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pubmed_374_18939
BACKGROUND The aim of the study was to assess the effect of circRNA CDYL on myocardial angiogenesis after acute myocardial infarction (AMI). MATERIAL AND METHODS We compared changes in circRNA CDYL and myocardial angiogenesis in myocardial infarction tissue and normal heart tissue by establishing a myocardial infarction mouse model to clarify the relationship between circRNA CDYL and changes in myocardial infarction and myocardial angiogenesis. Secondly, we used the RegRNA website to predict downstream miRNA, and we performed gain-of-function and loss-of-function experiments. RESULTS CircCDYL was downregulated in myocardial tissues and hypoxia myocardial cells, and overexpression and downregulation of circCDYL improved and aggravated, respectively, heart function after AMI. CircCDYL overexpression and downregulation can promote and inhibit, respectively, proliferation of cardiomyocytes in vitro. Finally, we found that circCDYL can sponge miR-4793-5p and regulate its expression, and then miR-4793-5p regulates APP expression. CONCLUSIONS CircCDYL can promote the proliferation of cardiomyocytes through the miR-4793-5p/APP pathway.
10.12659/MSM.923188
pubmed_322_22655
Cognitive dysfunction can adversely impact the walking ability of people with multiple sclerosis. However, valid and reliable standardized clinical tools to measure cognitive-motor interference or dual-tasking in people with multiple sclerosis remain lacking. This study evaluated the validity and reliability of the modified Walking and Remembering Test (mWART) in people with multiple sclerosis. Eleven adults (mean ± SD age, 51.1 ± 13.4 years) with multiple sclerosis (Expanded Disability Status Score, 2.0-6.0) and six adults (mean ± SD age, 41.5 ± 17.2 years) without multiple sclerosis were administered the mWART twice over a 2-week period. Participants were tested on gait and digit span length under single-task and dual-task conditions according to the mWART procedures over a 10-m walkway. intraclass correlation coefficient2,k were 0.961 for single-task gait velocity (P < 0.001), 0.968 for dual-task gait velocity (P < 0.001), 0.829 for single-task digit span (P = 0.004), and 0.439 for dual-task digit span (P = 0.154). Single-task gait velocity (P = 0.001) and dual-task gait velocity (P = 0.002) were able to discriminate between groups but dual-task costs were similar between participants with and without multiple sclerosis. Those with severe disability demonstrated the greater dual-task cost of gait velocity (P = 0.030). This study provides preliminary evidence of the mWART's validity and reliability in measuring dual-task performance in patients with multiple sclerosis with mild to severe disability. More research is required in more heterogeneous samples of persons with multiple sclerosis.
10.1097/MRR.0000000000000493
pubmed_159_8971
In the present study, we investigated the removal of an emerging pesticide lindane from aqueous solution using synthesized aluminum hydroxide Al(OH)3 (bayerite) nanomaterials with surface modification by an anionic surfactant sodium dodecyl sulfate (SDS). The Al(OH)3 nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) and zeta potential. The lindane removal using SDS-modified nano-aluminum hydroxide nanoparticles (SMNAH) achieved removal of up to 93.68%, which was 3.3 times higher than that of nano-aluminum hydroxide nanoparticles. The adsorptive removal conditions were studied and found to have an adsorption time of 60 min, a pH of 6, an adsorbent dosage of 25 mg/mL and an ionic strength of 10 mM NaCl. After reusing four times, the removal efficiency of lindane using SMNAH still reached 75%. Two-step adsorption can fit adsorption isotherms of lindane onto SMNAH at two salt concentrations. On the basis of the change in zeta potential, surface functional groups and adsorption isotherms, we suggest that the formation of a bilayer micelle induced the removal of lindane.
10.3390/polym12040960
pubmed_550_4310
A new class of predictive model developed in a liquid system is extended in order to quantify gelatin gel matrix structure effects on the growth of Listeria innocua and Lactococcus lactis (both in mono- and coculture, and both producing mainly lactic acid). It was observed that gelatin does not only act as a structuring agent but also alters the buffering capacity of the medium. Model extension occurs in two stages, describing chemical and microbiological processes, respectively. Firstly, equations relating undissociated lactic acid concentration and total lactic acid concentration on the one hand, and undissociated lactic acid concentration and pH on the other hand, are extended to account for the effects of gelatin concentration. Secondly, these equations are incorporated into the growth model to describe the combined effect of gelatin concentration, (undissociated) lactic acid and pH on the growth of either microorganism. The description of the model is in good agreement with the experimental data acquired in monoculture conditions. In a subsequent model validation step, when gelatin concentration and total lactic acid profile of the coculture experiments are used as inputs, the developed growth model consisting of condensed knowledge extracted from the monoculture experiments, is able to predict accurately the interaction effect occurring in coculture. The study suggests that, on the one hand, the extent of the effects of undissociated lactic acid and pH on microbial growth in structured food systems can be modified by the increase in buffering capacity, which can protect microorganisms and eventually promote higher levels of cell growth in comparison with liquid culture conditions. On the other hand, food matrix structure, in casu the gelatin, reduces the rate of microbial multiplication. Both effects are incorporated in the growth model developed in this research.
10.1016/j.ijfoodmicro.2007.04.015
pubmed_178_10162
The effect of physical training on fatty acid synthesis in vivo was studied. After the rats had free access to a running wheel for 50 days, the rate of fatty acid synthesis estimated using 3H2O in adipose tissues of trained rats was about three times higher than that of sedentary rats in both the light and dark period. The rate of fatty acid synthesis in the liver but not in the brown adipose tissue was also slightly enhanced by physical training. The number of adipocytes was not affected, but the size of adipocytes was reduced by physical training. In trained rats, the rate of fatty acid synthesis in adipocytes whose diameter was similar to that of sedentary rats was about 10 times higher than that of sedentary rats. Within adipose tissue, the rate of fatty acid synthesis correlated positively to the diameter of adipocytes both in the sedentary and trained rats. These findings mean that the adaptive increase in fatty acid synthesis seen in adipocytes of trained rats is not secondary to the reduction in size of adipocytes.
10.1152/ajpendo.1983.245.1.E8
pubmed_615_13093
OBJECTIVE To get scientific basis for further health education through the research of the road construction workers' KBP before and after the interventions of highway AIDS prevention project. METHODS Multi-stage random sampling method was employeed to select workers of 8 sites from 14 sites along highway to investigate their AIDS knowledge, belief and performance (KBP) before and after highway AIDS prevention project. RESULTS Over 90% of the investigated workers had ever heard about AIDS, and the non-skilled workers of lower educational level improved more after intervention. The correct answer rate of the three transmitting ways of AIDS of drivers which is the focused group of highway before and after intervention had the obvious statistical significance (P<0.05), and the other group's correct answer rates also had improved after intervention. Most people's understanding of preventing AIDS through correct use of condoms when having sex had a statistically significant difference(P<0.05) after prevention. The rates of using condoms of foremen and skilled workers when having sex with commercial sex worker/casual partner increased after intervention. CONCLUSIONS The health education of HIV among the road construction workers is effective and further health education of HIV prevention should be carried out among the road construction workers to improve their knowledge and awareness of avoiding the high-risk behaviors.
pubmed_615_13093
pubmed_804_9317
Precise genome editing in human induced pluripotent stem cells (iPSCs) significantly enhances our capability to use human iPSCs for disease modeling, drug testing and screening as well as investigation of human cell biology. In this study, we seek to achieve conditional expression of the CD55 gene in order to interrogate its functions. We used two human iPSC lines that have unique genotypes, and constructed an inducible Cas9 gene expression system that is integrated at the AAVS1 safe harbor site in the human genome. Using paired guide RNAs, we observed efficient knock-out with an intended deletion in the coding region of several genes including CD55 and ETV6 genes. This paired guide RNA approach enabled us to efficiently identify homozygous iPSC clones with an intended deletion. Once an iPSC clone lacking CD55 expression was identified and characterized, we were able to use the same doxycycline system to induce expression of a CD55 transgene from a piggyBac vector, in both undifferentiated and differentiated iPSCs. This single cell line of gene knock-out complemented with an inducible transgene is sufficient to achieve conditional expression of the CD55 gene. The methodology described here is broadly applicable to other genes in order to interrogate their functions.
10.1016/j.scr.2018.03.003
pubmed_113_614
In this study, interactions of Fe3O4 magnetic nanoparticles with serum albumin biomolecules in aqueous solutions were considered. The studies were conducted with the laser correlation spectroscopy and optical analysis of dehydrated films. It was shown that the addition of magnetite to an albumin solution at low concentrations of up to 10-6 g/L led to the formation of aggregates with sizes of up to 300 nm in the liquid phase and an increase in the number of spiral structures in the dehydrated films, which indicated an increase in their stability. With a further increase in the magnetite concentration in the solution (from 10-4 g/L), the magnetic particles stuck together and to albumin, thus forming aggregates with sizes larger than 1000 nm. At the same time, the formation of morphological structures in molecular films was disturbed, and a characteristic decrease in their stability occurred. Most stable films were formed at low concentrations of magnetic nanoparticles (less than 10-4 g/L) when small albumin-magnetic nanoparticle aggregates were formed. These results are important for characterizing the interaction processes of biomolecules with magnetic nanoparticles and can be useful for predicting the stability of biomolecular films with the inclusion of magnetite particles.
10.3390/ijms221910734
pubmed_100_22659
There is great demand for the development of novel therapies for ischemic cardiovascular disease, a leading cause of morbidity and mortality worldwide. We report here on the development of a completely synthetic cell-free therapy based on peptide amphiphile nanostructures designed to mimic the activity of VEGF, one of the most potent angiogenic signaling proteins. Following self-assembly of peptide amphiphiles, nanoscale filaments form that display on their surfaces a VEGF-mimetic peptide at high density. The VEGF-mimetic filaments were found to induce phosphorylation of VEGF receptors and promote proangiogenic behavior in endothelial cells, indicated by an enhancement in proliferation, survival, and migration in vitro. In a chicken embryo assay, these nanostructures elicited an angiogenic response in the host vasculature. When evaluated in a mouse hind-limb ischemia model, the nanofibers increased tissue perfusion, functional recovery, limb salvage, and treadmill endurance compared to controls, which included the VEGF-mimetic peptide alone. Immunohistological evidence also demonstrated an increase in the density of microcirculation in the ischemic hind limb, suggesting the mechanism of efficacy of this promising potential therapy is linked to the enhanced microcirculatory angiogenesis that results from treatment with these polyvalent VEGF-mimetic nanofibers.
10.1073/pnas.1016546108
pubmed_122_11543
In this work, we have developed a reducible, self-assembling disulfide cross-linked and peptide-based micelle system for codelivery of miR-4638-5p and DTX to improve the efficacy of castration-resistant prostate cancer (CRPC) therapy. The result showed that DTX in micelles (DTX-VPs) inhibited cell growth and induced apoptosis more effectively than free DTX both in vitro and in vivo. In addition, the DTX and miR-4638-5p loaded micelles (Co-VPs) achieved the most pronounced anticancer effect of all groups. Immunohistochemical analysis indicated that miR-4638-5p in micelle system could effectively downregulate the expression of Kidins220 and further improve the anticancer effect by enhancing tumor cell apoptosis and suppressing tumor cell proliferation. Finally, the bioimaging analysis demonstrated that DIR in micelles (DIR-VPs) showed a higher concentration and a longer retention time in tumor tissue than did free DIR, which indicated an excellent tumor-targeting ability of the micelle system. All these results suggest that codelivery of miR-4638-5p and DTX via polypeptide micelle system has a potential for CRPC treatment.
10.1021/acs.molpharmaceut.8b01074
pubmed_282_23189
Cerebral malaria induced by Plasmodium berghei ANKA infection is dependent on the sequestration of cytotoxic T cells within the brain and augmentation of the inflammatory response. Herein, we demonstrate that inhibition of protein tyrosine phosphatase (PTP) activity significantly attenuates T cell sequestration within the brain and prevents the development of neuropathology. Mechanistically, the initial upregulation of CXCR3 on splenic T cells upon T cell receptor stimulation was critically decreased through the reduction of T cell-intrinsic PTP activity. Furthermore, PTP inhibition markedly increased IL-10 production by splenic CD4+ T cells by enhancing the frequency of LAG3+CD49b+ type 1 regulatory cells. Overall, these findings demonstrate that modulation of PTP activity could possibly be utilized in the treatment of cerebral malaria and other CXCR3-mediated diseases.
10.1038/s41598-017-05609-1
pubmed_929_8416
Recently, technologies such as face detection, facial landmark localisation and face recognition and verification have matured enough to provide effective and efficient solutions for imagery captured under arbitrary conditions (referred to as "in-the-wild"). This is partially attributed to the fact that comprehensive "in-the-wild" benchmarks have been developed for face detection, landmark localisation and recognition/verification. A very important technology that has not been thoroughly evaluated yet is deformable face tracking "in-the-wild". Until now, the performance has mainly been assessed qualitatively by visually assessing the result of a deformable face tracking technology on short videos. In this paper, we perform the first, to the best of our knowledge, thorough evaluation of state-of-the-art deformable face tracking pipelines using the recently introduced 300 VW benchmark. We evaluate many different architectures focusing mainly on the task of on-line deformable face tracking. In particular, we compare the following general strategies: (a) generic face detection plus generic facial landmark localisation, (b) generic model free tracking plus generic facial landmark localisation, as well as (c) hybrid approaches using state-of-the-art face detection, model free tracking and facial landmark localisation technologies. Our evaluation reveals future avenues for further research on the topic.
10.1007/s11263-017-0999-5
pubmed_63_23166
The role of Constant Observation (COb) in the general hospital is addressed. The difficulties of managing acute psychological disturbance in the general hospital are described. Concerns about confused behavior and suicidal risk appear to be the most common reasons for ordering COb. Organic brain syndrome is the most common diagnosis made in patients receiving COb. Medico-legal, ethical and therapeutic aspects of COb are noted. To our knowledge there is no research evidence that COb significantly decreases the rate of suicide in the general hospital. It appears that the role of COb is enshrined in the general hospital as a result of medico-legal process in addition to its therapeutic role. Further research in this area is needed.
pubmed_63_23166
pubmed_613_10030
In the Spring of 2009, a veterinarian reported suspected classical swine fever (CSF) on a multiplier pig farm in the southern part of The Netherlands (close to the Belgian border). Over a 5-week period there had been a number of sick sows and an excessively high percentage of stillborn and preterm piglets. Sick animals were treated with anti-inflammatory drugs and antibiotics, but did not respond as well as anticipated. A visiting specialist team from the Food Safety Authority could not exclude CSF as the cause of the clinical problems and sent blood samples to the reference laboratory in Lelystad for a PCR test on CSF antigen. Fortunately, test results obtained 6 hours later were negative for CSF, and the disease control measures were lifted. It later appeared that porcine reproductive and respiratory syndrome (PRRSV) might have been responsible for the problems. But what if CSF had caused the clinical problems? A CSF-transmission model was used to simulate CSF outbreaks dependent on the duration of the high-risk period (HRP). As the duration of the HRP increased, there was an exponential growth in the number of pig farms infected during this period. Simulations also showed that with a longer HRP, the virus spread over greater distances from the source herd. It was also investigated whether a possible CSF outbreak could be detected on the basis of an increased mortality and hence increased number of cadavers sent to a rendering plant. However, the calculated mortality incidence was not sensitive enough to serve as an alarm signal. It is recommended that CSF-exclusion diagnostics be used much earlier in similar clinical situations on pig farms.
pubmed_613_10030
pubmed_223_5302
Perovskite solar cells (PSCs) have the potential to become one of the most cost-efficient photovoltaic devices. However, current fabrication methods of PSCs still require strict environment control and ultrahigh purity chemicals, which could prevent their large-scale commercialization. To tackle this challenge, the role of water is the first to be thoroughly understood in a perovskite formation process. Until now, there is still controversy about whether water is harmful or beneficial for perovskite formation, not to mention exactly what role water plays therein. In this Focus article, we review recent studies on water involved chemical reactions, solvent interaction, intermediates, and crystal growth in the perovskite film formation process, in order to bring out a full picture about what water does in the perovskite formation process. As our current understanding stands, a suitable amount of water could be of help for growing high quality perovskite films due to the resultant formation of intermediates, such as MAPbI3·H2O, which facilitates the conversion from precursors to perovskites. However, too much water would induce the formation of relatively stable components, such as (MA)4PbI6·2H2O, which are left in the product-films as impurities resulting in degraded device performance. Continual efforts should be made to further understand and develop water-involved strategies for consistent PSC fabrication under ambient conditions.
