in an immunocompromised host. We present a 57-year-old female with history of rheumatoid arthritis on oral corticosteroid and methotrexate therapy with painful swelling of the left hand following a cat bite that was diagnosed as having group A streptococcus pyogenes-associated necrotizing fasciitis. Treatment with ampicillin-sulbactam, Clindamycin, and surgical debridement was performed. In spite of all the adequate therapy she succumbed to death from streptococcal toxic shock and related complications after thirty-two days of treatment in intensive care unit. Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. Tissue infections in cat bite wounds are commonly caused by pathogenic bacterium known as Pasteurella multocida. Group A streptococcal infections are not reported following cat bites. A high index of suspicion must be maintained to suspect group A streptococcal associated necrotizing fasciitis following cat bites and an early medical and surgical intervention should be made for any best possible outcome. | 10.1155/2017/3718360 |
pubmed_1037_26114 | BACKGROUND
Postoperative adhesions are a potentially life-threatening complication of abdominal surgery. We previously showed that substance P (SP), acting through the neurokinin-1 receptor (NK-1R), is an important early mediator of adhesiogenesis through its regulation of the tissue plasminogen activator/plasminogen activator inhibitor-1 (PAI-1) fibrinolytic system. SP also mediates neurogenic inflammation by recruiting inflammatory leukocytes, such as neutrophils and macrophages. Our objective was to determine the role of SP-dependent chemotactic recruitment of these inflammatory cells through the CXCR2 in postsurgical adhesion formation.
MATERIALS AND METHODS
A mouse cecal cauterization model was used to generate intra-abdominal adhesions. Protein and mRNA levels of the chemokines CXCL1 and CXCL2 and their receptor CXCR2 were measured at 3 h and 6 h after surgery in peritoneal tissue and in peritoneal lavages in response to antagonists for the SP receptor and CXCR2, and in IFN-γ knockout mice.
RESULTS
Postsurgical adhesion formation was inhibited by both an antagonist to NK-1R and an antagonist to CXCR2. Expression levels of neutrophil chemokines and CXCR2 in peritoneal tissue peaked 3-6 h after surgery and partially depended on SP and IFN-γ, one of its downstream mediators. An NK-1R antagonist inhibited SP-mediated increases in the expression of the PAI-1 inhibitory component of the fibrinolytic system, but the CXCR2 antagonist had no effect.
CONCLUSIONS
Postsurgical adhesiogenesis involves upregulation of chemokine signaling that is partially SP- and IFN-γ-dependent. However, the adhesiogenic properties of chemokine signaling are not mediated through the inhibition of fibrinolysis with PAI-1, as was previously shown for SP. | 10.1016/j.jss.2021.08.038 |
pubmed_1114_20131 | BACKGROUND
The expression of acetylcholinesterase (AChE) could be induced during apoptosis in various cell types. And reduced AChE expression either by siRNA could prevent apoptosis. However, the detailed mechanisms underlying the AChE regulation are largely unknown in human breast cancer cell.
MATERIAL AND METHODS
MCF-7 cells were cultured and treated by cisplatin in the absence or presence of p53 siRNA.
RESULTS
In this study, the regulation of AChE expression during apoptosis induced by cisplatin, a current used anticancer drug, was investigated in human breast cancer cell line MCF-7. Exposure of MCF-7 cells to cisplatin resulted in apoptosis in a time- and concentration-dependent manner. Meanwhile, the upregulated AChE and p53 were also observed during apoptosis. Silencing interfering RNA directed against p53 blocked the expression of AChE.
