We assessed and compared abiotic preferences of aquatic macroinvertebrates in three river basins located in Ecuador, Ethiopia and Vietnam. Upon using logistic regression models we analyzed the relationship between the probability of occurrence of five macroinvertebrate families, ranging from pollution tolerant to pollution sensitive,  and physical-chemical water quality conditions. Within the investigated physical-chemical ranges, nine out of twenty-five interaction effects were significant. Our analyses suggested river basin dependent associations between the macroinvertebrate families and the corresponding physical-chemical conditions. It was found that pollution tolerant families showed no clear abiotic preference and occurred at most sampling locations, i.e. Chironomidae were present in 91%, 84% and 93% of the samples taken in Ecuador, Ethiopia and Vietnam. Pollution sensitive families were strongly associated with dissolved oxygen and stream velocity, e.g. Leptophlebiidae were only present in 48%, 2% and 18% of the samples in Ecuador, Ethiopia and Vietnam. Despite some limitations in the study design, we concluded that associations between macroinvertebrates and abiotic conditions can be river basin-specific and hence are not automatically transferable across river basins in the tropics. Benthic macroinvertebrates have often been used for water quality monitoring and assessment Most macroinvertebrate-based water quality assessment methods have been developed in temperate climate regions where relationships between environmental variables and the occurrence of macroinvertebrate taxa are well documented. Due to the infancy of the macroinvertebrate-based monitoring and assessment in the tropics The aim of this study was to assess if abiotic preferences of aquatic macroinvertebrates differed between three river basins in the tropics. We investigated associations between physical-chemical variables and macroinvertebrate occurrences in one Ecuadorian, one Ethiopian and one Vietnamese river basin. Five representative macroinvertebrate taxa, ranging from pollution tolerant to pollution sensitive were selected and their preferences towards environmental conditions were compared using regression-based ecological models.−1), dissolved oxygen concentration (mg.L−1), pH (-), stream velocity (m.s−1) and water temperature (°C) (Samples were taken in the Chaguana river basin (Ecuador), Gilgel Gibe river basin (Ethiopia) and Cau river basin (Vietnam) –S3. In eure (°C) .Benthic macroinvertebrates were sampled, identified and quantified according to the method described in Gabriels et al. Boxplots were used for data exploration. The first series of boxplots visualized the seasonality of the physical-chemical variables per river basin. The second series of boxplots summarized for each macroinvertebrate family and per physical-chemical variable and river basin the conditions under which the taxon was present and absent. Boxplots were constructed with the R software The univariate associations between explanatory variables were assessed with pairwise Spearman's rank correlations, which is often used in ecology due to its nonparametric nature The occurrence of five macroinvertebrate families was related to the physical-chemical water quality conditions using a regression-based model and these relationships were compared between three river basins situated in the tropics. Logistic regression models (LRMs) were used to infer relationships between occurrences of five aquatic macroinvertebrate families and environmental data. LRMs have been frequently used to model the presence or absence of a species in relation to environmental variables A hierarchical backward elimination model selection method was carried out to build the LRM. The starting model included five physical-chemical variables , season and river basin (represented as country). In addition to the main effects, two-way interactions between the physical-chemical variables and the river basin as well as between season and river basin were included  and S2. Residual plots and the extended Hosmer-Lemeshow test for LRMs based on GEE The outcome of the LRM per family was visualized as the estimated probability that the family was present as a function of a physical-chemical variable. The explanatory variables different from the one on the x-axis, were set to their river basin specific medians and the season to “dry”. The river basin-specific observed range of the corresponding physical-chemical variable were plotted as horizontal boxplots below the response curves and were subdivided between presence and absence points. The gray-colored ends of the response curves indicate extrapolation outside the observed range of the corresponding physical-chemical variable.For the data exploration, the effects of season and river basin on the continuous physical-chemical variables were assessed using a linear regression model fitted with GEE for accounting for the clustered sampling scheme. Only few p-values were reported in the main text to prevent information overload, all p-values were summarized in The observed range of physical-chemical water quality conditions was not always equal between river basins. Seasonal effects were observed for all physical-chemical variables and the seasonal effect of conductivity and stream velocity was similar for the three river basins –S8. DissThe prevalence values, known as the relative frequencies of occurrence of taxa , i.e. the effect of water temperature on the occurrence differed between river basins . AlthougThe effect of water temperature on the probability of occurrence of Baetidae differed between river basins p<0.01; . Indeed,Associations between the DO concentration, pH, stream velocity and water temperature relative to the probability of occurrence of Hydroptilidae were similar across river basins . Only thThe associations between water temperature (p<0.01), stream velocity (p = 0.02) and DO concentration (p = 0.02) and the probability of occurrence of Libellulidae differed between river basins . WhereasAssociations between