10.1039/d0nh00270d
pubmed_419_2159
This work had the objectives to (1) evaluate the susceptibility of various Rhipicephalus microplus populations to commercial acaricides, and (2) select commercial acaricides (50-80% effective) and evaluate the effects of binary combinations of the phenylpropanoid (E)-cinnamaldehyde with selected commercial acaricides to control R. microplus under laboratory and field conditions. Using adult immersion tests with 116 populations and 14 commercial acaricides, products showing 50-80% effectiveness (percent control) with the lowest number of active ingredients were selected. Acaricides containing amitraz or chlorfenvinphos were tested in combination with (E)-cinnamaldehyde on a field population (strain CM). We found that (E)-cinnamaldehyde enhanced the activity of both commercial acaricides against R. microplus larvae; however, the enhancement was more accentuated when using amitraz. Experiments combining (E)-cinnamaldehyde + amitraz on unfed larvae and engorged females from another population (strain Gyn) were performed, verifying (E)-cinnamaldehyde enhanced the activity of amitraz. In the field experiment, the application of (E)-cinnamaldehyde appeared toxic to the tick hosts (cattle). We concluded that (E)-cinnamaldehyde enhanced the activity of amitraz against unfed larvae and engorged females of R. microplus; however, in the field test this phenylpropanoid caused intoxication in the cattle. Studies searching for new combinations of compounds from essential oils with amitraz deserve attention, as well as studies to develop formulations using amitraz + (E)-cinnamaldehyde that will be efficient and will not have toxic effects in cattle.
10.1007/s10493-022-00743-6
pubmed_183_16019
A method for exactly representing a point source starting field in a Fourier parabolic equation calculation is presented. The formulation is based on an exact, analytic expression for the field in vertical wave number space (k space). The field in vertical coordinate space (z space) is obtained via a Fourier transform of the k-space field. Thus, one can directly control the Fourier components of the starting field, so that nonpropagating components are excluded. The relation of the exact starting field to the standard Gaussian starting field is demonstrated analytically. Examples of the numerical implementation of the exact starting field are given.
10.1121/1.2719044
pubmed_1088_9562
BACKGROUND Antigen-based (as opposed to whole organism) vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity. METHODOLOGY/PRINCIPAL FINDINGS Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes) can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets. CONCLUSIONS/SIGNIFICANCE By combining our novel strategy with existing methods of epitope prediction based on physical properties of an individual protein, we believe that this method offers a robust method for characterizing the breadth of epitope-specificity within a specific polyserum. This strategy is useful as a tool for monitoring immunity following vaccination and can also be used to define relevant epitopes for the creation of novel vaccines.
10.1371/journal.pone.0005309
pubmed_689_15217
Hermansky-Pudlak syndrome (HPS) is a heterogeneous disorder combining oculocutaneous albinism (OCA) and a platelet function disorder of varying severity as its most prominent features. The genes associated with HPS encode for different BLOC- (biogenesis of lysosome-related organelles complex) complexes and for the AP-3 (adaptor protein-3) complex, respectively. These proteins are involved in maturation, trafficking, and the function of lysosome-related organelles (LROs) such as melanosomes and platelet δ-granules. Some patients with different types of HPS can develop additional complications and symptoms like pulmonary fibrosis, granulomatous colitis, and immunodeficiency. A new type of HPS has recently been identified associated with genetic alterations in the BLOC1S5 gene, which encodes the subunit Muted of the BLOC-1 complex. Our aim was to unravel the genetic defect in two siblings with a suspected HPS diagnosis (because of OCA and bleeding symptoms) using next generation sequencing (NGS). Platelet functional analysis revealed reduced platelet aggregation after stimulation with ADP and a severe secretion defect in platelet δ-granules. NGS identified a novel homozygous essential splice site variant in the BLOC1S5 gene present in both affected siblings who are descendants of a consanguine marriage. The patients exhibited no additional symptoms. Our study confirms that pathogenic variants of BLOC1S5 cause the recently described HPS type 11.
10.3390/cells10102630
pubmed_192_19122
Tetramethyl thiuram disulfide (thiram) is a dithiocarbamate, which is widely used on seeds and storing food grains. The incorporation of thiram into the food chain could be a risk for both human beings and animals. Thiram-contaminated feed has been considered a common cause of tibial dyschondrolplasia (TD) in many avian species. The molecular mechanism of action of thiram on TD involving microRNA (miRNA) is not fully understood. For this purpose, the morbidity and pathologic changes were evaluated to understand the TD, and high-throughput RNA sequencing (RNA-Seq) was performed to explore the differentially expressed miRNAs (DEGs). RT-qPCR was used to confirm the validity as compared with sequencing data. The results showed that the marked alterations in the growth plate of the TD chickens were noticeable, with shrinking cells and irregular chondrocyte columns as compared with control group. In this study, we identified total 375 (p < 0.1), 340 (p < 0.05) and 266 (p < 0.01) significant DEGs between the TD and control groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs showed that the target miRNAs were significantly enriched in different treatment groups, such as apoptosis, mRNA surveillance pathway, mitophagy-animal, etc. This study provides theoretical basis for in-depth understanding the pathogenesis of thiram-induced TD and explore the new insights towards the proposed molecular mechanism of specific miRNA as biomarkers for effective gene diagnosis and treatment of TD in broilers.
10.1016/j.ecoenv.2019.03.043
pubmed_186_24666
BACKGROUND Black sparrowhawks (Accipiter melanoleucus) recently colonised the Cape Peninsula, South Africa, where the species faces competition for their nest sites from Egyptian geese (Alopochen aegyptiaca) which frequently usurp black sparrowhawk nests. In this paper, we test the hypothesis that multiple nest building by black sparrowhawks is a strategy to cope with this competitor, based on a 14-year long term data set. RESULTS Two main results support the hypothesis: first, the numbers of intact nests per breeding season in black sparrowhawk territories increased as levels of geese interactions increased, specifically when usurpation occurred. Usurpation occurred significantly more often at nests later in the season, and may provide a further explanation for the advancement of the black sparrowhawk breeding season towards earlier breeding attempts which results in an overall extension of the breeding period (over 9 months) that has been found in our study population. Second, nest usurpation had a negative impact on black sparrowhawks' reproductive performance at the 'nest' level, but not at the 'territory' level when multiple nests were available within the same breeding season, suggesting that this strategy was effective for dealing with this competitor. However, our results do not rule out long term negative consequences of these interactions, for example, reduced adult survival rates or reduced lifetime reproductive success, due to the higher energy demand required to build several nests each breeding season. CONCLUSIONS Our results suggest that black sparrowhawks avoid direct conflict with this large and aggressive competitor and instead choose the passive strategy in allocating more resources to multiple nest building. Our research further highlights the importance of behavioural plasticity, which might be especially important for city-dwelling species in the face of global urbanisation.
10.1186/s12862-016-0671-7
pubmed_570_23870
BACKGROUND The present study describes a computerized registry of cardiovascular disease patients in a large health maintenance organization in Israel. The registry is aimed to be used by health professionals to identify cardiovascular disease patients and to follow the courses of their illnesses and risk factors. METHODS In 1998, the registry was initiated using advanced information technology that integrated personal computerized community and hospital records, data from laboratory tests, dispensed medications, physiological signals, radiological images, and reports from investigations and procedures. RESULTS Between 1998 and 2007, the number of patients with cardiovascular diseases that were identified by the registry has increased from 34,144 to 80,339. During this period, the age-adjusted prevalence rates have risen from 3.7% to 5.1% and from 1.9% to 2.6%, among men and women, respectively. The percentage of ischemic heart disease patients who reached target LDL was doubled, from 21% in 2000 to 50% in 2006. The average stay in hospital declined from 11.7 to 8.6 days. Primary myocardial infarction rates declined 33% and 54% in men aged 54-65 and women aged 65-74 years, respectively. CONCLUSIONS The present study provides, for the first time in Israel, data on selected quality of care and clinical outcomes using a large, population-based registry of cardiovascular disease patients. It demonstrates a significant improvement in the adherence with LDL tests and achieving target LDL levels and a subsequent decline in incidence of myocardial infarction within ten years since its establishment.
10.1016/j.ijcard.2010.08.002
pubmed_635_3535
BACKGROUND Many individuals with Ehlers-Danlos Syndrome (EDS) are hypermobile, suffer from long term pain, and have complex health problems. Since these sometimes have no objective physical signs, individuals with EDS sometimes are referred for psychiatric evaluation. The aim was therefore to identify the level of anxiety and quality of life in a Swedish group of individuals with EDS. METHODS A postal survey in 2008 was distributed to 365 members over 18 years of the Swedish National EDS Association and 250 with EDS diagnosis responded. Two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and SF-36, were used. A Swedish population study was used to compare results from SF-36. Independent Student's t-test was used to compare differences between groups, possible relationships were tested using Spearman's correlation coefficient and the General Linear Model was used for regression analyses. Higher scores on HADS represent higher levels of anxiety and depression and higher scores on SF-36 represent higher quality of health. RESULTS Of the respondents 74.8% scored high on anxiety and 22.4% scored high on depression on the HADS. Age, tiredness and back pain was independently associated with the HAD anxiety score in a multiple regression analysis, When comparing the SF-36 scores from the EDS group and a Swedish population group, the EDS group scored significantly lower, indicating lower health-related quality of health than the general population (p < 0.001). CONCLUSIONS In comparison with a Swedish population group, a lower health-related quality of life was found in the EDS group. Also, higher levels of anxiety and depression were detected in individuals with EDS. The importance to explore the factors behind these results and what initiatives can be taken to alleviate the situation for this group is emphasized.
10.1186/s12891-015-0549-7
pubmed_56_11724
The brain possesses a remarkable capacity to compensate for changes in inputs resulting from a range of sensory impairments. Developmental studies of sound localization have shown that adaptation to asymmetric hearing loss can be achieved either by reinterpreting altered spatial cues or by relying more on those cues that remain intact. Adaptation to monaural deprivation in adulthood is also possible, but appears to lack such flexibility. Here we show, however, that appropriate behavioral training enables monaurally-deprived adult humans to exploit both of these adaptive processes. Moreover, cortical recordings in ferrets reared with asymmetric hearing loss suggest that these forms of plasticity have distinct neural substrates. An ability to adapt to asymmetric hearing loss using multiple adaptive processes is therefore shared by different species and may persist throughout the lifespan. This highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.
pubmed_56_11724
pubmed_392_5888
People usually use the method of job analysis to understand the requirements of each job in terms of personnel characteristics, at the same time use the method of psychological measurement to understand the psychological characteristics of each person, and then put the personnel in the appropriate position by matching them with each other. With the development of the information age, massive and complex data are produced. How to accurately extract the effective data needed by the industry from the big data is a very arduous task. In reality, personnel data are influenced by many factors, and the time series formed by it is more accidental and random and often has multilevel and multiscale characteristics. How to use a certain algorithm or data processing technology to effectively dig out the rules contained in the personnel information data and explore the personnel placement scheme has become an important issue. In this paper, a multilayer variable neural network model for complex big data feature learning is established to optimize the staffing scheme. At the same time, the learning model is extended from vector space to tensor space. The parameters of neural network are inversed by high-order backpropagation algorithm facing tensor space. Compared with the traditional multilayer neural network calculation model based on tensor space, the multimodal neural network calculation model can learn the characteristics of complex data quickly and accurately and has obvious advantages.
10.1155/2021/3250062
pubmed_419_15397
The purpose of this study was to determine the effect of walking training "Interval Walking Training (IWT)" on oral health status. Participants were divided into two groups: an exercise intervention group and a non-intervention group (control). The intervention group consisted of 59 subjects (20 males, 39 females) aged 50 years or older who participated in the IWT program in Matsumoto from 2019 to April 2022. The control group consisted of 33 subjects (14 males and 19 females) aged 50 years or older who have visited Niigata University Medical and Dental Hospital and agreed to participate in the study. The intervention group underwent walking training (interval walking training) for at least 5-6 months. The walking training consisted of five sets of fast walking above 70% peak aerobic capacity for walking (VO2peak) for 3 min, followed by 3 min of slow walking at ~40% VO2 peak per day for more than four days/week. The oral health status was evaluated for the number of teeth, occlusal force, salivary occult blood, masticatory performance, and tongue pressure. A total of 57 participants were analyzed in the intervention group (18 males and 39 females, age: 66.7 ± 0.8 (mean ± S.E.) years) and 33 participants in the control group (14 males and 19 females, age: 74.5 ± 1.1 (mean ± S.E.) years). There were no significant differences in gender, salivary occult blood, tongue pressure, masticatory performance, or occlusal force between the two groups at the start of the intervention (p = 0.36, p = 0.48, p = 0.42, p = 0.58, and p = 0.08, respectively by unpaired t-test or χ2 test). On the other hand, there were significant differences in age and BMI, with a trend toward lower age and higher BMI in the intervention group (p &lt; 0.001 and p &lt; 0.001, respectively, by unpaired t-test). In terms of rate of change, the intervention group showed a significant increase in occlusal force (F = 4.5, p = 0.04, ANCOVA) and a significant decrease in BMI (F = 7.3, p = 0.009, ANCOVA). No significant differences were observed in the other measured items. It was found that walking training in both middle-aged and older people does not only affect the physical aspect of weight loss but may help maintain and improve the occlusal force.