CONCLUSION
Taken together, these results suggested that AChE expression could be upregulated by the activation of p53 during apoptosis induced by cisplatin in MCF-7 cells. | 10.7150/jca.10521 |
pubmed_631_17147 | To adapt to changes in environmental conditions, bacteria regulate their gene expression at the transcriptional but also at the post-transcriptional level, e.g. by small RNAs (sRNAs) which modulate mRNA stability and translation. The conserved RNA chaperone Hfq mediates the interaction of many sRNAs with their target mRNAs, thereby playing a global role in fine-tuning protein production. In this study, we investigated the significance of Hfq for the enteropathogen Yersina enterocolitica serotype O:8. Hfq facilitated optimal growth in complex and minimal media. Our comparative protein analysis of parental and hfq-negative strains suggested that Hfq promotes lipid metabolism and transport, cell redox homeostasis, mRNA translation and ATP synthesis, and negatively affects carbon and nitrogen metabolism, transport of siderophore and peptides and tRNA synthesis. Accordingly, biochemical tests indicated that Hfq represses ornithine decarboxylase activity, indole production and utilization of glucose, mannitol, inositol and 1,2-propanediol. Moreover, Hfq repressed production of the siderophore yersiniabactin and its outer membrane receptor FyuA. In contrast, hfq mutants exhibited reduced urease production. Finally, strains lacking hfq were more susceptible to acidic pH and oxidative stress. Unlike previous reports in other Gram-negative bacteria, Hfq was dispensable for type III secretion encoded by the virulence plasmid. Using a chromosomally encoded FLAG-tagged Hfq, we observed increased production of Hfq-FLAG in late exponential and stationary phases. Overall, Hfq has a profound effect on metabolism, resistance to stress and modulates the production of two virulence factors in Y. enterocolitica, namely urease and yersiniabactin. | 10.1371/journal.pone.0086113 |
pubmed_1094_6550 | Safer conception interventions reduce HIV incidence while supporting the reproductive goals of people living with or affected by HIV. We developed a consensus statement to address demand, summarize science, identify information gaps, outline research and policy priorities, and advocate for safer conception services. This statement emerged from a process incorporating consultation from meetings, literature, and key stakeholders. Three co-authors developed an outline which was discussed and modified with co-authors, working group members, and additional clinical, policy, and community experts in safer conception, HIV, and fertility. Co-authors and working group members developed and approved the final manuscript. Consensus across themes of demand, safer conception strategies, and implementation were identified. There is demand for safer conception services. Access is limited by stigma towards PLWH having children and limits to provider knowledge. Efficacy, effectiveness, safety, and acceptability data support a range of safer conception strategies including ART, PrEP, limiting condomless sex to peak fertility, home insemination, male circumcision, STI treatment, couples-based HIV testing, semen processing, and fertility care. Lack of guidelines and training limit implementation. Key outstanding questions within each theme are identified. Consumer demand, scientific data, and global goals to reduce HIV incidence support safer conception service implementation. We recommend that providers offer services to HIV-affected men and women, and program administrators integrate safer conception care into HIV and reproductive health programs. Answers to outstanding questions will refine services but should not hinder steps to empower people to adopt safer conception strategies to meet reproductive goals. | 10.1007/s10461-017-1777-7 |
pubmed_332_9139 | Gene expression measurements with quantitative real-time polymerase chain reaction (PCR) have a major hindrance of not directly measuring RNA and, thus, needing a reverse transcription (RT) step to first produce complementary DNA (cDNA). However, few studies have assessed the robustness of the RT step, and almost none has compared the factual performance of RT and real-time PCR enzymes. Here, we examined the variability of RT and PCR reactions and compared enzyme reproducibility by reverse transcribing identical RNA with eight RT enzymes and then amplifying the cDNA produced by one of them with six real-time PCR enzymes. The same four reference genes were measured in both experiments, and the data were analyzed with Bayesian multilevel models. Reproducibility and the efficiency of the RT enzymes, excluding one, varied moderately, but RT was always less precise than PCR; four PCR enzymes performed in an excellent manner. The transcription efficiencies of two of the measured reference genes (Actb and Sdha) lacked covariance with the general RT efficiency and showed poor reproducibility. In conclusion, most variation in quantitative real-time RT-PCR (RT-qPCR) emanates from the RT phase, and gene-related factors seem to be the primary determinants of this variation, discouraging the use of control genes in RT-qPCR normalization without prior information of their RT robustness. | 10.1016/j.ab.2012.06.010 |