stream velocity  and S54,−1 for optimal health For pollution tolerant macroinvertebrate families (e.g. Chironomidae (TS2)) only few significant associations between physical-chemical conditions and the occurrence of the families were found  suggestiHabitat suitability of macro-invertebrates probably depends on more factors than those included in our statistical analysis. For instance, additional to the variables that were included in our analysis, Al-Shami et al. Seasonal changes of environmental variables were taken into account The outcome of the LRM per family was visualized as the estimated probability that the family was present as a function of a physical-chemical variable e.g. –5. WithiThe fact that river basin dependent associations were found is not surprising. For instance, Bonada et al. Since the range of the observed physical-chemical conditions were not always equal between river basins, in some cases extrapolations outside the observed range were shown . For insNo relation was found between the occurrence of Leptophlebiidae and stream velocity in the Ethiopian and the Vietnamese river basin. However, according to the data Leptophlebiidae occurred in both river basins in upstream sampling sites with a moderate to high stream velocity. The reason for the non-significant relation is the prevalence of the present-points. In the Vietnamese and Ethiopian river basin, Leptophlebiidae were only present in 18% and 2% of the samples, respectively. Consequently, the occurrence of Leptophlebiidae seems statistically not associated with stream velocity. Therefore, due to unbalanced dataset prevalence it is possible that not all models obtained represent true ecological relations Presence and absence data are commonly used in macroinvertebrate research e.g.,  as they As an alternative to the conventional taxonomic division of the benthic invertebrates one can use functional traits to categorize macroinvertebrate assemblages e.g., . Such a Overall, LRMs based on GEE are a flexible way to model the probability of occurrence of macroinvertebrates as a function of environmental variables. We revealed similar as well as dissimilar abiotic preferences of macroinvertebrates between the three river basins, but these estimated probabilities are restricted to the observed range of the predictor within each river basin. In conclusion we found that associations between macroinvertebrates and abiotic conditions can be river basin-specific.Figure S1Sampling sites in the Chaguana river basin in Ecuador.(DOCX)Click here for additional data file.Figure S2Sampling sites in the Gilgel Gibe river basin in Ethiopia.(DOCX)Click here for additional data file.Figure S3Sampling sites in the Cau river basin in Vietnam.(DOCX)Click here for additional data file.Figure S4Boxplots showing the seasonality (dry (blue) and wet (red) season) of the stream velocity.(DOCX)Click here for additional data file.Figure S5Boxplots showing the seasonality (dry (blue) and wet (red) season) of the water temperature.(DOCX)Click here for additional data file.Figure S6Boxplots showing the seasonality (dry (blue) and wet (red) season) of the conductivity.(DOCX)Click here for additional data file.Figure S7Boxplots showing the seasonality (dry (blue) and wet (red) season) of the pH.(DOCX)Click here for additional data file.Figure S8Boxplots showing the seasonality (dry (blue) and wet (red) season) of the dissolved oxygen.(DOCX)Click here for additional data file.Figure S9Boxplots indicate the observed stream velocity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Chironomidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S10Boxplots indicate the observed water temperature in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Chironomidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S11Boxplots indicate the observed conductivity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Chironomidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S12Boxplots indicate the observed pH in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Chironomidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S13Boxplots indicate the observed DO concentrations in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Chironomidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S14Boxplots indicate the observed stream velocity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Baetidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S15Boxplots indicate the observed water temperature in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Baetidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S16Boxplots indicate the observed conductivity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Baetidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S17Boxplots indicate the observed pH in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Baetidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S18Boxplots indicate the observed DO concentrations in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Baetidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S19Boxplots indicate the observed stream velocity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Hydroptilidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis).(DOCX)Click here for additional data file.Figure S20Boxplots indicate the observed water temperature in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Hydroptilidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S21Boxplots indicate the observed conductivity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Hydroptilidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S22Bottom: Boxplots indicate the observed pH in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Hydroptilidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis).(DOCX)Click here for additional data file.Figure S23Boxplots indicate the observed DO concentrations in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Hydroptilidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S24Boxplots indicate the observed stream velocity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Libellulidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S25Boxplots indicate the observed water temperature in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Libellulidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S26Boxplots indicate the observed conductivity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Libellulidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S27Boxplots indicate the observed pH in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Libellulidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S28Boxplots indicate the observed DO concentrations in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Libellulidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S29Boxplots indicate the observed stream velocity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Leptophlebiidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S30Boxplots indicate the observed water temperature in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Leptophlebiidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S31Boxplots indicate the observed conductivity in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Leptophlebiidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis).(DOCX)Click here for additional data file.Figure S32Boxplots indicate the observed pH in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Leptophlebiidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S33Boxplots indicate the observed DO concentrations in Ecuador (red), Ethiopia (green) and Vietnam (blue) at which Leptophlebiidae are found to be present (denoted by P on the left axis) and absent (denoted by A on the left axis). The sample sizes per boxplot are shown on the right axis.(DOCX)Click here for additional data file.Figure S34The probability of Chironomidae being present in relation to the stream velocity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S35The probability of Chironomidae being present in relation to the water temperature measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S36The probability of Chironomidae being present in relation to the conductivity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S37The probability of Chironomidae being present in relation to the pH measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S38The probability of Chironomidae being present in relation to dissolved oxygen (DO) concentration measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S39The probability of Baetidae being present in relation to stream velocity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S40The probability of Baetidae being present in relation to water temperature measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S41The probability of Baetidae being present in relation to conductivity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S42The probability of Baetidae being present in relation to pH measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S43The probability of Baetidae being present in relation to dissolved oxygen (DO) concentration measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S44The probability of Hydroptilidae being present in relation to stream velocity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S45The probability of Chironomidae being present in relation to the Hydroptilidae measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S46The probability of Hydroptilidae being present in relation to the conductivity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S47The probability of Hydroptilidae being present in relation to pH measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S48The probability of Hydroptilidae being present in relation to dissolved oxygen (DO) concentration measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S49The probability of Libellulidae being present in relation to stream velocity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S50The probability of Libellulidae being present in relation to the water temperature measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S51The probability of Libellulidae being present in relation to the conductivity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S52The probability of Libellulidae being present in relation to pH measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S53The probability of Libellulidae being present in relation to dissolved oxygen (DO) concentration measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S54The probability of Leptophlebiidae being present in relation to stream velocity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S55The probability of Leptophlebiidae being present in relation to the water temperature measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S56The probability of Leptophlebiidae being present in relation to the conductivity measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S57The probability of Leptophlebiidae being present in relation to pH measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Figure S58The probability of Leptophlebiidae being present in relation to dissolved oxygen (DO) concentration measured in Ecuador , Ethiopia  and Vietnam . The gray-colored ends of the response curves indicate extrapolation outside the observed physical-chemical range in the corresponding river basin.(DOCX)Click here for additional data file.Table S1Seasonal differences per physical-chemical variable and per country. A p-value less than 0.05 demonstrates a significant difference between seasons for the mean physical-chemical variable that is considered for a specific country. Significant relations are indicated in bold.(DOCX)Click here for additional data file.Table S2Country-wise differences per physical-chemical variable and per season. A p-value less than 0.05 demonstrates a significant difference between countries for the mean physical-chemical variable that is considered for a specific season. Significant relations are indicated in bold.(DOCX)Click here for additional data file.