10.3390/ijerph192114465
pubmed_940_4724
BACKGROUND Shared neurobiological characteristics of patients with schizophrenia and their siblings may represent "intermediate phenotypes" that may more closely reflect the genetic susceptibility underlying this illness. We sought evidence of such phenotypes using magnetic resonance spectroscopy based on previously described regional abnormalities in levels of the neuronal marker N-acetyl-aspartate (NAA) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophrenia. METHODS We studied 47 schizophrenics, 60 unaffected siblings, and 66 healthy control subjects with long echo time multislice proton magnetic resonance spectroscopic imaging, primarily measuring NAA, creatine plus phosphocreatine (CRE), and choline-containing compounds. RESULTS Both patients and their unaffected siblings had significant reductions in hippocampal area NAA/CRE as compared with control subjects. As exploratory analyses, estimates of heritability were performed. Although quantitative correlation of hippocampal NAA between patients and sibs was low (likely reflecting measurement noise), qualitatively defined "low hippocampal NAA/CRE phenotypes" yielded relative risk estimates (lambda s) of between 3.8 and 8.8, suggesting this characteristic is heritable. CONCLUSIONS Our finding adds to the evidence that hippocampal abnormalities are associated with schizophrenia and may represent a novel biological phenotype for genetic studies of schizophrenia.
10.1016/s0006-3223(98)00264-9
pubmed_449_5216
Conventional two-dimensional echocardiography has become a well established tool for evaluation of cardiovascular diseases. Recent introduction of two-dimensional transesophageal echocardiography has widened the ultrasonic examination possibilities for the heart and the great vessels. This paper describes 6 standard transesophageal transducer positions which have proven to be representative and of diagnostic value. In order to facilitate structure identification and interpretation of the anatomic relation transesophageal recordings were compared with corresponding anatomic sections.
10.1055/s-2007-1013072
pubmed_970_18322
Untargeted metabolomics aims to quantify the complete set of metabolites within a biological system, most commonly by liquid chromatography/mass spectrometry (LC/MS). Since nearly the inception of the field, compound identification has been widely recognized as the rate-limiting step of the experimental workflow. In spite of exponential increases in the size of metabolomic databases, which now contain experimental MS/MS spectra for over a half a million reference compounds, chemical structures still cannot be confidently assigned to many signals in a typical LC/MS dataset. The purpose of this Perspective is to consider why identification rates continue to be low in untargeted metabolomics. One rationalization is that many naturally occurring metabolites detected by LC/MS are true "novel" compounds that have yet to be incorporated into metabolomic databases. An alternative possibility, however, is that research data do not provide database matches because of informatic artifacts, chemical contaminants, and signal redundancies. Increasing evidence suggests that, for at least some sample types, many unidentifiable signals in untargeted metabolomics result from the latter rather than new compounds originating from the specimen being measured. The implications of these observations on chemical discovery in untargeted metabolomics are discussed.
10.1021/jacs.9b13198
pubmed_918_8964
Quality of family planning counseling is likely associated with whether or not women continue to use the same contraceptive method over time. The Method Information Index (MII) is a widely available measure of contraceptive counseling quality but little is known about its association with rates of method continuation. The index ranges from 0 to 3 based on a client's answer to whether she was told about other methods, potential side effects with her chosen method, and what to do if she experienced side effects. Using data from a prospective cohort study of 1,998 social franchise clients in Pakistan and Uganda, we investigated the relationship between reported baseline MII and the risk of method continuation over 12 months using survival analysis and Cox proportional hazard models. At baseline, about 65% of women in Pakistan and 73% of women in Uganda reported receiving information about all 3 MII aspects. In Pakistan, 59.4% of the 165 women who stopped using their modern method did so while still in need of contraception. In Uganda, of the 77 women who stopped modern method use, 64.9% discontinued while in need. Despite important differences in the demographics and method mix between the 2 countries, we found similar associations between baseline MII and discontinuation: in both countries as the MII score increased, the risk of discontinuation while in need decreased. In Pakistan, the risk of contraceptive discontinuation was 64% lower (crude hazard ratio [HRcrude]=0.36; P=.03), and 72% lower (HRcrude=0.28; P=.007), among women who were told about any 2, or any 3 aspects of MII, respectively. After adjusting for additional covariates, only the difference in the risk of contraceptive discontinuation between MII=3 and MII=0 remained statistically significant (HRadj=0.35; P=0.04). In Uganda, women who reported being informed about all aspects of MII were 80% less likely to discontinue while in need (HRadj=0.20; P<.001), women informed about any 2 aspects of MII were 90% less likely (HRadj=0.10; P<.001), and women who were informed about any 1 aspect of MII were 68% less likely (HRadj=0.32; P<.02) to discontinue contraceptive use while in need as compared to women who reported not being informed about any aspect of MII. Baseline MII scores were positively associated with method continuation rates in our sample of clients from social franchises in both Pakistan and Uganda and could potentially be used as an indicator of contraceptive counseling quality.
10.9745/GHSP-D-18-00407
pubmed_687_974
The present study examined SMAD family member 4 (Smad4), SMAD family member 2 (Smad2) and phosphorylated (p-)Smad2 expression in biopsy specimens from patients with invasive breast ductal carcinoma, in order to assess their abilities as prognostic markers. A total of 126 tissue samples were selected, and the expression of Smad2, p-Smad2 and Smad4 in carcinoma tissues was detected by immunostaining, and the association between protein expression and clinicopathological variables was analyzed. Smad4 expression was negatively correlated with human epidermal growth factor receptor 2 in carcinoma tissues, and Smad4 expression was consistent with that of p-Smad2. Although multivariate analysis revealed that Smad2, p-Smad2 and Smad4 were not independent predictors, Kaplan-Meier curves demonstrated that Smad4 positivity was correlated with a longer overall survival (OS) and progression-free survival (PFS) time. However, upon analysis of combined markers, there was a significant difference between the p-Smad2/Smad4 co-positive and co-negative patients; the latter tended to exhibit a shorter OS and PFS time, and multivariate analysis revealed that the combined expression of p-Smad2 and Smad4 may be used as an independent prognostic factor. These results suggested that the assessment of p-Smad2 and Smad4 protein expression in breast ductal carcinoma biopsy specimens may provide additional prognostic information.
10.3892/ol.2020.11297
pubmed_421_7050
The green synthesis of NPs through plant extracts can be a modest, one-pot alternative synthesis to the conventional physical or chemical method. The prime focus of this study is to produce MNPs by the reducing effect of Bauhinia tomentosa leaf extract, and it was immobilized in porcine pancreatic lipase (PPL). Synthesized NPs were characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Raman spectroscopy, UV-Vis Spectrometry, Thermogravimetry, and Differential Scanning Calorimeter (DSC), Zeta potential test, VSM, BET and Fourier Transform Infrared Spectroscopy (FTIR). The effect of process parameters was studied, about the efficiency of immobilization are enzyme stability, the extent of enzyme reusability, its separation from products, the activity of immobilized enzyme, recovery, and its loss. Finally, the immobilized lipase was used for the synthesis of 1,3-diolein using enzyme-mediated esterification of oleic acid and glycerol. Under optimized condition (reaction temp-55 [Formula: see text]C; molar ratio-2.5:1; pH-7) diolein yield was achieved to be 94%. Therefore, this work was further used for the industrial production of 1,3-diacylglycerol since a perfect enzyme-catalyzed process was observed.
10.1038/s41598-021-87960-y
pubmed_949_6267
PsaA and PsaB are homologous integral membrane proteins that form the heterodimeric core of photosystem I. Domain-specific antibodies were generated to examine the topography of PsaA and PsaB. The purified photosystem I complexes from the wild type strain of Synechocystis sp. PCC 6803 were treated with eight proteases to study the accessibility of cleavage sites in PsaA and PsaB. Proteolytic fragments were identified using the information from N-terminal amino acid sequencing, reactivity to antibodies, apparent mass, and specificity of proteases. The extramembrane loops of PsaA and PsaB differed in their accessibility to proteases, which indicated the folded structure of the loops or their shielding by the small subunits of photosystem I. NaI-treated and mutant photosystem I complexes were used to identify the extramembrane loops that were exposed in the absence of specific small subunits. The absence of PsaD exposed additional proteolytic sites in PsaB, whereas the absence of PsaE exposed sites in PsaA. These studies distinguish PsaA and PsaB in the structural model for photosystem I that has been proposed on the basis of x-ray diffraction studies (Krauss, N., Schubert, W.-D., Klukas, O., Fromme, P., Witt, H. T., and Saenger, W. (1996) Nat. Struct. Biol. 3, 965-973). Using osmotically shocked cells for protease treatments, the N terminus of PsaA was determined to be on the n side of the photosynthetic membranes. Based on these data and available published information, we propose a topological model for PsaA and PsaB.
10.1074/jbc.272.35.21793
pubmed_373_6973
Lifelong dietary compliance prevents the long-term effects associated with celiac disease. However, this simple solution, diet, has many long-reaching effects on the children affected with celiac disease and their families. Assisting families in coping with this chronic illness is necessary for children and families to develop a sense of control. An overview of celiac disease is presented through the use of a case study. Guidelines are given to enable the healthcare provider to understand and help families through the process of adapting to a child with a chronic illness. Recommendations for nutritional management with helpful suggestions related to making celiac disease an everyday part of family life are discussed.
10.1097/00001610-199705000-00003
pubmed_464_7812
More than 12 months have passed since the World Health Organization (WHO) declared Coronavirus Disease 19 (COVID-19), caused by the SARS-CoV2 virus, to be a pandemic on 11 March 2020. The entire world scientific community agrees that at this time vaccine is the most promising weapon to combat the infection and the severity of the disease. According to the document "Draft landscape of COVID-19 candidate vaccines" by WHO, 272 vaccines against SARS-CoV-2 virus are in development, although only four of these, produced by Pfizer-BioNTech (Pfizer, Inc. and BioNTech), Moderna, AstraZeneca, and Janssen companies, respectively, have been approved by European Medicines Agency and Italian Medicines Agency and subsequently distributed nationwide for use. These vaccines are the result of highly innovative procedures and are quite different from each other in terms of composition. Even clinicians in various medical fields may be unfamiliar with the effects of these vaccines. There is the strong emerging need for dermatologists to understand the crucial role of vaccines, with a focus on the need to vaccinate patients suffering from immune-mediated skin diseases, such as psoriasis, while taking the ongoing treatment into consideration regarding the timing of vaccination. Similarly, psoriasis patients aware of having an immune-mediated and inflammatory disease are increasingly asking the dermatologist information about the efficacy and safety of vaccines against SARS-CoV-2 virus. In this narrative review of the literature and critical analysis of the recommendations of the Italian Ministry of Health, we analyze the implications of the vaccination campaign on dermatological patients with psoriasis undergoing immunosuppressive treatment.
10.1007/s13555-021-00610-z
pubmed_1105_12907
The first systematic investigation of an annelid genome has revealed that the genes of the marine worm Platynereis dumerilii are more closely related to those of vertebrates than to those of insects or nematodes. For hundreds of millions of years vertebrates have preserved exon-intron structures descended from their last common ancestor with the annelids.
10.1186/gb-2006-7-1-203
pubmed_187_6190
A collection of C-terminal deletion mutants of the influenza A virus NS1 gene has been used to define the regions of the NS1 protein involved in its functionality. Immunofluorescence analyses showed that the NS1 protein sequences downstream from position 81 are not required for nuclear transport. The capacity of these mutants to bind RNA was studied by in vitro binding tests using a model vRNA probe. These experiments showed that the N-terminal 81 amino acids of NS1 protein are sufficient for RNA binding activity. The collection of mutants also served to map the NS1 sequences required for nuclear retention of mRNA and for stimulation of viral mRNA translation, using the NP gene as reporter. The results obtained indicated that the N-terminal 113 amino acids of NS1 protein are sufficient for nuclear retention of mRNA and stimulation of viral mRNA translation. The possibility that this region of the protein may be sufficient for virus viability is discussed in relation to the sequences of NS1 genes of field isolates and to the phenotype of known viral mutants affected in the NS1 gene.
10.1093/nar/25.21.4271
pubmed_1080_7574
Progressive brainstem and cerebellar signs developed in a previously healthy 70-year-old man over a course of seven days. A pontine mass characterized by CT and MRI suggested an infiltrating primary pontine glioma. Gross postmortem examination showed a medullary-pontine hemorrhage. Microscopic analysis disclosed an undifferentiated large cell carcinoma which was found to originate from the lung. Differential diagnoses in cases of suspected brainstem lesions are given, including metastatic tumors which are rare when presenting as a solitary brainstem mass. Optimal patient management should be formulated on the basis of histopathological diagnosis rather than imprecise imaging data. Exact tissue diagnosis will also avoid an extensive and expensive search for an occult systemic cancer. The roles of radiation, chemotherapy and surgery are also discussed.
pubmed_1080_7574
pubmed_614_19439
Silver nanoparticles (AgNPs) are widely used as an antibiotic agent in textiles, wound dressings, medical devices, and appliances such as refrigerators and washing machines. The increasing use of AgNPs has raised concerns about their potential risks to human health. Therefore, this study was aimed to determine the impact of AgNPs in germ cell specific complications in mice. The administration of AgNPs results in toxicity in mice; however, a more detailed understanding of the effects of AgNPs on germ cells remains poorly understood. Here, we demonstrate the effects of AgNPs (20 nm in diameter) in a mouse Sertoli and granulosa cells in vitro, and in male and female mice in vivo. Soluble silver ion (Ag(+))-treated cells were used as a positive control. We found that excessive AgNP-treated cells exhibited cytotoxicity, the formation of autophagosomes and autolysosomes in Sertoli cells. Furthermore, an increase in mitochondrial-mediated apoptosis by cytochrome c release from mitochondria due to translocation of Bax to mitochondria was observed. In in vivo studies, the expression of pro-inflammatory cytokines, including tumor necrosis factor α, interferon-γ, -6, -1β, and monocyte chemoattractant protein-1 were significantly increased (p < 0.05). Histopathological analysis of AgNP-treated mice shows that a significant loss of male and female germ cells. Taken together, these data suggest that AgNPs with an average size of 20 nm have negative impact on the reproduction.
10.3109/17435390.2015.1073396
pubmed_1097_1906
Complete understanding of the folding process that connects a structurally disordered state of a protein to an ordered, biochemically functional state requires detailed characterization of intermediate structural states with high resolution and site specificity. While the intrinsically inhomogeneous and dynamic nature of unfolded and partially folded states limits the efficacy of traditional X-ray diffraction and solution NMR in structural studies, solid state NMR methods applied to frozen solutions can circumvent the complications due to molecular motions and conformational exchange encountered in unfolded and partially folded states. Moreover, solid state NMR methods can provide both qualitative and quantitative structural information at the site-specific level, even in the presence of structural inhomogeneity. This article reviews relevant solid state NMR methods and their initial applications to protein folding studies. Using either chemical denaturation to prepare unfolded states at equilibrium or a rapid freezing apparatus to trap non-equilibrium, transient structural states on a sub-millisecond time scale, recent results demonstrate that solid state NMR can contribute essential information about folding processes that is not available from more familiar biophysical methods.