pubmed_705_11541 | It is well known that exposure of cells to heat leads to a drastic inhibition of DNA synthesis as assayed in vivo by the incorporation of radioactive precursors into acid-insoluble material. Here we introduce an SV40 in vitro DNA replication assay and show that this inhibition may be partly due to the activation of a checkpoint in S phase that stalls the initiation of DNA replication by inactivating replication protein A (RPA), an essential factor for replication. The results implicate trans-acting processes in the regulation of DNA replication after heat exposure and suggest that such processes may be an integral part of the normal response to heat insult. The observations extend and complement previous studies that have implicated heat-induced chromatin damage acting in cis as a cause for the observed inhibition of DNA synthesis in cells exposed to hyperthermia. A model is proposed postulating that the presence of single-stranded DNA, or heat-induced damage to chromatin structures directly, albeit passively, inhibits the elongation stages of ongoing DNA replication. It is hypothesized that arrested replication forks subsequently act as signals to activate the S-phase checkpoint that actively inhibits the initiation of new replicons. The ultimate purpose of this response will be the minimization of the toxic consequences of heat-induced damage, as it may delay DNA replication until chromatin conformation has been restored. DNA replication in the presence of chromatin damage has been implicated in the formation of lethal chromosome aberrations observed in cells heated during S phase. The operation of active processes in the regulation of DNA replication in cells exposed to hyperthermia offers new targets for intervention and sensitization of cells to heat. | pubmed_705_11541 |
pubmed_135_24197 | Specimen identification is the backbone of archeozoological research. The challenge of differentiating postcranial skeletal elements of closely related wild animals in biodiverse regions can prove a barrier to understanding past human foraging behaviours. Morphometrics are increasingly being employed to classify paleozoological animal remains, however, the potential of these methods to discriminate between wild animal groups has yet to be fully realised. Here we demonstrate the applicability of a traditional morphometric approach to taxonomically classify foot and ankle bones of kangaroos, a large and highly diverse marsupial family. Using multiple discriminant analysis, we classify archaeological specimens from Boodie Cave, in northwest Australia and identify the presence of two locally extinct macropod species during the terminal Pleistocene. The appearance of the banded hare-wallaby and northern nail-tail wallaby in the Pilbara region at this time provides independent evidence of the ecological and human responses to a changing climate at the end of the last Ice Age. Traditional morphometrics provides an accessible, inexpensive, and non-destructive tool for paleozoological specimen classification and has substantial potential for applications to other diverse wild faunas. | 10.1038/s41598-022-21021-w |
pubmed_611_21032 | OBJECTIVES
Tranexamic acid (t-AMCA) has been shown to cause severe convulsions in humans and cats when applied topically to the central nervous system. We wanted to determine whether pure t-AMCA or fibrin sealant (FS) containing t-AMCA would induce similar effects when applied to the spinal cord in a rat model.
METHODS
Following low-thoracic laminectomy, the dura was incised to expose the dorsal surface of the lumbar enlargement. Rats were allocated to one of the following treatments: 1) t-AMCA (10 mg/ml), 2) vehicle (phosphate buffered saline), 3) FS containing t-AMCA, 4) FS containing aprotinin. The response of the rats was evaluated based on neurological and behavioral observations. Additionally, motor function was scored in the rats that had received FS.
RESULTS
Application of either 10 mg/ml t-AMCA or FS containing t-AMCA caused severe hind limb spasms that developed into spontaneous generalized convulsions. Two of the three rats that had received FS containing t-AMCA died of respiratory failure. In contrast, application of vehicle or FS containing aprotinin did not cause any abnormal conditions of the animals.