Diabetic polyneuropathy (DPN) has an insidious and non-homogeneous installation making it difficult to determine its onset. Therapeutic and preventive actions should target patients depending on their DPN severity status. Methods for supporting the decision making process of classifying patients can improve early health actions.Analyze the use of 2 artificial intelligence methods for classifying the DPN severity degree: (a) fuzzy modeling and (b) multiple correspondence analysis (MCA) and Kohonen map.Retrospective analysis of 195 patients. The fuzzy model determined a DPN degree score (0-10) by the combination of fuzzy sets derived from clinical variables , using if-then rules to combine the inputs with the output sets (Mamdani process), with membership functions determined by a team of 4 DPN specialists. The MCA method grouped 16 DPN-related categorical variables  into micro and macro-classes (groups) after the algorithm learned the grouping pattern of the variables in the patients' cohort. A Kohonen map was used to better represent the clusters of variables that could identify different DPN severities.Loss of tactile and vibration perceptions were decisive for classification of DPN severity using the fuzzy system, and its sensitivity and specificity in discriminating patients with and without DPN was very high (ROC=0.985). The MCA and Kohonen map identified 4 macro-classes of variables: (1) DPN absence, (2 and 3) intermediate status , and (4) severe .The fuzzy model contributes to the early detection of DPN using typical clinical variables, and although this method strongly relies on the specialist subjectivity, it is very reliable. Software for classifying DPN severity using this Fuzzy model is available and can be easily implemented in any clinical setting as a decision support system. The MCA


The still unclear mechanisms causing ventilator-induced diaphragm dysfunction (VIDD) are considered intrinsic to the diaphragm muscle fibers. VIDD delays and complicates weaning from mechanical ventilation (MV) and accordingly contributes to prolonged ICU stay by 50%, with older patients being more affected than the young. The main aim of this study was to measure the effects of aging and 5 days of MV on rat diaphragm muscle fiber structure and function. We also aimed to investigate the biological age of the old rats to obtain data useful to design future experimental studies focusing on the effects of age in an ICU setting.We used a unique ICU rat model, which allows us to maintain the vital parameters stable under deep sedation and MV for long durations . Diaphragm fiber cross-sectional area (CSA) and force-generating capacity (specific force = absolute force / CSA) were measured in young (6 months) and old (28 to 32 months) F344/ BN hybrid rats in response to 5 days of deep sedation and volume-controlled MV. To investigate the biological age of the old rats, we performed a second set of experiments, comparing muscle fiber CSA and specific force in fast and slow-twitch distal hind limb muscles in three different age groups: young adults (6 months), middle aged (18 months) and old rats (28 months).P < 0.001) of the diaphragm fibers in response to 5 days of MV in both young and old animals. Maximum force decreased 39.8 to 45.2% (P < 0.001) in both young and old animals compared with controls, resulting in a dramatic loss of specific force. This increase in CSA and the concomitant decrease in specific force observed in both young and old diaphragm fibers are compatible with an ineffective compensatory hypertrophy in response to the MV. The comparison of the limb muscles fibers from young, middle aged and old animals confirmed the 28 to 32 month rats to be senescent from a skeletal muscle point of view.This study demonstrated an unexpected increase in CSA (These results demonstrate intrinsic changes in diaphragm muscle fibers of significant importance for the prolonged and complicated weaning from MV. Moreover, the increased number of frail diaphragm muscle fibers observed after MV in old age, both controls and mechanically ventilated, offers a further age-related possible mechanism which may be of significant clinical importance. These results also provided useful information to design future experimental studies focused on the effect of age in an ICU setting, pharmacological intervention strategies as well as mechanisms underlying rat strain differences.