10.1016/j.bpc.2010.05.009
pubmed_466_15740
By means of a complex of anatomical, histological and histochemical methods cardiac vessels have been studied in 20 control dogs and in 84 dogs with experimentally produced circulatory disturbances peculiar for congenital heart diseases presented as an open arterial duct, coarctation of the aorta and the pulmonary trunk stenosis. The experimental animals have been observed for 6-12 months. In the animals with experimentally produced disturbances of the general and coronary hemodynamics hyperplasy in the coronary branches of the arteries appears, it is more pronounced in functionally loaded cardiac parts, as well as thickening of their walls at the expense of new formations and hyperthrophy of smooth muscle cells. In both control and experimental dogs in the coronary vessels at various branching levels certain formations are revealed; they are of compensatory-adaptive value: intimal and adventitial musculature, polypoid pulvinars, muscular-elastic constrictors, muscular cuffs and precapillary sphincters. They differ in structure, sources of their origin and in their functional value. Degree of their manifestation increases significantly after reproduction of the hemodynamic disturbances in the heart vascular system. The active role of these formations in regulation of the coronary circulation is demonstrated owing to a high content of ribonucleinic acid and glycogene in their smooth muscle cells and also an elevated succinate dehydrogenase, cytochromoxydase, acid and alcaline phosphatase activities.
pubmed_466_15740
pubmed_612_7139
Evidence shows that an increased width and thickness of the keratinized mucosa favours peri-implant health. The aim of this network meta-analysis was to compare the clinical effects of alternative biomaterials for peri-implant soft tissue phenotype modification (PSPM) in patients with dental implants when compared to autologous tissue grafts. An electronic search without language or date limitations was performed in four databases and the grey literature for articles published until November 2020. The eligibility criteria included randomized clinical trials (RCTs) evaluating the clinical outcomes of biomaterials for PSPM. A pairwise and network meta-analysis was conducted for each parameter to assess and compare the outcomes between the different treatment arms for the primary and secondary outcomes. A total of 11 RCTs were included in this review. The free gingival graft (FGG) showed the best clinical effect for increasing keratinized mucosa width (KMW). When compared in a network, the FGG demonstrated the best treatment ranking of probability results, followed by connective tissue graft (CTG), acellular dermal matrix (ADM), and xenogeneic collagen matrix (XCM). For the parameters 'mucosa thickness' and 'participant satisfaction with aesthetics', the results were CTG > ADM > XCM and XCM > ADM > CTG, respectively. Autogenous tissue grafts (FGG/CTG) demonstrate the best results in increasing KMW and mucosa thickness when compared to the other biomaterials.
10.1016/j.ijom.2021.07.005
pubmed_904_4454
Inflammatory bowel disease (IBD) is a known medical burden in most developed countries and a significant cause of morbidity. The IBD label includes Crohn's disease (CD) and ulcerative colitis (UC). Pharmacological and surgical intervention are the two main management approaches for IBD. Some drugs have been developed for IBD therapy, but accessibility is limited due to high costs. Furthermore, these agents have demonstrated inactivity over long-term treatment courses. Therefore, an urgent need is present for new treatment options that are safe, able to sustain clinical remission, and improve mucosal gut healing. Seaweed has received much attention in the pharmacological field owing to its various biomedical properties, including the prolongation of blood clotting time, as well as antitumor, anti-inflammation, and antioxidant effects. This study therefore aimed to examine the effects of a dietary polysaccharide-rich extract obtained from Eucheuma cottonii (EC) on a model of colitis. Colitis was induced in male BALB/c mice by the administration of 2.5% (w/v) dextran sulfate sodium (DSS) for 7 days. DSS-induced mice were treated with either one of three different doses of EC extracts (0.35, 0.70, and 1.75 g/kg body weight) or curcumin as a positive control (0.10 g/kg). Mice were sacrificed post-treatment and blood samples were collected. The disease activity index (DAI) and inflammatory cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10) were measured. After treatment for 7 days, EC extract administration protected against weight loss and decreased the colon weight per length ratio. EC extract administration also decreased pro-inflammatory cytokine expression, increased IL-10 levels, and reduced colonic damage. Therefore, a dietary polysaccharide-rich extract from E. cottonii reduced DSS-induced bowel inflammation, thereby becoming a promising candidate for the treatment of colitis.
10.1371/journal.pone.0205252
pubmed_583_5968
Angiotensin II is able to trigger inflammatory responses through an angiotensin II type 1 (AT1) receptor. The role of AT1 receptor in acute lung injury (ALI) is poorly understood. Mice were randomly divided into three groups (n=40 each groups): NS group; LPS group (2mg/kg LPS intratracheally); and LPS+ZD 7155 group, 10mg/kg ZD 7155 (an AT1 receptor antagonist) intraperitoneally 30 min prior to LPS exposure. Samples from the lung were isolated and assayed for histopathology analyses or proinflammatory gene expressions, angiotensin II receptors expressions and nuclear factors activities. LPS exposure resulted in severe ALI, elevated levels of TNF-alpha and IL-1 beta mRNA expressions, and increased activities of NF-kappaB and activated protein (AP)-1. Upregulation of AT1 receptor and down-regulation of AT2 receptor were also observed after LPS challenge. Pretreatment with ZD 7155 significantly inhibited the increase of AT1 receptor expression and upregulated AT2 receptor expression. ZD 7155 also reduced the mRNA expression of TNF-alpha and IL-1 beta, inhibited the activation of NF-kappaB and AP-1, and improved lung histopathology. These findings suggest that antagonism of AT1 receptor inhibits the activation of NF-kappaB and AP-1 in the lung, which may mediate the release of TNF-alpha and IL-1 beta and contribute to LPS-induced ALI.
10.1016/j.cyto.2009.08.001
pubmed_95_9010
Oligosaccharides, involved in regulation of plant developmental and defensive processes, were tested to determine their ability to enhance proliferation of human keratinocytes. A mixture of alginate oligosaccharides remarkably stimulated keratinocyte growth and [3H]thymidine uptake in the presence of epidermal growth factor (EGF). The activity was comparable to bovine pituitary extract, a common complement in keratinocyte culture, and additive on BPE-induced stimulation. The most effective oligosaccharide in the mixture was identified and its chemical structure was determined. These findings demonstrate a novel activity of alginate oligosaccharide(s) in keratinocyte growth and suggest a possible co-factor for EGF-dependent stimulation in medium for keratinocytes.
10.1016/s0014-5793(97)00386-4
pubmed_434_19806
This study aims to experimentally determine the strain rate effects on the compressive stress-strain behavior of bovine liver tissues. Fresh liver tissues were used to make specimens for mechanical loading. Experiments at quasi-static strain rates were conducted at 0.01 and 0.1 s(-1). Intermediate-rate experiments were performed at 1, 10, and 100 s(-1). High strain rate (1000, 2000, and 3000 s(-1)) experiments were conducted using a Kolsky bar modified for soft material characterization. A hollow transmission bar with semi-conductor strain gages was used to sense the weak forces from the soft specimens. Quartz-crystal force transducers were used to monitor valid testing conditions on the tissue specimens. The experiment results show that the compressive stress-strain response of the liver tissue is non-linear and highly rate-sensitive, especially when the strain rate is in the Kolsky bar range. The tissue stiffens significantly with increasing strain rate. The responses from liver tissues along and perpendicular to the liver surface were consistent, indicating isotropic behavior.
10.1016/j.jmbbm.2010.09.007
pubmed_192_8100
We propose a pump-dump control scheme using sub-10 fs pulses to enhance the photochemical formation of the three-membered C-S-O ring oxathiirane from the parent H2CSO sulfine molecule. The ultrashort nature of the pulses is essential to promptly alter the photoinduced dynamics, e.g., while a bond is elongating, which is key to selectively form the oxathiirane by radiative dumping. We carried out an in silico pump-dump experiment with excited-state dynamics simulations that include the interaction with electric field of the pump and dump pulses. By applying the dump pulse when the CS bond is elongating, the population transferred to the ground state will form the oxathiirane with a branching ratio of 4, much higher than the one solely due to nonradiative relaxation (0.66). The overall oxathiirane yield can be increased by up to 17% when the 6 fs IR dump pulse is applied at a delay time of 47 fs.
10.1063/1.5089124
pubmed_490_17835
We introduce a simple delay-scanned complete spatiotemporal intensity-and-phase measurement technique based on wavelength-multiplexed holography to characterize long, complex pulses in space and time. We demonstrate it using pulses emerging from multi-mode fiber. This technique extends the temporal range and spectral resolution of the single-frame STRIPED FISH technique without using an otherwise-required expensive ultranarrow-bandpass filter. With this technique, we measured the complete intensity and phase of up to ten fiber modes from a multi-mode fiber (normalized frequency V ≈10) over a ~3ps time range. Spatiotemporal complexities such as intermodal delay, modal dispersion, and material dispersion were also intuitively displayed by the retrieved results. Agreement between the reconstructed color movies and the monitored time-averaged spatial profiles confirms the validity to this delay-scanned STRIPED FISH method.
10.1364/OE.25.024015
pubmed_994_24006
Currently, the most popular form of testosterone replacement is the topical gels that require daily applications and incur a risk of transfer of testosterone to partners and family. One of the problems with testosterone replacement is the short half-life of testosterone. A long-acting formulation is appealing to patients and physicians. In 1972, fused crystalline testosterone pellets were approved in the USA by the FDA but they were not marketed until 2008. Pharmacokinetics studies were available on a different formulation from which much can be learned and applied to the current formulation, Testopel®. The decay kinetics, pituitary suppression, and effect on other sex steroids are reviewed as well as the short-term complication rates. This review should provide the testosterone pellet implanter a better understanding of the physiology of testosterone pellet supplementation for hypogonadism.
10.1007/s11930-014-0033-7
pubmed_972_11705
Lignin quantification in apple pomace residues was carried out using a microwave oven to replace traditional refluxing during the mild acidolysis step to augment the selectivity of this step towards cleavage of lignin-carbohydrate bonds and to reduce the time needed to quantify lignin. The pressure, temperature and time were optimized by response surface methodology and the results were compared to the Klason lignin methodology. Temperature and pressure had a significant positive effect (p < 0.05) on the determination of lignin. However, the time was also significant (p < 0.05) on lignin quantification. The optimal conditions of digestion were: 30 bar, 170 °C for 15 min. The digestion using microwave (lignin content = 33 % w/w) was more accurate (p < 0.05) than the the traditional refluxing (lignin content = 27 % w/w).
10.1007/s10529-012-0991-7
pubmed_32_18172
Megakaryocyte growth and development factor (MGDF) is a novel cytokine that binds to the c-mpl receptor and stimulates megakaryocyte development in vitro and in vivo. This report describes the ability of recombinant human (r-Hu) MGDF to affect megakaryocytopoiesis in normal nonhuman primates. r-HuMGDF was administered subcutaneously to normal, male rhesus monkeys once per day for 10 consecutive days at dosages of 2.5, 25, or 250 micrograms/kg of body weight. Bone marrow and peripheral blood were assayed for clonogenic activity and peripheral blood counts were monitored. Circulating platelet counts increased significantly (P < .05) for all doses within 6 days of r-HuMGDF administration and reached maximal levels between day 12 and day 14 postcytokine administration. The 2.5, 25.0, and 250.0 micrograms/kg/d doses elicited peak mean platelet counts that were 592%, 670%, and 449% of baseline, respectively. Bone marrow-derived clonogenic data showed significant increases in the concentration of megakaryocyte (MEG)-colony-forming unit (CFU) and granulocyte-erythroid-macrophage-megakaryocyte (GEMM)-CFU, whereas that of granulocyte-macrophage (GM)-CFU and burst-forming unit-erythroid (BFU-e) remained unchanged during the administration of r-HuMGDF. These data show that r-HuMGDF is a potent stimulator of thrombocytopoiesis in the normal nonhuman primate.
pubmed_32_18172
pubmed_1077_9358
A novel photo-induced homogeneous atom transfer radical polymerization (ATRP) system is constructed using an organic copper salt (Cu(SC(S)N(C2 H5 )2 )2 ) as a photo-induced catalyst at 30 °C. Herein, N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA) is used as a ligand, ethyl 2-bromophenylacetate (EBPA) as an ATRP initiator, and (2,4,6-trimethylbenzoyl) diphenylphosphine oxide (TPO) as a photo-induced radical initiator to establish an ICAR (initiators for continuous activator regeneration) ATRP using methyl methacrylate (MMA) as a modal monomer. The effect of the concentration of the organic copper on the polymerization is investigated in detail. It is found that well-controlled polymerization can be obtained even with the amount of (Cu(SC(S)N(C2 H5 )2 )2 decreasing to a 1.56 ppm level, with the molecular weight of the resultant polymers increasing linearly with monomer conversion while maintaining a narrow molecular weight distribution (M¯w/M¯n < 1.3).
10.1002/marc.201400393
pubmed_402_17307
UNLABELLED A characteristic pattern seen on captopril renography is described that is due to systemic hypotensive response. Most patients with these findings on captopril renography do not receive renal artery angiograms in our clinic because it is usually recognized. However, this pattern has received little attention in the medical literature and may be misinterpreted as being due to physiologically significant renal artery hypertension. METHODS Over the last 3 y, renal artery angiograms were performed on three patients with systemic hypotensive response pattern on captopril renography. This allowed a unique opportunity to correlate the results of the captopril renogram with the renal artery angiograms in this patient population. Captopril renography was performed with a glomerular filtration agent, diethylenetriamine pentaacetic acid (DTPA), and a tubular agent, o-iodohipurate (OIH). RESULTS Renal artery angiograms showed no evidence of renal artery stenosis in three patients with systemic hypotensive response pattern on captopril renography. Systemic hypotension on captopril renograms results in preserved uptake of both DTPA and OIH and hyperconcentration in the cortex and collecting system. CONCLUSION The systemic hypotensive response pattern seen on captopril renography is a distinctive pattern that does not represent physiologically significant renal artery stenosis.
pubmed_402_17307
pubmed_890_18176
Shrublands are one of the major types of ecosystems in the desert regions of northern China, which is expected to be substantially more sensitive to global environmental changes, such as widespread nitrogen enrichment and precipitation changes, than other ecosystem types. However, the interactive effects of nitrogen and precipitation on them remain poorly understood. We conducted a fully factorial field experiment simulating three levels of precipitation (ambient, +20%, +40%) and with two levels of nitrogen deposition (ambient, 60 kg N ha-1 yr-1) in a desert shrubland in the Mu Us Desert of northern China. We used plant architectural traits (plant cover, volume, twig size and number) as proxies to predict aboveground net primary productivity (ANPP) of the dominant shrub (Artemisia ordosica Krasch), and assessed the responses of plant productivity and architectural traits to water and nitrogen addition. We found significant differences in twig size and number of A. ordosica under water and nitrogen treatments but not in shrub cover/volume, which suggest that twig size and number of the shrub species were more sensitive to environmental changes. The productivity of the overall community was sensitive to increased precipitation and nitrogen, and shrubs played a more important role than herbaceous plants in driving productivity in this ecosystem. Precipitation- and nitrogen-induced increases in vegetation production were positively associated with increases in twig size and number of the dominant shrub. Water addition enhanced the twig length of A. ordosica, while nitrogen addition resulted in increased twig density (the number of twigs per square meter). Water and nitrogen interacted to affect twig length, but not twig number and shrub ANPP. The trade-off, defined as negative covariance between twig size and number, was likely the mechanism underlying the responses of twig length and shrub ANPP to water and nitrogen interactions. Our results highlight the sensitivity of twig size and number as indicators to estimate shrub production and the mechanism underpinning desert shrub ANPP response to global environmental changes.