CONCLUSION
Tranexamic acid may cause severe complications when used in the central nervous system. Thus, fibrin sealants containing t-AMCA should not be used in neurosurgery. | pubmed_611_21032 |
pubmed_349_8262 | The small molecule multi-kinase inhibitor sorafenib has become the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC) and renal cell carcinoma. Similar to other kinase inhibitors, drug resistance hinders its clinical use; thus, combination therapy to improve sorafenib sensitivity is a promising approach. The present study shows for the first time that the combination of sorafenib and wogonin exerts a significant potentiation of cytotoxicity in a number of human HCC cell lines in a dose-dependent manner. Enhanced cell death was due to potentiation of apoptosis, which was demonstrated by increased apoptotic cell populations, caspase activation and suppression of cell death by the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl. Sorafenib induced autophagy activation, which was shown by autophagic flux. Suppression of autophagy with the autophagy inhibitors chloroquine or 3-methyladenine significantly enhanced cytotoxicity, suggesting that sorafenib-induced autophagy is cytoprotective. Notably, wogonin effectively inhibited sorafenib-induced autophagy. Altogether, our results indicate that the combination of wogonin and sorafenib effectively kills human HCC cells. This occurs, at least in part, through autophagy inhibition, which potentiates apoptosis. Thus, wogonin could be an ideal candidate for increasing sorafenibs activity in HCC therapy, which warrants further investigation in vivo. | 10.3892/ol.2017.6059 |
pubmed_300_2020 | BACKGROUND
The purpose of this study was to assess the between-day reliability of the electromechanical delay (EMD) of selected neck muscles during the performance of maximal isometric contractions in five different directions.
METHODS
Twenty-one physically active males participated in two testing sessions separated by seven to eight days. Using a custom-made fixed frame dynamometer, cervical force and surface electromyography (EMG) were recorded bilaterally from the splenius capitis, upper trapezius and sternocleidomastoid muscles during the performance of efforts in extension, flexion, left and right lateral bending, and protraction. The EMD was extracted using the Teager-Kaiser Energy Operator. Reliability indices calculated for each muscle in each testing direction were: the difference in scores between the two testing sessions and corresponding 95% confidence intervals, the standard error of measurement (SEM) and intra-class correlation coefficients (ICC).
RESULTS
EMD values showed no evidence of systematic difference between the two testing sessions across all muscles and testing directions. The SEM for extension, flexion and lateral bending efforts ranged between 2.5 ms to 4.8 ms, indicating a good level of measurement precision. For protraction, SEM values were higher and considered to be imprecise for research and clinical purposes. ICC values for all muscles across all testing directions ranged from 0.23 to 0.79.
CONCLUSION
EMD of selected neck muscles can be measured with sufficient precision for the assessment of neck muscle function in an athletic population in the majority of directions tested. | 10.1186/1758-2555-1-22 |
pubmed_661_14577 | A geneticist's view on the origin of life would focus on individual nucleic acid molecules rather than on their concentrations, on stochastics rather than on differential equations. The 'package model' envisages primordial compartments that contain ensembles of primordial genes. These are replicated independently from each other. During package fission they are distributed to two daughter packages. Packages with a complete ensemble of genes can continue to propagate. However, mutations as well as the stochastic nature of replication and package fission occasionally cause arising packages to miss genes from the ensemble, thus resulting in the death of those packages. A computer simulation, considering the complementarity of RNA as well as abortive termination of replication, yielded results that are similar to those of a preliminary simulation irrespective of these parameters: the results suggest that life could not have started with more than 3 genes, or else the primordial replicase would have to achieve at least a reduction of the replicational error rate by a factor of 13 and a reduction of undue chain termination by a factor of 10 to 25. | 10.1007/BF01808243 |
pubmed_618_19776 | BACKGROUND
The aim of the present study was to explore whether the triglyceride to high density lipoprotein cholesterol ratio [log (TG)/HDL-C] and peripheral blood leukocytes DNA telomere length could predict future islet beta cell function decreased in Chinese type 2 diabetes mellitus (T2DM) during a 6-year cohort.