The objectives of the study were (1) to explore the pattern of public spending on road safety programmes corresponding to 5-E strategy , and (2) to investigate road safety policy directions.The government budget documents from 5 ministries including Ministry of Transport, Education, Interior, Public Health and Royal Thai Police were reviewed. Two researchers identified budget used in road safety projects with 5-E strategies independently; the kappa analysis was used to test inter-rater reliability. Information from Thai Health Promotion Foundation and Road Safety Fund was also gathered using a developed excel-based template. Semi-structured interviews were conducted among road safety experts. Some mathematical and statistical analyses were applied to evaluate the efficiency of road safety policy.Thailand devoted around 18 billion Baht each year to prevent road traffic accidents. The majority of public budget was allocated to engineering strategies (50%), followed by enforcement (23%), emergency medical services (12%), evaluation (8%) and education (7%). The road safety experts, however, suggested that the strategies of education, enforcement and particularly evaluation are Thailand‘s key success factors. Thus, an area-based road safety information system should be developed. Data Envelopment Analysis suggested an inefficiency of law-enforcement system in Thailand by comparison with other countries worldwide.Despite insufficient data and evidence to clarify the outcomes of road safety policy and programmes, it is possible to conclude that (1) there is an underinvestment in road safety in Thailand and (2) the government allocates budget inappropriately. This study suggests allocating more public spending on road safety management data systems that empower local service providers to access and analyse current accident information. Investing in strategies of education and enforcement effectively influencing road user behaviour would be the right way to achieve the ultimate goal.


Even with the availability of new and more effective diagnostic procedures over the past decades, autopsy remains one of the most reliable methods to validate clinical diagnoses. The aim of this review was to determine whether autopsy plays a role in extending knowledge about the cause of death in patients with cirrhosis who died in the ICU.We conducted a retrospective review of medical records and postmortem findings in critically ill patients with cirrhosis who were admitted to a major university teaching medical ICU (MICU) between August 2007 and August 2013. Agreement between diagnoses before death and postmortem findings were compared using the Goldman system [n = 19, 45%).Of 641 patients admitted with diagnosis of cirrhosis, 86 (13%) died in the MICU. Forty-five (52%) patients underwent an autopsy. Forty-two autopsy reports were available for review, three histologic and microbiological reports were missing. Major missed diagnoses  were present in seven patients (17%), four in class I (10%) and three in class II (7%) (Table Despite declining rates worldwide, autopsy remains an important tool for quality and safety assurance. In this retrospective study, autopsy showed that knowledge of the correct premortem diagnosis would have altered therapy in 10% of critically ill cirrhotic patients.


There is an error in the first sentence of the Introduction. The correct sentence is: Behavioral studies indicate involvement of the prefrontal cortex and medial temporal lobe (MTL) during memory tasks that require short-term (200ms- 30s) information retention [1–4]. The publisher apologizes for this error.


There are errors in Equation (3). In the description of Equation (3), the equilibrium frequencies PIX are incorrectly defined in terms of pi, where in fact they should be defined in terms of phi. Please see the corrected description of Equation (3) here.