10.3389/fpls.2016.01908
pubmed_70_8153
MT-SP1 is a type II transmembrane serine protease implicated in a range of human cancers including those of the breast, cervix, ovaries, prostate, colon and gastrointestinal tract. Mouse models have shown it to be critical for proper epidermal development and postnatal survival. However, the role of this enzyme in normal and malignant biology has not yet been fully elucidated. Several groups have identified putative substrates of MT-SP1 in an effort to understand the possible biological processes in which this protease may be involved. Methods for substrate identification include comparing known protein cleavage sequences with MT-SP1 specificity data, in vitro cleavage assays, examining genetic microarrays for enzyme/substrate coexpression, immunohistochemistry for colocalization, and a variety of phenotypic observations using cell culture and mouse models. Given the inherent limitations of each individual method, substrate plausibility is best substantiated using a combination of experimental approaches. Here we review MT-SP1 substrates identified to date and the possible physiological implications of substrate cleavage in cell-microenvironment interactions. This data indicates that MT-SP1 is capable of playing roles in growth factor activation, receptor activation and inactivation, protease activation, and ectodomain shedding. We also present for the first time vascular endothelial growth factor receptor 2 (VEGFR-2) as a putative substrate for MT-SP1.
10.2741/2698
pubmed_219_12330
The amyloid C-terminal fragment (βCTF) of the amyloid precursor protein (APP) is the cleaved component of APP by beta secretase-1 (BACE1), which shows similar neurotoxicity as amyloid beta (Aβ) in many ways. Evidence suggested that in addition to Aβ, βCTF might also participate in the pathogenesis of Alzheimer's disease (AD). In recent years, the relationship between βCTF processing and hyperphosphorylated tau has attracted increasing research attention. In this study, we established an animal model of tau hyperphosphorylation with okadaic acid (OA) treatment, and analyzed βCTF processing in vivo. The βCTF level was found to increase in neurons, which was most likely caused by the induction of OA and BACE1 overexpression. Furthermore, these results provide the first evidence that βCTF can predominately accumulate in the axons of neurons in a hyperphosphorylated tau state in vivo, and suggested that the redistribution of βCTF is involved in the pathogenesis of AD. These results indicate that BACE1 could be a therapeutic target of AD by affecting the processing of βCTF.
10.4238/2014.August.15.4
pubmed_234_21355
The metabolism, toxicity and results of tests for carcinogenicity have been reviewed with respect to the safety for humans of coumarin present in foodstuffs and from fragrance use in cosmetic products. Coumarin is a natural product which exhibits marked species differences in both metabolism and toxicity. The majority of tests for mutagenic and genotoxic potential suggest that coumarin is not a genotoxic agent. The target organs for toxicity and carcinogenicity in the rat and mouse are primarily the liver and lung. Moreover, the dose-response relationships for coumarin-induced toxicity and carcinogenicity are non-linear, with tumour formation only being observed at high doses which are associated with hepatic and pulmonary toxicity. Other species, including the Syrian hamster, are seemingly resistant to coumarin-induced toxicity. There are marked differences in coumarin metabolism between susceptible rodent species and other species including humans. It appears that the 7-hydroxylation pathway of coumarin metabolism, the major pathway in most human subjects but only a minor pathway in the rat and mouse, is a detoxification pathway. In contrast, the major route of coumarin metabolism in the rat and mouse is by a 3,4-epoxidation pathway resulting in the formation of toxic metabolites. The maximum daily human exposure to coumarin from dietary sources for a 60-kg consumer has been estimated to be 0.02 mg/kg/day. From fragrance use in cosmetic products, coumarin exposure has been estimated to be 0.04 mg/kg/day. The total daily human exposure from dietary sources together with fragrance use in cosmetic products is thus 0.06 mg/kg/day. No adverse effects of coumarin have been reported in susceptible species in response to doses which are more than 100 times the maximum human daily intake. The mechanism of coumarin-induced tumour formation in rodents is associated with metabolism-mediated, toxicity and it is concluded that exposure to coumarin from food and/or cosmetic products poses no health risk to humans.
10.1016/s0278-6915(99)00010-1
pubmed_1125_12150
Chemotherapy is an essential modality in the treatment of retinoblastoma (RB). Mammalian serine/arginine-rich protein-specific kinase 1 (SRPK1) is a cisplatin-sensitivity-related protein and its downregulation is known to be associated with decreased response to cisplatin and carboplatin. We investigated the expression of SRPK1 in 63 archival RB and correlated its expression with pathologic staging and exposure to chemotherapy. The majority of the RB (62/63) were advanced stage (Groups D and E) with intermediate to high risk of treatment failure according to the new international classification for intraocular RB and SRPK1 was reduced in 32/62 (51%) tumors. SRPK1 protein expression was reduced in (100%) 8/8 RB that had recurred in the orbit or had metastasized. SRPK1 protein expression is reduced in RB with advanced stage of presentation and this may add to drug resistance mechanisms in RB.
10.1002/pbc.21088
pubmed_1133_16948
BACKGROUND The prevalence of rotator cuff repair continues to rise, with a noted transition from open to arthroscopic techniques in recent years. One reported advantage of arthroscopic repair is a lower infection rate. However, to date, the infection rates of these 2 techniques have not been directly compared with large samples at a single institution with fully integrated medical records. PURPOSE To retrospectively compare postoperative infection rates between arthroscopic and open rotator cuff repair. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS From January 2003 until May 2011, a total of 1556 patients underwent rotator cuff repair at a single institution. These patients were divided into an arthroscopic repair group and an open group. A Pearson chi-square test and Fisher exact test were used, with a subgroup analysis to segment the open repair group into mini-open and open procedures. The odds ratio and 95% CI of developing a postoperative infection was calculated for the 2 groups. A multiple-regressions model was then utilized to identify predictors of the presence of infection. Infection was defined as only those treated with surgical intervention, thus excluding superficial infections treated with antibiotics alone. RESULTS A total of 903 patients had an arthroscopic repair, while 653 had open repairs (600 mini-open, 53 open). There were 4 confirmed infections in the arthroscopic group and 16 in the open group (15 mini-open, 1 open), resulting in postoperative infection rates of 0.44% and 2.45%, respectively. Subgroup analysis of the mini-open and open groups demonstrated a postoperative infection rate of 2.50% and 1.89%, respectively. The open group had an odds ratio of 5.645 (95% CI, 1.9-17.0) to develop a postoperative infection compared with the arthroscopic group. CONCLUSION Patients undergoing open rotator cuff repair had a significantly higher rate of postoperative infection compared with those undergoing arthroscopic rotator cuff repair.
10.1177/2325967117715416
pubmed_1133_12978
Cognitive deficits are among the most severe and pervasive consequences of aneurysmal subarachnoid hemorrhage (SAH). A critical step in developing therapies targeting such outcomes is the characterization of experimentally-tractable pre-clinical models that exhibit multi-domain neurobehavioral deficits similar to those afflicting humans. We therefore searched for neurobehavioral abnormalities following endovascular perforation induction of SAH in mice, a heavily-utilized model. We instituted a functional screen to manage variability in injury severity, then assessed acute functional deficits, as well as activity, anxiety-related behavior, learning and memory, socialization, and depressive-like behavior at sub-acute and chronic time points (up to 1 month post-injury). Animals in which SAH was induced exhibited reduced acute functional capacity and reduced general activity to 1 month post-injury. Tests of anxiety-related behavior including central area time in the elevated plus maze and thigmotaxis in the open field test revealed increased anxiety-like behavior at subacute and chronic time-points, respectively. Effect sizes for subacute and chronic neurobehavioral endpoints in other domains, however, were small. In combination with persistent variability, this led to non-significant effects of injury on all remaining neurobehavioral outcomes. These results suggest that, with the exception of anxiety-related behavior, alternate mouse models are required to effectively analyze cognitive outcomes after SAH.
10.1038/s41598-017-07701-y
pubmed_499_20818
Bottlebrush (BB) elastomers, in which load-bearing network strands are densely grafted with side chains, are gaining much attention due to their unique mechanical properties. Herein, we used in situ small-angle X-ray scattering coupled with tensile tests to investigate the microscopic structural changes induced in a model BB elastomer with a controlled network structure under uniaxial deformation. The model BB elastomer was synthesized by end-linking a monodisperse star-shaped BB polymer, which ensured a controlled network structure. The BB elastomer exhibited both significant strain stiffening and backbone chain alignment under uniaxial loading, and these properties were not observed in an analogous side chain-free elastomer and gel. It was also found that the side chains in the BB elastomer did not show any sign of chain orientation even when the attached backbone chain was aligned in the stretching direction. These observations highlighted the roles of side chains: they were structurally disordered at the segment level but their steric repulsion made the backbone chain aligned and overstretched.
10.1039/d2sm00492e
pubmed_695_23993
Rainbow trout with gene editing-induced reductions in serum insulin-like growth factor binding protein (IGFBP)-2b exhibit similar growth performance compared to fish without IGFBP-2b gene disruption. The objective of this study is to determine how the components of the insulin-like growth factor (IGF)/IGFBP system respond to a reduction in serum IGFBP-2b abundance. Editing the IGFBP-2b genes in rainbow trout resulted in an 83% decrease in serum IGFBP-2b in mutants. This resulted in a 35% reduction in serum IGF-I, which was offset by reduced expression of hepatic igfbp-1a2 and increased muscle igfr-1a; these responses suggest that an increased IGF-I signaling capacity offset reductions in serum IGF-I. During feed deprivation, the differential expression of igfbp genes supports the attenuation of the growth inhibitory response, likely due to the further reduction in serum IGF-I that alleviated the need for an IGF-inhibitory response. Unique igfbp expression patterns occurred during refeeding, suggesting an enhanced IGF-I signaling capacity in controls. Collectively, these findings support that the role of IGFBP-2b is to regulate serum IGF-I concentrations. The compensatory regulation of IGF/IGFBP system genes indicates that adjustments in other IGFBP, both circulating and at the local level, maintain IGF-I signaling at a level appropriate for the nutritional state of the fish.
10.3390/genes11121488
pubmed_133_21814
The 16-kDa proteolipid from the hepatopancreas of Nephrops norvegicus belongs to the class of channel proteins that includes the proton-translocation subunit of the vacuolar ATPases. The membranous 16-kDa protein from Nephrops was covalently spin-labeled on the unique cysteine Cys54, with a nitroxyl maleimide, or on the functionally essential glutamate Glu140, with a nitroxyl analogue of dicyclohexylcarbodiimide (DCCD). The intensities of the saturation transfer ESR spectra are a sensitive indicator of spin-spin interactions that were used to probe the intramembranous structure and assembly of the spin-labeled 16-kDa protein. Spin-lattice relaxation enhancements by aqueous Ni(2+) ions revealed that the spin label on Glu140 is located deeper within the membrane (around C9-C10 of the lipid chains) than is that on Cys54 (located around C5-C6). In double labeling experiments, alleviation of saturation by spin-spin interactions with spin-labeled lipids indicates that spin labels both on Cys54 and on Glu140 are at least partially exposed to the lipid chains. The decrease in saturation transfer ESR intensity observed with increasing spin-labeling level is evidence of oligomeric assembly of the 16-kDa monomers and is consistent with a protein hexamer. These results determine the locations and orientations of transmembrane segments 2 and 4 of the 16-kDa putative 4-helix bundle and put constraints on molecular models for the hexameric assembly in the membrane. In particular, the crucial DCCD-binding site that is essential for proton translocation appears to contact lipid.
10.1021/bi991459c
pubmed_738_23061
OBJECTIVES to assess time trend of lifestyles, cardiovascular risk factors, and prevalence of high-risk conditions in random samples of the general adult population residing in Emilia-Romagna, examined in two cross-sectional surveys conducted within the Epidemiological Cardiovascular Observatory (OEC 1998-2002) and the Epidemiological Cardiovascular Observatory/Health Examination Survey (OEC/HES 2008-2012). DESIGN cross-sectional surveys conducted on random samples of general adult population stratified by gender and age group in some municipalities of Emilia-Romagna. SETTINGS AND PARTICIPANTS in Emilia-Romagna, 341 males and 354 females were examined in 1998-2002 and 307 males and 300 females were examined in 2008-2012. MAIN OUTCOME MEASURES cardiovascular risk factors, high risk conditions, and proportion of population following healthy lifestyles recommendations. RESULTS in the second survey, prevalence of hypercholesterolemia and mean values of total and LDL cholesterol were higher. Less than 30% of the sample consumes adequate quantities of vegetables and fish; cheeses, sausages, and sweets are overconsumed, as a higher cholesterol intake. CONCLUSIONS increased in total and LDL cholesterol are partly due to the reach diet, as suggested by nutrient consumption. Appropriate preventive actions for the improvement of the lifestyles and lipid profile in the general population are recommended.
10.19191/EP20.1.P040.016
pubmed_769_1378
The soft and delicate tissue of the brain, which is the center of our coordination, is protected by its surrounding layers. The disruption of these layers results in complicated situations and serious health problems. The brain has three protective layers of bone or skull tissue, the blood tissue layer, and finally the meningeal layer. The layer of blood tissue contains the blood vessels that are located between the skull and the meningeal membranes. If germs or foreign matter enter the fluid through the blood vessels under any circumstances and cause infection, the bones that protect the meninges will break and cause tissue damage. The present study aimed to assess the histological and immunohistochemical characteristics of the brain of rats that underwent induced acute purulent pneumococcal meningitis after antibiotic therapy with Ceftriaxone. A number of 20 white adult male Wistar rats were assigned to three groups. The first group (n=5) regarded as the control were injected with a saline solution into the subarachnoid space in an equivalent amount. The second and third groups of rats (n=5 and 10, respectively) were infected with acute purulent meningitis by the injection of 10 μl of Streptococcus pneumoniae (S. pneumonia) suspension into the subarachnoid space of the brain using a 23-G needle. The various areas of the brains of rats after meningitis induced by S. pneumoniae were examined after the treatment with Ceftriaxone. The S. pneumoniae culture was injected into the subarachnoid space in the area of the rhomboid fossa. Treatment started 18 h after the injection. On day 10, a repeated puncture was performed with the analysis of cerebrospinal fluid in order to confirm the absence of meningitis; thereafter, the animals were taken out of the experiment. No signs of meningitis were found on histological examination. Mild perivascular and pericellular focal edema were revealed with signs of overload of the lymphatic system in the brain and focal ischemic changes in neurons. The investigation of expression with caspase-3 revealed a positive reaction of individual neurons. A positive reaction with antibodies to NeuN and Doublecortin was detected in most neurons; moreover, Glial fibrillary acidic protein (GFAP)-positive astrocytes and their processes were visualized in all layers of the brain substance. The reaction with neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP-2), CD 31, and CD 34 was negative. Typical structure and pictures pointed to an intact brain and purulent meningitis in the first and second groups. The microscopic image and the changes revealed during immunohistochemistry by dual corticosteroid antibodies and neuronal nuclear protein were characterized by predominantly cytoplasmic and perinuclear reactions, respectively. Some neurons are positive for caspase-3 and are related to changes in the characteristic of premature aging.