METHODS
Sixty T2DM patients (without insulin treatment at baseline) were included in the 6-year cohort study. Peripheral blood leukocytes DNA telomere length, HbA1c, blood lipid profile, fatty fat acid, glucose, insulin and C peptide (3 h after a mixed meal) were determined. Delta C peptide area under curve (Delta CP AUC) was used to reflect change in beta cell secretion function (Delta CP AUC = baseline CP AUC - CP AUC after 6 years). Subjects were divided into slow decrease of beta cell function group (Delta CP AUCslow group) and fast decrease group (Delta CP AUCfast group) according to median of Delta CP AUC. Baseline demographic characteristics, clinical variables between two groups were compared. Correlations between baseline data and Delta CP AUC were analyzed.
RESULTS
Baseline log (TG)/HDL-C was positively correlated with Delta CP AUC (r = 0.306, P = 0.027); log (TG)/HDL-C in Delta CP AUCfast group was higher than that in Delta CP AUCslow group (0.103 ± 0.033 vs 0.083 ± 0.030, P = 0.027). There was no significant difference in DNA telomere length between the two groups. Change in DNA telomere length over 6 years was not significantly correlated with baseline blood lipid.
CONCLUSIONS
In Chinese T2DM patients, high baseline log (TG)/HDL-C ratio predicts fast progression of islet beta cell dysfunction. It may be a simple index to predict progression speed of islet beta cell dysfunction. | 10.1111/1753-0407.12229 |
pubmed_407_3630 | OBJECTIVE
To describe the efficacy and safety of IL-1-targeting drugs, anakinra and canakinumab, in patients with mevalonate kinase deficiency (MKD).
METHODS
A questionnaire was sent to French paediatric and adult rheumatologists to retrospectively collect information on disease activity before and after treatment with IL-1 antagonists from genetically confirmed MKD patients. We assessed the frequency of crises and their intensity using a 12-item clinical score built for the purpose of the study.
RESULTS
Eleven patients were included. Anti-IL-1-targeting drugs were used continuously in all but one patient who received anakinra on demand. Daily anakinra (nine patients) or canakinumab injections every 4-8 weeks (six patients, in four cases following anakinra treatment) were associated with complete remission in four cases and partial remission in seven. The median score during MKD attacks decreased from 7/12 before treatment to 3/12 after anakinra and 1/12 after canakinumab. The number of days with fever during attacks decreased from 5 before treatment to 3 after anakinra and 2 after canakinumab. Marked decrease of C-reactive protein and serum amyloid A protein were recorded. Side effects were mild or moderate; they consisted of local pain and inflammation at injection site, infections and hepatic cytolysis.
CONCLUSION
Continuous IL-1 blockade brings substantial benefit to MKD patients. Controlled trials are necessary to further assess the clinical benefit and treatment modalities in these patients. | 10.1093/rheumatology/kes097 |
pubmed_686_5054 | Conditions that necessitate surgery frequently arise in patients with chronic liver disease and cirrhosis. Because cirrhosis has the ability to cause physiologic derangements in every organ system in the body, clinicians face significant challenges in preoperative preparation of the patient with cirrhosis in order to decrease postoperative morbidity and mortality. Emergent operations add an extra dimension of complexity to the clinical picture, due to limited preoperative time to prepare the patient with cirrhosis for surgery. In cases of severely decompensated cirrhosis, clinicians should have in their armamentarium possible alternatives to surgery that can be used to temporize the emergent nature of the disease and improve patient outcomes. The classification of cirrhotic liver disease by Child and Turcotte was initially utilized to predict mortality in patients undergoing surgically placed shunts for portal hypertensive bleeding. Subsequent studies have pointed to the fact that other general and thoracic surgery procedures can be assigned predicted mortality rates according to a similar classification scheme, the modified Child-Pugh score. Patients with cirrhosis facing surgery should undergo a careful history and physical examination and should be accurately placed into a designated Child-Pugh category. Because the modified Child-Pugh class is the most reliable determinant of postoperative morbidity and mortality, every attempt should be made to upgrade a patient's class in a favorable direction prior to surgery. Patients should be carefully evaluated for the presence of ascites and dietary alterations. In addition, medical management with diuretics should be employed to prevent postoperative ascites leak and possible infectious complications including bacterial