The differential diagnosis of hypertrophic phenotype remains challenging in clinical practice, in particular between hypertrophy cardiomyopathy (HCM) and increased left ventricular wall thickness (LVWT) due to systemic hypertension. Diffuse myocardial fibrosis is the characteristic feature in HCM, whereas hypertensive response is underpinned by addition of myofibrils in otherwise normal myocardial tissue. Late gadolinium enhancement (LGE) imaging provided important new way of differentiation between these two entities by separating those cases with evidence of regional fibrosis. Whereas approximately 60% of patients with HCM reveal visually discernable LGE, T1 mapping is highly discriminative, irrespective of the presence of LGE.Sixty patients with diagnosis of unequivocally hypertrophic cardiomyopathy and fifty patients with hypertensive cardiomyopathy underwent routine cardiac MRI protocol including assessment of function and scar (3-Tesla). T1 values were measured conservatively within septal myocardium in midventricular short-axis slice prior to administration of 0.2 mmol/kg of gadobutrol.HCM group showed higher LV mass and maximum LVWT than the hypertensive group . There was LGE in 20% of hypertensive  and in 84% of hypertrophic cardiomyopathy  (p < 0.001). Patients with HCM showed significantly higher T1 values compared to hypertensive patients . Native T1 values were concordant to LVWT and LV mass . T1native held superior diagnostic accuracy compared to conventional functional parameters and the presence of LGE to discriminate between hypertrophic or hypertensive cardiomyopathy  comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital National Health Service Foundation Trust. Dr. Rocio Hinojar was supported by the Fundacion Alfonso Martin Escudero.


Hyperfibrinolysis (HF) is a major issue of trauma-induced coagulopathy but has also been described in many other medical or surgical settings such as cardiopulmonary surgery, gastro-intestinal bleeding, liver transplantation and post-partum hemorrhage.The aim of this study was to describe the HF in a cohort of patients experiencing severe bleeding from trauma and non-trauma source and to highlight the differences between both groups.®) between 2010 and 2014 were included. Demographic and clinical parameters, standard laboratory and ROTEM® results were collected. HF diagnosis was established when the 60 minute clot lysis index (CLI60) was below 85% of the maximum clot firmness. HF was classified as fulminant HF (immediate breakdown of the clot within 30 minutes), intermediate HF (breakdown of the clot between 30 and 60 minutes) and late HF (complete clot lysis after more than 60 minutes). Data are expressed as n (%) and median [interquartile range].We conducted an observational, retrospective study in two academic trauma centers from a French university institution. All patients diagnosed with HF on rotational thromboelastometry (ROTEMSixty-four patients were included (39 trauma and 25 non trauma). Overall mortality was 64% . Median ISS for trauma patients was 49 . Patients severity assessed with SAPS II was not different between groups  whereas 28 day survival was greater in non-trauma patients  (Figure  to 73 vsFulminant HF is more frequent in trauma patients and is associated with an increased mortality. The decreasing incidence of HF observed during the study period might be due to the systematic prehospital administration of tranexamic acid in trauma patients since 2011 in our city area.


Virus replication efficiency is influenced by two conflicting factors, kinetics of the cellular interferon (IFN) response and induction of an antiviral state versus speed of virus replication and virus-induced inhibition of the IFN response. Disablement of a virus's capacity to circumvent the IFN response enables both basic research and various practical applications. However, such IFN-sensitive viruses can be difficult to grow to high-titer in cells that produce and respond to IFN. The current default option for growing IFN-sensitive viruses is restricted to a limited selection of cell-lines (e.g. Vero cells) that have lost their ability to produce IFN. This study demonstrates that supplementing tissue-culture medium with an IFN inhibitor provides a simple, effective and flexible approach to increase the growth of IFN-sensitive viruses in a cell-line of choice. We report that IFN inhibitors targeting components of the IFN response  significantly increased virus replication. More specifically, the JAK1/2 inhibitor Ruxolitinib enhances the growth of viruses that are sensitive to IFN due to (i) loss of function of the viral IFN antagonist (due to mutation or