10.22092/ari.2021.355885.1733
pubmed_228_18966
The β(2) subunit of class Ia ribonucleotide reductase (RNR) contains a diferric tyrosyl radical cofactor (Fe(2)(III)-Tyr(•)) that is essential for nucleotide reduction. The β(2) subunit of Saccharomyces cerevisiae is a heterodimer of Rnr2 (β) and Rnr4 (β'). Although only β is capable of iron binding and Tyr(•) formation, cells lacking β' are either dead or exhibit extremely low Tyr(•) levels and RNR activity depending on genetic backgrounds. Here, we present evidence supporting the model that β' is required for iron loading and Tyr(•) formation in β in vivo via a pathway that is likely dependent on the cytosolic monothiol glutaredoxins Grx3/Grx4 and the Fe-S cluster protein Dre2. rnr4 mutants are defective in iron loading into nascent β and are hypersensitive to iron depletion and the Tyr(•)-reducing agent hydroxyurea. Transient induction of β' in a GalRNR4 strain leads to a concomitant increase in iron loading and Tyr(•) levels in β. Tyr(•) can also be rapidly generated using endogenous iron when permeabilized Δrnr4 spheroplasts are supplemented with recombinant β' and is inhibited by adding an iron chelator prior to, but not after, β' supplementation. The growth defects of rnr4 mutants are enhanced by deficiencies in grx3/grx4 and dre2. Moreover, depletion of Dre2 in GalDRE2 cells leads to a decrease in both Tyr(•) levels and ββ' activity. This result, in combination with previous findings that a low level of Grx3/4 impairs RNR function, strongly suggests that Grx3/4 and Dre2 serve in the assembly of the deferric Tyr(•) cofactor in RNR.
10.1074/jbc.M111.294074
pubmed_267_6518
The permeability of microvasculature in the cerebral cortex, neostriatum, and spinal cord to i.v. injected horseradish peroxidase (HRP) has been investigated in rats following experimental compression to 6.1 bars (abs.) air for 90 min, and subsequent decompression to the ambient pressure in 1 min. For comparison, 1 ml of 2.0 M urea was injected into the right common carotid artery of rats during 15 s. After exposure to compression-decompression, under the light microscope focal leaky areas were found in all the regions examined. The leakage was most prominent in the grey matter of the spinal cord, and the cerebral cortex. In decompressed rats, arterioles were most often the site of peroxidase extravasation, whereas extravasation of HRP was less frequently displayed by capillaries and venules. In urea-treated rats, capillaries and venules frequently displayed extravasation of HRP as well. Parenchymal cells accumulated the trace adjacent to the leaky areas. Under the electron microscope, the extravasation of HRP was associated with peroxidase-containing pleomorphic vesicular structures in the endothelium, both in decompressed and urea-injected rats. Moreover, in contrast to decompressed rats, the junctions between endothelial cells were penetrated by the trace in urea-treated rats. Accordingly, the results indicate that during decompression sickness the pathway for the extravasation of proteins is through vesicular transfer, whereas the injection of hyperosmolar urea induces extravasation, both through vesicular transfer and junctions between the endothelial cells.
10.1007/BF00685387
pubmed_72_15615
The precise regulation of cell-cell communication by numerous signal-transduction pathways is fundamental for many different processes during embryonic development. One important signalling pathway is the evolutionary conserved fibroblast-growth-factor (FGF)-pathway that controls processes like cell migration, axis specification and mesoderm formation in vertebrate and invertebrate animals. In the model insect Drosophila, the FGF ligand / receptor combinations of FGF8 (Pyramus and Thisbe) / Heartless (Htl) and Branchless (Bnl) / Breathless (Btl) are required for the migration of mesodermal cells and for the formation of the tracheal network respectively with both the receptors functioning independently of each other. However, only a single fgf-receptor gene (Tc-fgfr) has been identified in the genome of the beetle Tribolium. We therefore asked whether both the ligands Fgf8 and Bnl could transduce their signal through a common FGF-receptor in Tribolium. Indeed, we found that the function of the single Tc-fgfr gene is essential for mesoderm differentiation as well as for the formation of the tracheal network during early development. Ligand specific RNAi for Tc-fgf8 and Tc-bnl resulted in two distinct non-overlapping phenotypes of impaired mesoderm differentiation and abnormal formation of the tracheal network in Tc-fgf8- and Tc-bnl(RNAi) embryos respectively. We further show that the single Tc-fgfr gene encodes at least two different receptor isoforms that are generated through alternative splicing. We in addition demonstrate through exon-specific RNAi their distinct tissue-specific functions. Finally, we discuss the structure of the fgf-receptor gene from an evolutionary perspective.
pubmed_72_15615
pubmed_198_7390
The adsorption of different types of phosphatidylglycerols onto magnetizable solid particles is studied. The super-paramagnetic magnetite spheres used have an average diameter of only 14 nm and are stabilized by lauric acid to keep them in solution. During incubation and dialysis of this water-based magnetic fluid in the presence of preformed sonicated phospholipid vesicles, magnetoliposomes are formed which are captured from solution with high efficiency by high-gradient magnetophoresis. Support for the bilayer character of the phospholipid coat is derived from both theoretical calculations and experimental data. Phospholipids which form the inner monolayer are adsorbed very quickly with their charged head-group orientated towards the iron oxide surface. The high-affinity character of the binding is reflected in the adsorption isotherms and is further illustrated by their non-extractability with high concentrations of Tween 20. The outer layer assembles through interaction with the exposed hydrocarbon chains. As compared to the inner layer, the phospholipids adsorb at a much slower rate and are displaced by Tween 20 concentrations which usually disrupt conventional membranes. The adsorption isotherms for this layer obey the Langmuir expression. The affinity constants, derived from them, progressively increase as the hydrophobic nature of the phosphatidylglycerols is more pronounced.
10.1007/BF00256482
pubmed_1081_15190
BACKGROUND Patients with irritable bowel syndrome (IBS) frequently present with alterations of autonomic activity, especially higher sympathetic activity. Salivary alpha-amylase (sAA) has been implicated as a non-invasive biomarker to reflect the sympathetic activity. Thus, the current study aimed to determine if alterations of sAA secretion could be addressed in IBS patients. METHODS We recruited twenty-five IBS patients as well as twenty-four age- and sex-matched healthy controls (HCs). Basal and stimulated (by gustatory stimulation with citric acid) saliva samples were collected from each participant, with respective salivary flow rate (SFR) calculated accordingly. Western blotting (WB) was applied to determine the sAA amount by introducing human sAA protein of known quantity. Then the sAA amount ratio was calculated, as expressed by the stimulated sAA amount to basal sAA amount. RESULTS We observed high variability of the basal and stimulated sAA amount in both groups. An apparently higher prevalence of psychiatric disorders was detected in the IBS group, which was consistent with previous studies. Interestingly, we found elevated basal sAA amount in the IBS patients relative to HCs, which implicated higher sympathetic activities in IBS population. Moreover, we observed blunted sAA response to the gustatory stimulation in the IBS patients, which might be of pathophysiological importance for IBS. CONCLUSION This is the first attempt to associate sAA secretion with the pathophysiology of IBS. Our results suggest an autonomic dysfunction in IBS patients.
pubmed_1081_15190
pubmed_43_25131
BACKGROUND Hip fracture is a common osteoporotic fracture with great morbidity and mortality. The utility of ASA classification is limited, as most patients are ≥ASA 3. A reliable predictor of mortality risk could support decision-making. We aimed to evaluate Nottingham hip fracture score (NHFS) for the prediction of 30-day mortality and then to recalibrate the formula converting NHFS to risk of 30-day mortality. METHODS All patients >60 years with surgically treated hip fracture surgery during 2015-16 were assessed. Data was extracted manually from routinely collected clinical data in registry and medical records. Discriminative performance of NHFS and ASA was assessed with C-statistics. The conversion formula from NHFS to risk of 30-day mortality was recalibrated using logistic binominal regression. Observed vs expected ratios of 30-day mortality were compared with the 2012 NHFS-formula and recalibration was performed in a split dataset. RESULTS 1864 patients were included, with 213 deaths within 30 days. C-statistic were 0.64 for NHFS and 0.62 for ASA. Comparing expected values from the 2012-revision with our observed deaths gave a ratio of 1.37. Relating predicted levels of 30-day mortality based on 70% of our cohort vs. 30% test portion of our Swedish dataset gave a ratio of 0.97. DISCUSSION NHFS underestimated mortality in our cohort and showed poor discrimination. Revision of the formula based on a split dataset improved calibration. We suggest NHFS to be routinely implemented to support clinical judgements, expand preoperative assessment and escalate intraoperative monitoring.
10.1111/aas.13966
pubmed_165_16761
This paper presents the design and the evaluation of a method to study prosodic features of discourse structure in unrestricted spontaneous speech. Past work has indicated that one of the major difficulties that discourse prosody analysts have to overcome is finding an independent specification of hierarchical discourse structure as to avoid circularity. Previous studies have tried to solve this problem by constraining the discourse or by basing segmentations on a specific discourse theory. The current investigation first explores the possibility of experimentally determining discourse boundaries in unrestricted speech. In a next stage, it is investigated to what extent boundaries obtained in this way correlate with specific prosodic variables: the features pause, pitch range, and type of boundary tone are studied as a function of discourse structure.
10.1121/1.418114
pubmed_774_10566
OBJECTIVE Anemia is the most common hematological complication of HIV infection that has a significant impact on the quality of life and clinical outcomes. Therefore, the aim of this study was to assess the prevalence and associated factors of anemia among adult HIV positive patients on Anti-retroviral therapy at Deber Tabor hospital, northwest Ethiopia. An institution based cross-sectional study was conducted on 365 HIV/AIDS patients on ART selected using the systematic random sampling technique. Blood samples were analyzed using the Cell-DYN 1800 automated hematology analyzer to measure hemoglobin. Bivariable and multivariable binary logistic regression analyzes were employed to find the predictors at p-value < 0 .2 and 0.05, respectively. RESULTS The overall prevalence of anemia was 34.0%[95% CI (29.0, 39.0)]; taking Zidovudine based antiretroviral regimen (AOR: 5.9, 95% CI 1.04, 13.86), CD4 count < 200 cells/mm3 (AOR: 4.8 95%, CI 1.14, 12.42), inability to read and write (AOR: 3.2, 95% CI (1.24,8.40), inadequate dietary diversity (AOR: 2.2, 95% CI 1.15, 4.26), and female sex (AOR: 1.9, 95% CI 1.06, 3.69) were significantly associated with increased odds of anemia. Therefore, routine screening of hemoglobin level, proper treatment of respondents on zidovudine based ART regimen and increasing productivity to improve dietary diversity are essential to prevent anemia.
10.1186/s13104-019-4214-3
pubmed_720_197
OBJECTIVE The aim of this study was to investigate the correlation between adenosine triphosphate (ATP) 2B1 gene polymorphism in cerebral infarction (CI) patients and the onset of CI. PATIENTS AND METHODS A total of 100 CI patients (CI group) and 88 healthy people who received physical examination (Control group) were enrolled as study subjects. Meanwhile, 4 mL of venous blood was extracted from each subject. The single nucleotide polymorphisms of rs19203, rs13412 and rs28313 in the promoter region of adenosine triphosphate (ATP) 2B1 gene were classified via conformation-difference gel electrophoresis. Chi-square was adopted to test whether the frequency of ATP2B1 genotype distribution conformed to genetic equilibrium law. Meanwhile, the correlations between ATP2B1 alleles and gene polymorphism sites and the onset of CI were analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the level of vascular endothelial growth factor (VEGF) in the serum of CI patients. Furthermore, the correlation of ATP2B1 gene polymorphism with the expression level of VEGF was analyzed. RESULTS Hardy-Weinberg equilibrium analysis revealed that the polymorphisms of three ATP2B1 gene loci were in accordance with genetic equilibrium distribution (p>0.05). According to the results of genetic correlation analysis, the polymorphisms and alleles of ATP2B1 rs19203 and rs13412 were statistically correlated with the onset of CI (p<0.05). However, the rs28313 polymorphism and alleles were not correlated with the onset of CI (p>0.05). In addition, a statistically significant correlation between the polymorphisms of rs19203 and rs13412 and the expression level of VEGF was found in CI patients (p<0.05). CONCLUSIONS Rs19203 and rs13412 in the promoter region of the ATP2B1 gene are correlated with the onset of CI. However, rs28313 bears no relationship with CI.
10.26355/eurrev_201905_17941
pubmed_76_21072
The Authors point out the high frequency of viral infections in a sample of IVDAs. The most significant infections that emerged are CMV and HCV diseases, in contrast with other epidemiological studies.
pubmed_76_21072
pubmed_343_16798
Guilt, a self-conscious emotion, includes self-focused role taking and also correlates with other-oriented role-taking. Excess guilt proneness might be relevant to obsessive compulsive disorders. The white matter (WM) neural correlates of the degree of guilt have not yet been determined. We hypothesized that the WM structures involved in feelings of guilt are associated with social and moral cognition (inferior parietal lobule [IPL], prefrontal cortex [PFC], and cingulate), and aimed to visualize this using diffusion MRI. We investigated the association between regional WM structures (WM volume, and fractional anisotropy, and mean diffusivity [MD]), and feelings of guilt in 1196 healthy, young students using MRI and the Guilty Feeling Scale, which comprises interpersonal situation (IPS; guilt from hurting friends) and rule-breaking situation (RBS; deontological guilt) scores. The primary novel finding presented here is that MD in the right somatosensory and motor cortices from arm to hand were positively correlated with RBS scores. Further, consistent with our hypothesis, RBS scores were positively correlated with MD in the same regions. These results would be predicted by the Macbeth effect, an obsession with dirt leading to hand-washing rituals resulting from guilt, made famous by the Shakespearian character Lady Macbeth. "What, will these hands ne'er be clean?" William Shakespeare (Shakespeare, 1606) Macbeth.
10.1038/s41598-019-48654-8
pubmed_501_13796
Each of nine nursing mothers received one single intramuscular injection of 50 mg pethidine (Dolcontral), between the third and eighth days from childbirth. The highest pethidine concentration, 0.526 mumol/l or 0.13 microgrms/ml, was recorded from breast milk, two hours from application. After 24 hours, the concentration had dropped to 0.081 mumol/l or 0.02 microgram/ml. - The milk-serum quotient was in excess of 1.0. A correlation was found to exist between pethidine concentrations in the serum, on the one hand, and those in mother's milk, on the other. - One single application of Dolcontral is not expected to be of harmful effect on the newborn.
pubmed_501_13796
pubmed_1013_20164
Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Low-dose (i.e., an analgesic dose) morphine is recommended for use in the prehospital (i.e., field) setting. Morphine administration reduces hemorrhagic tolerance in rodents. However, it is unknown whether morphine impairs autonomic cardiovascular regulation and consequently reduces hemorrhagic tolerance in humans. Thus, the purpose of this study was to test the hypothesis that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thirty adults (15 women/15 men; 29 ± 6 yr; 26 ± 4 kg·m-2, means ± SD) completed this randomized, crossover, double-blinded, placebo-controlled trial. One minute after intravenous administration of morphine (5 mg) or placebo (saline), we used a presyncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (mmHg·min), which was compared between trials using a Wilcoxon matched-pairs signed-rank test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat blood pressure (photoplethysmography) during the LBNP test using mixed-effects analyses [time (LBNP stage) × trial]. Median LBNP tolerance was lower during morphine trials (placebo: 692 [473-997] vs. morphine: 385 [251-728] mmHg·min, P < 0.001, CI: -394 to -128). Systolic blood pressure was 8 mmHg lower during moderate central hypovolemia during morphine trials (post hoc P = 0.02; time: P < 0.001, trial: P = 0.13, interaction: P = 0.006). MSNA burst frequency responses were not different between trials (time: P < 0.001, trial: P = 0.80, interaction: P = 0.51). These data demonstrate that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.NEW & NOTEWORTHY In this randomized, crossover, placebo-controlled trial, we found that tolerance to simulated hemorrhage was lower after low-dose morphine administration. Such reductions in hemorrhagic tolerance were observed without differences in MSNA burst frequency responses between morphine and placebo trials. These data, the first to be obtained in conscious humans, demonstrate that low-dose morphine reduces hemorrhagic tolerance. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.