peritonitis. Perhaps one of the most feared complications in the patient with cirrhosis facing surgery is hemorrhage. Because the liver is vital in maintenance of coagulation homeostasis, several pharmacologic adjuncts may be administered to correct any coagulopathy in the peri-operative period. Several diseases such as cholelithiasis and peptic ulcer disease are known to be more prevalent in the cirrhotic patient, and clinicians treating these diseases should have a thorough understanding of the pathophysiology of cirrhosis and portal hypertension. Patients with cirrhosis and portal hypertensive bleeding that are considered good surgical candidates (ie, Child-Pugh class A) may benefit from surgical portasystemic shunt in contrast to angiographically placed portacaval shunt (ie, transjugular intrahepatic portosystemic shunt ) due to the lack of durable patency and cost effectiveness in the latter. In patients with cirrhosis awaiting orthotopic liver transplantation, TIPS may be a lifesaving temporizing technique that is utilized as a bridge to transplantation. | 10.1007/s11938-005-0034-8 |
pubmed_523_53 | Of 140 patients with malignant tertian malaria seen during 1956 to 1967 10 died. Death was caused by cerebral malaria in all cases. Since 1968 more intensified treatment has resulted in the complete recovery of three patients and the partial recovery of one, all of whom had been in a cerebral malaria coma for various periods of time before admission and in whom a fatal outcome was expected. In these cases a polypragmatic therapeutic approach using intravenous low molecular weight dextran, besides the usual quinine and fluids, corticosteroids, heparin and urea, separately or combined, was adopted. | 10.1136/bmj.1.5751.714 |
pubmed_957_19993 | The aim of the present study was to examine the hypothesis that, compared to typically reading children matched on regular word reading, adults with basic literacy (either adult literacy students or adult basic education students) struggle on phonologically demanding tasks but are relatively performant on orthographic demanding tasks, and hence present a performance pattern similar to that of dyslexic children. Using various reading and phoneme awareness tests, we therefore compared the adults to both typically reading children from Grades 3 and 4 and dyslexic children, these two groups being matched to the adults on regular word reading. The dyslexic children were also compared to either chronological age- or reading level-matched children. The hypothesis was only partly supported by the data, as results depended on the subgroup of adults considered. While the literacy students presented poorer phoneme awareness and a somewhat stronger length effect in reading than the dyslexic children, the basic education students outperformed the latter on irregular word reading. The adults, and in particular the literacy students, also relied frequently on orthography in a complex phoneme awareness task. Taken together, these results suggest that adults with basic literacy rely more on visual memory than both dyslexic and typically reading children. This opens the question of whether the peculiar profile of these adults is intrinsic to adult literacy acquisition or is related to the way they are taught and trained to read and write. The results also highlight the need for better characterization of subgroups of adults with basic literacy. | 10.1007/s11145-022-10347-6 |
pubmed_1092_25181 | BACKGROUND
Clinically isolated syndromes affecting the brainstem may present with rare manifestations such as neurogenic pulmonary oedema (NPO).
OBJECTIVES
We present the case of a 23 year-old man with NPO caused by Tako-Tsubo cardiomyopathy (TTC) as a first manifestation of multiple sclerosis (MS).
METHODS AND RESULTS
A brain magnetic resonance imaging scan at admission showed multiple supra and infratentorial white matter inflammatory demyelinating lesions. This examination was repeated 2 and 4 weeks after symptoms onset and active lesions showing contrast uptake were identified, two of them involving the pons and the medulla oblongata, probably affecting the solitary tract nucleus. Cerebrospinal fluid oligoclonal bands were detected. The patient was treated with a 3-day course of 1g intravenous methylprednisolone presenting a significant and progressive improvement. The proposed underlying physiopathology is an excessive secretion of catecholamines resulting in myocardial stunning and ventricular failure. Two months later he developed optic neuritis and disease-modifying treatment was initiated.
CONCLUSIONS
Clinicians should consider a possible neurological origin of TTC, and according to the clinical characteristics of the patient, MS may be suspected. | 10.1177/1352458516638557 |
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