species-specific constraints) or (ii) mutations/host cell constraints that slow virus spread such that it can be controlled by the IFN response. This was demonstrated for a variety of viruses, including, viruses with disabled IFN antagonists that represent live-attenuated vaccine candidates , Influenza Virus), traditionally attenuated vaccine strains  and a slow-growing wild-type virus (RSV). In conclusion, supplementing tissue culture-medium with an IFN inhibitor to increase the growth of IFN-sensitive viruses in a cell-line of choice represents an approach, which is broadly applicable to research investigating the importance of the IFN response in controlling virus infections and has utility in a number of practical applications including vaccine and oncolytic virus production, virus diagnostics and techniques to isolate newly emerging viruses. Knockout of viral IFN antagonists is also a method of engineering viruses to specifically target cancer cells for oncolytic virotherapy Virus infection triggers the cellular interferon (IFN) response to produce Type 1 IFN's alpha and beta (IFNα/β). Secreted IFNα/β can stimulate the JAK-STAT pathway in an autocrine or paracrine manner to activate hundreds of IFN-stimulated genes (ISGs), many of which have antiviral activities that elicit an antiviral state Despite the advantages of disabling a virus's IFN antagonist, it can be difficult to grow such IFN-sensitive viruses to high-titer in tissue culture cells that produce and respond to IFN Inhibitors of the IFN response  were prepared as 10 mM stocks in dimethyl sulfoxide (DMSO) and used at the indicated concentrations. Inhibitors were purchased from Selleck Chemicals except MRT68844 and MRT67307, which were gifts of MRC-Technology and Philip Cohen (University of Dundee) respectively. Cell-lines derived from a variety of mammalian species were utilized: human (A549 and MRC5) monkey (Vero), mouse , rabbit (RK13), dog (MDCK) and pig (PKIBRS2). These cells were obtained from the European Collection of Cell Cultures (ECACC) with the exception of the PKIBRS2 cells, which were obtained from the Institute of Animal Health (UK) 4 units/ml of purified α-IFN  to activate the IFN signaling pathway and GFP expression from the IFN response (ISRE) promoter. Forty-eight hours post-IFN stimulation GFP expression and cellular cytotoxicity were measured as described above. Each assay was conducted in triplicate and the mean and standard deviation (StDev) determined.The A549/pr(IFN-β).GFP and A549/pr(ISRE).GFP reporter cell-lines were used to test the effect of IFN inhibitors on IFN induction or IFN signaling. A549/pr(IFN-β).GFP were seeded into a 96 well plate and media supplemented with a TBK1 inhibitor  or the IKK2 inhibitor (TPCA-1) at the indicated concentrations or equivalent volumes of DMSO. Two hours post-inhibitor treatment cells were infected with a stock of PIV5VΔC rich in defective interfering particles (DIs) to optimally activate the IFN induction pathway and expression of GFP under the control of the IFN-β promoter Standard plaque assays were conducted in the appropriate cells using a 0.6% (w/v) avicell overlay Eight small molecules that have previously been described to inhibit the cellular IFN response were obtained; four inhibitors that target components of the IFN induction pathway: TBK1 inhibitors BX795, MRT68844, MRT67307 Bunyaviridae family are being developed as attenuated vaccines via NSs knockout Effect of the inhibitors on viral plaque formation was examined using A549 cells infected with recombinant Bunyamwera virus (BUNΔNSs), in which the NSs IFN antagonist has been inactivated rendering the virus IFN sensitive The six effective inhibitors were used to examine their effect on BUNΔNSs growth kinetics and all six inhibitors significantly improved virus titers . At 48 hWe next sought to determine if two inhibitors targeting different components of the IFN response could further boost BUNΔNSs growth if used in combination with each other or to supplement the medium of infected A549/PIV5-V cells. The IKK-2 inhibitor TPCA-1 and JAK1/2 inhibitor Ruxolitinib were tested. However combinations resulted in no further increases in plaque size in A549 cells and in fact a small decrease in plaque size was observed when the inhibitors were used in combination compared to Ruxolitinib or PIV5-V expressing cells alone . One posA limited number of cell-lines have regulatory approval for vaccine manufacture e.g. MRC5 Respiratory Syncytial Virus (RSV) and Influenza are examples of viruses currently being developed as IFN-sensitive attenuated vaccine candidates We also tested two traditional vaccine strains, measles (MeV) Edmonson and