10.1152/ajpheart.00091.2022
pubmed_820_24143
OBJECTIVE Dystrophin is a sarcolemmal membrane protein that prevents the myocyte from oncosis induced by physical stress. Because ischemic preconditioning (IPC) protects mitochondria and prevents oncosis during reperfusion, we hypothesized that dystrophin is an end-target of IPC distal to mitochondrial protection. METHODS AND RESULTS Isolated rat hearts were subjected to 30 min ischemia followed by reperfusion. IPC was introduced by 3 cycles of 5 min ischemia and 5 min reperfusion. The loss of sarcolemmal dystrophin and myocardial ATP during ischemia was comparable between the control and the IPC heart. Similar changes in sarcolemmal dystrophin and myocardial ATP were observed when the heart was treated with 2,4-dinitrophenol (DNP), an uncoupler of mitochondrial respiration, or oligomycin, an inhibitor of mitochondrial F1F0-ATPase. However, the IPC heart increased sarcolemmal dystrophin during reperfusion associated with an increase in tetramethylrhodamine ethylester (TMRE) uptake, an indicator of mitochondrial membrane potential (DeltaPsim), and myocardial ATP and inhibited myocyte oncosis. The increase in myocardial ATP and relocalization of dystrophin to the sarcolemma mediated by IPC was inhibited by treatment with DNP or oligomycin during reperfusion. In vitro experiments demonstrated that mitochondria isolated from the ischemic IPC heart increased ATP generation and facilitated relocalization of dystrophin from the insoluble to the soluble fractions in a manner sensitive to DNP and oligomycin. CONCLUSIONS These results suggest that enhanced relocalization of dystrophin to the sarcolemma during reperfusion may be a mechanistic link between IPC-mediated improvement of mitochondrial function and its protection against oncosis during the early phase of reperfusion.
10.1016/j.cardiores.2006.01.004
pubmed_157_13414
This article provides information about the depositories of parasitic worms in the scientific institutes and museums in the United States, Japan, and Europe (the total number of samples and the availability of types of helminths from various classes), as well as information on the availability of electronic catalogues of the collections in the continental, national, and regional centers for collective use. The extent of this material has determined the necessity of creating digital collections and libraries that would represent a new form of storing, displaying, and exchanging information for scientific research. An analysis was performed of the current state of approaches and methods of development of the specialized information retrieval system (IRS) and databases (DBs) on the parasitic worms in Russia on the basis of a common conceptual data model, taking into account their local use (as desktop systems of database management) and access by scientists worldwide via the Internet.
pubmed_157_13414
pubmed_789_19002
INTRODUCTION Due to the inadequate response to inhaled corticoids, patients with difficult-to-control asthma (DCA) are submitted to oral corticoids or use of Omalizumab. Although it is necessary to treat these patients, a significant relationship between steroid usage and both peripheral and respiratory weakness muscle, results in implications such as loss of quality of life and compromised lung function. Nonetheless, it is not known whether these patients suffer neurophysiological changes due to drug effect. OBJECTIVE To investigate the neurophysiological and functional characteristics of patients with DCA in order to gain a better understanding of the condition. METHOD A cross-sectional study was carried out involving three groups of patients: DCA-C (use of oral corticosteroids), DCA-O (use of omalizumab) and CG (healthy controls matched for age). The assessment involved the six-minute walk test, sit-to-stand test, static balance on a pressure platform, patellar and Achilles reflexes and quadriceps strength in the dominant leg. RESULTS The results revealed no statistically significant differences between the control group and DCA groups in relation to neurophysiological aspects. However, the DCA groups exhibited a significant reduction in functional capacity [decreased muscle strength (p < 0.05), shorter distance covered on walk test (p < 0.05) and lesser number of repetitions on sit-to-stand test (p < 0.05)] in comparison to the control group. CONCLUSION Individuals with DCA exhibited a reduction in functional capacity. The DCA-C group also demonstrated a reduction in muscle strength when compared with control group, likely caused by the continual use of corticoids. However, no neurophysiological alterations were found in the studied population.
10.1016/j.rppneu.2012.02.008
pubmed_1000_16741
The protein subunit of Escherichia coli ribonuclease P (which has a cysteine residue at position 113) and its single cysteine-substituted mutant derivatives (S16C/C113S, K54C/C113S and K66C/C113S) have been modified using a sulfhydryl-specific iron complex of EDTA-2- aminoethyl 2-pyridyl disulfide (EPD-Fe). This reaction converts C5 protein, or its single cysteine-substituted mutant derivatives, into chemical nucleases which are capable of cleaving the cognate RNA ligand, M1 RNA, the catalytic RNA subunit of E. coli RNase P, in the presence of ascorbate and hydrogen peroxide. Cleavages in M1 RNA are expected to occur at positions proximal to the site of contact between the modified residue (in C5 protein) and the ribose units in M1 RNA. When EPD-Fe was used to modify residue Cys16 in C5 protein, hydroxyl radical-mediated cleavages occurred predominantly in the P3 helix of M1 RNA present in the reconstituted holoenzyme. C5 Cys54-EDTA-Fe produced cleavages on the 5' strand of the P4 pseudoknot of M1 RNA, while the cleavages promoted by C5 Cys66-EDTA-Fe were in the loop connecting helices P18 and P2 (J18/2) and the loop (J2/4) preceding the 3' strand of the P4 pseudoknot. However, hydroxyl radical-mediated cleavages in M1 RNA were not evident with Cys113-EDTA-Fe, perhaps indicative of Cys113 being distal from the RNA-protein interface in the RNase P holoenzyme. Our directed hydroxyl radical-mediated footprinting experiments indicate that conserved residues in the RNA and protein subunit of the RNase-P holoenzyme are adjacent to each other and provide structural information essential for understanding the assembly of RNase P.
10.1006/jmbi.1999.3443
pubmed_548_20939
Placebos have been found to affect a number of pathological processes and physiological functions through expectations of clinical improvement. Recently, the study of the placebo effect has moved from the clinical to the physical performance setting, wherein placebos can boost performance by increasing muscle work and by decreasing perceived exertion. However, nothing is known about the neurobiological underpinnings of this phenomenon. Here we show for the first time that a placebo, which subjects believed to be endurance-increasing caffeine, reduces fatigue by acting at the central level on the preparatory phase of movement. In fact, we recorded the readiness potential, which is the expression of the preparatory phase of movement at the level of the supplementary motor area, during repeated flexions of the index finger in a control group that did not receive any treatment and in a placebo group that received placebo caffeine. In the control group, as the number of flexions increased, both fatigue and readiness potential amplitude increased. By contrast, in the placebo group, as the number of flexions increased we found a decrease in perceived exertion along with no increase in readiness potential amplitude. This placebo-induced modulation of the readiness potential suggests that placebos reduce fatigue by acting centrally during the anticipatory phase of movement, thus emphasizing the important role of the central nervous system in the generation of fatigue.
10.1111/ejn.12806
pubmed_897_21219
OBJECT The association of posterior ring apophysis separation (PRAS) with lumbar disc herniation (LDH) is uncommon and represents a true subgroup of disc herniation mainly seen in the adolescent population. The objective of this study was to describe a decade of experience in the care of adult patients with PRAS with LDH, giving particular attention to its diagnosis, surgical treatment, and outcome. METHODS This retrospective study focuses on a case series of adult patients with PRAS associated with LDH who underwent surgery for lumbar disc disease in the author's neurosurgical department between 1999 and 2008. Posterior ring apophysis separation was diagnosed in 87 (5.35%) of 1625 patients surgically treated for LDH; these patients made up the PRAS group. During a 6-month period in 2005, LDH without PRAS was diagnosed in 89 consecutive patients at the same facility; these patients constituted the control group. Presenting symptoms, physical examination findings, and preoperative imaging results were obtained from medical records. Immediate operative results were assessed, as were complications, long-term outcome, and the need for repeat surgery. RESULTS This study is the first to document the distinguishing features between adult patients with and those without PRAS. The difference in average age was statistically significant (p < 0.001) between the study group (36.22 years) and the control group (44.30 years), as was the incidence of male patients (86.20% vs 71.91%, p = 0.020), incidence of military patients (74.71% vs 57.30%, p = 0.015), average duration of symptoms (16.13 vs 8.4 months, p = 0.016), and incidence of reactive scoliosis (19.54% vs 4.49%, p = 0.002). The most common anatomical location of disc herniation in the PRAS group was L5-S1 (51.72%) versus L4-L5 (53.93%) in the control group (p = 0.017). In terms of previous injury, motor deficits, back and/or leg pain, lateral or central location of LDH, mean anteroposterior diameter of disc herniation, hard or soft discs, and surgical complications, there was no statistical difference between the 2 patient groups. Similarly, there was no difference in recurrence rates and clinical outcomes between the patients with or without PRAS. CONCLUSIONS Posterior ring apophysis separation with LDH is probably more common in adults than is generally recognized. It must be suspected when young male patients with persistent sciatic scoliosis and no history of injury show signs of calcified LDH. Computed tomography scanning with sagittal reconstructions is the procedure of choice for diagnosing. The L5-S1 intervertebral disc level is most commonly affected, especially the superior endplate of S-1. This condition needs more extensive surgical exposure and resection to relieve the nerve impingement. The occurrence of an apophyseal lesion was not associated with recurrent disc herniation or a fair outcome.
10.3171/2010.11.SPINE10392
pubmed_270_17110
AIM To investigate the effects of luminal exposure to H2O(2) and two related thiol oxidizing agents on basal and stimulated chloride secretion in native colon using electrophysiological and pharmacological approaches. METHODS Unstripped rat distal colon segments were mounted in Ussing chambers. Potential difference, calculated resistance and short-circuit current across unstripped colon segments were monitored with a dual voltage/current clamp. Paracellular permeability was assessed by measuring the mucosa-to-serosa flux of a fluorescent probe (FITC). RESULTS Luminal exposure to hydrogen peroxide transitorily stimulated chloride secretion without altering barrier function. This stimulatory effect could be blocked by basolateral atropine but not indomethacin. The cysteine and methionine oxidizing compounds, phenylarsine oxide and chloramine T respectively, mimicked the effect of H2O(2), except for a drop in transcolonic resistance after 30 min. In contrast to the observed stimulatory effect on basal secretion, cAMP-stimulated electrogenic ion transport was blunted by luminal H2O(2). However, the Ca(2+)-activated response remained unchanged. CONCLUSION H2O(2) may be an important selective modulator of intestinal ion and water secretion in certain pathologic conditions such as inflammation or ischemia-reperfusion by multiple mechanisms.
10.3748/wjg.v12.i34.5523
pubmed_666_11872
Background: The exact identification of tumor boundaries and related liver segments is especially important for liver tumor surgery. This study aimed to evaluate a new approach for vascular boundary assessment and surgical navigation based on fiber-optic microscopy and microvascular fluorescence labeling. Methods: Antibody clones with fast binding ability were identified and selected using immunofluorescence. We evaluated the endothelial capture efficacy for an anti-mouse CD31 antibody labeled with different fluorophores and different degrees of labeling ex vivo. Segment boundary identification and navigation potential using endothelial capture were explored by two different fiber-optic microscopy systems. Finally, microvasculature labeling and fiber-optic microscopy were used to identify and treat microscopic liver tumors in vivo. Results: The following monoclonal antibodies were selected: anti-mouse CD31 (clone 390), anti-mouse CD54 (YN1/1.7.4), anti-human CD31 (WM59), and anti-human CD54 (HA58). These clones showed fast binding to endothelial cells and had long half-lives. The fluorophore choice and the degree of antibody labeling did not significantly affect capture efficacy in an isolated liver perfusion model. The microvascular system was clearly identified with wide-field fiber-optic microscopy after labeling the endothelium with low doses of specific antibodies, and the specifically labeled liver segment could be microscopically dissected. High antibody doses were required for confocal laser endomicroscopy. After microscopically identifying the vascular margin in vivo, tumor thermoablation strongly reduced tumor size or totally eliminated tumors. Conclusions: We demonstrated that vascular boundaries of liver tumors and locally perfused liver segments were accurately identified and surgical micronavigation was facilitated with fiber-optic microscopy and selected endothelium-specific antibodies.
10.7150/thno.45973
pubmed_203_4951
The in vitro antimicrobial activity of a new series of synthetic fluorine-substituted triaryl alcohols against the human pathogens Staphylococcus aureus, Escherichia coli, and Candida albicans was studied with the aim of overcoming multiple drug resistance and improving the clinical usefulness of antimicrobial drugs. The nature and positions of substituents attached to aromatic rings, as well as their electronegativities and sizes, seem to affect the preferred molecular conformations and, hence, the binding of the compounds to the corresponding cell receptors.
10.1007/s11171-005-0055-z
pubmed_626_17932
Arsenic trioxide, As(2)O(3), has successfully been used to treat acute promyelocytic leukemia (APL). Induction of apoptosis in cancerous cells has been proposed to be the underlying mechanism for the therapeutic efficacy of arsenic. To further understand the cytotoxicity of arsenic compounds in APL cells, HL-60 cells were exposed to graded concentrations of the following arsenicals for up to 48 h: arsenic trioxide (As(III)), sodium arsenate (As(V)), phenylarsine oxide (PAO(III)), monomethylarsonous acid (MMA(III)), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)), and the viability and modes of cell death assessed. The arsenic-exposed cells were stained with annexin V-PE and 7-aminoactinomycin D (7-AAD) and analyzed by flow cytometry in order to detect apoptotic and viable cells while cell morphology was visualized using scanning and transmission electron microscopy. Acridine orange staining and microtubule-associated protein 1 light chain 3 (MAP-LC3) detection were used to recognize autophagic cell death. The results showed that the compounds reduced viable HL-60 cells by inducing apoptosis in a concentration-dependent manner. None of the compounds tested caused a significant change in binding of acridine orange or redistribution of MAP-LC3. Potencies of the six different arsenic compounds tested were ranked as PAO(III)>MMA(III)> or =As(III)>As(V)>MMA(V)>DMA(V). An increase in caspase-3 activity by PAO(III), MMA(III) and DMA(V) implied that these compounds induced apoptosis in HL-60 cells through a caspase-dependent mechanism, but the other arsenic compounds failed to activate caspase-3, suggesting that they induce apoptosis by an alternative pathway.
10.1016/j.taap.2009.05.016
pubmed_10_8240
Coupled oscillators can exhibit complex self-organization behavior such as phase turbulence, spatiotemporal intermittency, and chimera states. The latter corresponds to a coexistence of coherent and incoherent states apparently promoted by nonlocal or global coupling. Here we investigate the existence, stability properties, and bifurcation diagram of chimera-type states in a system with local coupling without different time scales. Based on a model of a chain of nonlinear oscillators coupled to adjacent neighbors, we identify the required attributes to observe these states: local coupling and bistability between a stationary and an oscillatory state close to a homoclinic bifurcation. The local coupling prevents the incoherent state from invading the coherent one, allowing concurrently the existence of a family of chimera states, which are organized by a homoclinic snaking bifurcation diagram.
10.1103/PhysRevE.93.052204
pubmed_176_11995
While previous research has suggested that music training is associated with improvements in various cognitive and linguistic skills, the mechanisms mediating or underlying these associations are mostly unknown. Here, we addressed the hypothesis that previous music training is related to improved working memory. Using event-related potentials (ERPs) and a standardized test of working memory, we investigated both neural and behavioral aspects of working memory in college-aged, non-professional musicians and non-musicians. Behaviorally, musicians outperformed non-musicians on standardized subtests of visual, phonological, and executive memory. ERPs were recorded in standard auditory and visual oddball paradigms (participants responded to infrequent deviant stimuli embedded in lists of standard stimuli). Electrophysiologically, musicians demonstrated faster updating of working memory (shorter latency P300s) in both the auditory and visual domains and musicians allocated more neural resources to auditory stimuli (larger amplitude P300), showing increased sensitivity to the auditory standard/deviant difference and less effortful updating of auditory working memory. These findings demonstrate that long-term music training is related to improvements in working memory, in both the auditory and visual domains and in terms of both behavioral and ERP measures.
10.1016/j.neuropsychologia.2011.02.001
pubmed_186_16358
BACKGROUND Point-prevalence studies can identify priorities for infection control. AIM In May 2014, the Beijing Nosocomial Infection Control and Quality Improvement Centre organized a point-prevalence survey in 124 acute care hospitals in Beijing province. By analysing the survey results and factors affecting the point prevalence of healthcare-associated infections (HCAIs) in secondary and tertiary acute care hospitals in a certain area of China, this study provides evidence and reference to monitor HCAIs in a wide variety of hospitals. METHODS An epidemiological cross-sectional survey conducted by infection control practitioners was used to assess the point-prevalence rate of HCAIs by reviewing cases and performing bedside surveys. FINDINGS In total, 124 hospitals and 61,990 patients were surveyed, and 1389 (2.2%) HCAIs were diagnosed in 1294 (2.1%) patients. Respiratory tract infections were the most common HCAIs (54.4%, 51.7-56.9%), followed by urinary tract infections (15.0%, 13.2-16.9%), gastrointestinal tract infections (7.7%, 6.3-9.1%), surgical site infections (6.3%, 5.1-7.6%) and bloodstream infections (5.5%, 4.3-6.8%). In this survey, the top three pathogens were Pseudomonas aeruginosa, Acinetobacter baumannii and Escherichia coli. Rates of central vein catheter insertion, urethral catheterization and mechanical ventilation were 9.9%, 12.4% and 3.8%, respectively. Overall, 23.7% of the patients underwent surgery on or before the date of the survey. HCAIs were present in 14.5% of intensive care unit patients, 2.3% of medical patients and 2% of surgical patients. Diarrhoea was found in 0.8% of the assessed cases; however, tests for Clostridium difficile are not routinely available in China. CONCLUSION In areas with limited personnel and resources, regular investigation of the point prevalence of HCAIs can be performed in lieu of comprehensive monitoring to elucidate risk factors and disease burdens of HCAIs.
pubmed_186_16358
pubmed_1051_5113
Background and Objectives: Smartphone use has been rapidly increasing worldwide, which has brought possible smartphone addiction into the focus of research. In order to identify potential smartphone addicts, several scales were developed to assess smartphone addiction. Among them, the Smartphone Addiction Scale was frequently used. The study aimed to test the reliability and validity of the Serbian version of the SAS-SV and estimate smartphone addiction prevalence among medical students. Materials and Methods: The study was conducted in December 2018 on a convenience sample of 323 third-year medical students. The cross-cultural adaptation was performed following the well-established guidelines for cross-cultural adaptation of self-reported measures. Exploratory factor analysis was used to examine the structure of the questionnaire. Factor extraction was performed by principal component analysis with Varimax rotation. For test-retest reliability, students completed the questionnaire twice within seven days. Results: The Serbian version of the SAS-SV showed good internal consistency (Cronbach's alpha = 0.89) and excellent reliability for test-retest scores (ICC = 0.94, 95% CI = 0.92-0.96). Factor analysis supported the extraction of one factor, which explained 51.538% of the variance. To explore convergent validity furthermore, the SAS-SV was correlated with time indicators of smartphone use. According to cut-off values for the SAS-SV score, 19.5% of students could be regarded as "addicted", and often spent more time on smartphones and social networks on working days and weekends than "not addicted" students. Conclusions: The Serbian version of the SAS-SV is a reliable and valid instrument for detecting smartphone addiction among university students. Further research on this issue is encouraged to enable a better understanding of this ever-increasing public health issue.
10.3390/ijerph19031245
pubmed_291_7493
As the number of migrants,- forced or voluntary,- increases, there is a growing need to understand how negative events in the country of origin influence those residing abroad. This issue has been actualized by the recent earthquakes in Haiti and Chile. Persons in exile have frequently been exposed to severe human rights violations and other stressors prior to emigration. The present study explored possible associations between ongoing and former stressors and mental health problems among persons living in exile as the Tsunami disaster of 2004 struck their country of origin. The contribution of former exposure and exilerelated difficulties in explaining current mental health problems was explored together with Tsunami related bereavement and social support. Following the Tsunami disaster of 2004 a questionnaire was administered to individuals of Tamil and Acehnese origin residing in Norway. The results suggest an independent contribution of exilerelated difficulties, former exposure and social support in explaining current mental health problems in this group. The study also disclosed methodological challenges involved both in relation to recruiting participants and in isolating the contribution of a particular stressor in populations with high levels of former exposure as well as ongoing stress.
pubmed_291_7493
pubmed_118_23831
BACKGROUND AND PURPOSE Progression of asymptomatic carotid artery stenosis (ACAS) in patients with >50% luminal narrowing is considered a potential risk factor for ischemic stroke; however, subclinical molecular biomarkers of ACAS progression are lacking. Recent studies suggest a regulatory function for several microRNAs (miRNAs) on the evolution of carotid plaque, but its role in ACAS progression is mostly unknown. The aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS to associate circulating miRNA expression profiles with stenosis progression. METHODS The study included 60 patients with ACAS carrying >50% luminal narrowing. First, miRNA expression profiles of circulating exosomes were determined by Affymetrix microarrays from plasma samples of 16 patients from the cohort. Second, those miRNAs among the most differentially expressed in patients with ACAS progression were quantified by real-time polymerase chain reaction in a separate replication cohort of 39 subjects within the patient sample. RESULTS Our results showed that ACAS progression was associated with development of stroke. MiR-199b-3p, miR-27b-3p, miR-130a-3p, miR-221-3p, and miR-24-3p presented significant higher expression in those patients with ACAS progression. CONCLUSIONS In conclusion, our study supports that specific circulating miRNA expression profiles could provide a new tool that complements the monitoring of ACAS progression, improving therapeutic approaches to prevent ischemic stroke.
10.1161/STROKEAHA.116.013650
pubmed_475_4879
OBJECTIVE One-quarter of deaths in children with chronic renal failure is due to cardiovascular complications. Conventional echocardiographic methods are insufficient for evaluating systolic functions in children with chronic renal failure. The aim of the present study was to investigate cardiac functions in children with chronic renal failure by evaluating left atrial volume and functions. METHODS The present cross-sectional observational study included 44 children undergoing dialysis, 16 children with chronic renal failure but not yet on dialysis, and 20 healthy control subjects. Transthoracic echocardiography was performed for all children. Variables regarding to left ventricle and atrium (left atrial systolic force, left atrial systolic force index, left atrial volume, left ventricular mass index, and relative wall thickness) were measured using two-dimensional and M-mode echocardiography. RESULTS Left atrial systolic force index was negatively correlated with systolic blood pressure and left ventricular mass (p=0.01, r=0.266 and p=0.02, r=0.347, respectively). However, it was positively correlated with both early and late diastolic mitral inflow velocity (r=0.518, p=0.001 and r=0.828, p=0.001, respectively). There were no significant difference among the groups in terms of left atrial systolic force index and left atrial volume. However, left atrial systolic force index was higher in children with chronic renal failure but not yet on dialysis. CONCLUSION Left atrial systolic force was negatively correlated with systolic blood pressure and left ventricular mass. These findings suggested that evaluating left atrial systolic force and left atrial volume were useful to determine diastolic dysfunction and the necessity of dialysis in patient with chronic renal failure.
10.5152/akd.2014.4675
pubmed_56_12607
The survival of patients with hematological malignancies has been significantly improved due to the development of new therapeutic agents. However, relapse remains a major matter for concern. Recently, T cells engineered with chimeric antigen receptor (CAR) were reported to show unprecedented responses in a range of hematological malignancies. The persistence of the CAR-T cell can last for years and tends toward long-term antitumor memory by which relapses can be effectively prevented. The primary side effects that appear in most clinical trials are cytokine release syndrome and neurotoxicity. However, these symptoms can be treated and reversed. In this review, we describe CAR structure and function and summarize recent advances in CAR-T cell therapy in hematological malignancies.
10.1007/s11427-016-5036-3
pubmed_916_25245
BACKGROUND Migrant women in sex work experience unique risks and protective factors related to their sexual health. Given the dearth of knowledge in high-income countries, we explored factors associated with inconsistent condom use by clients among migrant female sex workers over time in Vancouver, BC. METHODS Questionnaire and HIV/sexually transmitted infection testing data from a longitudinal cohort, An Evaluation of Sex Workers Health Access, were collected from 2010 to 2013. Logistic regression using generalized estimating equations was used to model correlates of inconsistent condom use by clients among international migrant sex workers over a 3-year study period. RESULTS Of 685 participants, analyses were restricted to 182 (27%) international migrants who primarily originated from China. In multivariate generalized estimating equations analyses, difficulty accessing condoms (adjusted odds ratio [AOR], 3.76; 95% confidence interval [CI], 1.13-12.47) independently correlated with increased odds of inconsistent condom use by clients. Servicing clients in indoor sex work establishments (e.g., massage parlors) (AOR, 0.34; 95% CI, 0.15-0.77), and high school attainment (AOR, 0.22; 95% CI, 0.09-0.50) had independent protective effects on the odds of inconsistent condom use by clients. CONCLUSIONS Findings of this longitudinal study highlight the persistent challenges faced by migrant sex workers in terms of accessing and using condoms. Migrant sex workers who experienced difficulty in accessing condoms were more than 3 times as likely to report inconsistent condom use by clients. Laws, policies, and programs promoting access to safer, decriminalized indoor work environments remain urgently needed to promote health, safety, and human rights for migrant workers in the sex industry.
10.1097/OLQ.0000000000000276
pubmed_358_5584
Drug users with chronic hepatitis C virus (HCV) infection are frequently co-infected with human immunodeficiency virus-1 (HIV-1), but it is still not clear whether HIV-1 worsens the natural history of hepatitis C. To investigate this, we conducted a multicentre observational study in 163 drug addicts with histologically documented hepatitis C, 92 of whom were also infected with HIV-1: 25 (27%) were CDC stage II, 53 (58%) were CDC stage III and 14 (15%) were CDC stage IV. Eighty-eight (54%) patients had chronic hepatitis (CH) with minimal activity, 28 (17%) had CH with moderate activity, 40 (25%) had CH with severe activity and seven (4%) had active cirrhosis. Twenty-one HIV-negative patients and 15 HIV-positive patients admitted to alcohol abuse (29% vs 16%, P=0.0665). Liver disease was more severe in HIV-positive patients than in HIV-negative ones (P=0.0198): 34 HIV-positive patients and 13 HIV negatives had severe CH and cirrhosis. These two severe liver diseases were seen more often in HIV-positive patients with a history of alcohol abuse than in HIV-negative patients (10 out of 16 vs seven out of 21). Age, alcohol abuse and distribution of the histological categories of liver disease were statistically different in HIV-infected and HIV-uninfected patients. Multivariate analysis showed that age, alcohol abuse and serum antibodies to HIV were independently associated with severe CH or cirrhosis. Thus, HIV may enhance the risk of severe liver disease in drug users with hepatitis C, independently of the degree of immune dysfunction. Alcohol abuse may contribute independently, aggravating the cause of HCV-dependent liver disease.
10.1046/j.1365-2893.2000.00230.x
pubmed_354_23385
The Social Responsiveness Scale (SRS) has been validated in high-income countries but not yet in low- and middle-income countries. We aimed to assess the reliability of the SRS in a community sample and its validity to discriminate between children with and without autism spectrum disorder (ASD) in Vietnam. We used a three-phase study: piloting the translated SRS, reliability testing, and validation of the SRS in 158 Vietnamese caretakers and their children (ages 4-9 years). We examined reliability, validity and sensitivity, and specificity to ASD diagnosis. We applied receiver operator characteristic (ROC) analysis to determine optimal cutoff scores discriminating the children with ASD from those without ASD. We also assessed the performance of the SRS short form. We found that reliability was good with high internal consistency (0.88-0.89), test-retest reliability (0.82-0.83), sensitivity (93%), and specificity (98%) for identification of children with ASD. The ROC curves were similar for total raw score and total T-score, with the area under the curve (AUC) values reaching 0.98 and the optimal cutoff of 62 for raw scores and 60 for T-scores. The SRS short form also performed well in distinguishing children with ASD from children without ASD, with high AUC (0.98), sensitivity (90%), and specificity (98%) when using a raw score of 15 as a cutoff. In conclusion, the translated and culturally adapted SRS shows good reliability, validity, and sensitivity for identification of children with ASD in Vietnam. Both SRS long and short forms performed adequately to discriminate between children with and without ASD. Autism Res 2019, 00: 1-13. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Middle-income countries often lack validated tools to evaluate autism symptoms. The Social Responsiveness Scale (SRS) translated to Vietnamese was reliable and performed well to distinguish between children with and without autism spectrum disorder in Vietnam. The Vietnamese SRS, and translations of the tool to other languages with this methodology, may be useful in pediatric practice, potentially allowing providers to make more appropriate referrals for diagnostic evaluations and identify children for intervention to help them fulfill their developmental potential.
10.1002/aur.2179
pubmed_866_23088
Bivalves are one of the key components of the biogeochemical cycle in the marine system, and respond to heavy metal (HM) sensitively as filter feeders. To determine relationship of HMs in edible bivalve and seawater and HM effects on human health when digesting bivalves, HMs were analyzed in bivalves and seawater. The results showed that the mean HM concentrations in bivalves decreased in the order of Zn > Cu > Cr > Pb > As > Cd > Hg. Generally, all the bioconcentration factor values of bivalves were higher than 100, suggesting that bivalves have a high bioaccumulation ability. Nonmetric multidimensional scaling analysis indicated that all bivalves have a high bioaccumulation capacity for Cu and Zn. It was found that there are health risks associated with consuming bivalves, and children are more vulnerable than adults. Finally, the maximum allowable consumption rates of non-carcinogenic and carcinogenic risk were determined. These results provide the underlying insights needed to guide the consumption of seafood.
10.1016/j.marpolbul.2019.110717