the Mumps (MuV) Enders, which have been generated empirically using nonsystematic attenuation methods in vitro. In the initial plaque formation screen the JAK1/2 inhibitor Ruxolitinib was the most effective and hence was taken forward for further study. Moreover, all the results obtained for Ruxolitinib were essentially mirrored with the IKK2 inhibitor TPCA-1 (data not shown). The plaque assays and growth curves performed required incubation with the inhibitor for multiple days. To ensure our results were not affected by loss of activity of the drug, we used the A549/pr(IFN-β).GFP and A549/pr(ISRE)GFP reporter cell-lines to measure the activity of the drug over time; confirming that the inhibitory effect of both Ruxolitinib and TPCA-1 was stable up to at least 7 days in tissue-culture  the cost of the inhibitor and (ii) the harvested virus stocks will contain the inhibitor which may affect experiments to address both basic science questions and regulatory problems for medical applications in humans, although in this latter regard it is noteworthy that Ruxolitinib is approved for clinical treatment of myelofibrosis in vivo, they may also prove useful in studies designed to investigate the importance of the IFN response in controlling virus infections in animal models.These results provide proof of principle that supplementing tissue-culture medium with IFN inhibitors provides a simple, effective and flexible approach to enhance virus growth in cell-lines of choice. IFN inhibitors targeting different components of the IFN response  significantly increased replication and yield of a variety of viruses; including examples of potential vaccine candidates with disabled IFN antagonists , traditionally attenuated vaccine strains  and wild-type viruses . In addition JAK1 inhibitors have recently been shown to enhance the growth of oncolytic vesicular stomatitis virus (VSV) in cancer cells resistant to oncolysis


The genes encoding the E3 ubiquitin protein ligase Parkin (PARK2) and the mitochondrial serine/threonine kinase PINK1 (PARK6) are mutated in clinically similar, autosomal recessive early onset Parkinson’s disease (PD) forms. Over the past ten years, a number of studies in different model systems have demonstrated that PINK1 and Parkin regulate jointly several processes relevant to maintenance of mitochondrial quality, including mitochondrial trafficking and dynamics, mitophagy and biogenesis. By using a combination of approaches of cell biology, confocal imaging and biochemistry in different cell models, we recently showed that loss of protein import efficiency triggers recruitment of Parkin by PINK1 in proximity of the translocase of outer mitochondrial membrane (TOM). We provided evidence that the degradation of specific TOM subunits plays a key role in initiating the autophagic degradation of damaged mitochondria. We also showed that PINK1 and Parkin interact with the TOM machinery on polarized mitochondria. Our results suggests that this interaction modulates the import of the multifunctional mitochondrion-protective matrix enzyme 17beta-hydroxysteroid dehydrogenase 10, which is depleted in Parkin-deficient mice and Parkinson’s disease patients. Electron and confocal microscopy, and calcium imaging approaches used to characterize the endoplasmic reticulum (ER)-mitochondria interface, a compartment previously linked to neurodegenerative processes, revealed enhanced juxtaposition between these organelles, associated with increased ER-to-mitochondria calcium transfer in cells from Parkin-deficient mice and patients with PARK2 mutations. Our current work aims at investigating the relevance of mitochondrial quality control mechanisms regulated by PINK1 and Parkin in different cell types of the central nervous system, to evaluate the contribution of each of them to the physiopathology of autosomal recessive Parkinson’s disease.


Observation of the kinetics of tissue enhancement after the injection of a bolus of tracer has been used for the analysis of perfusion and related variables. In general, a gradient of concentration in the exchanging vascular compartment between the arterial and venous ends is represented in models via focus on maintaining the detailed balance between the advective and diffusive exchange processes. Conventionally, this is by considering the exchange in an Eulerian framework, based on considering the exchange within each compartment as a separate unit  model ). HereinEight patients (age 63 ± 12 years) underwent first-pass perfusion (FPP) rest and regadenoson stress cardiac MRI (CMR) , followed by invasive coronary angiography. Images were obtained at 4 slice locations  and 3 short-axis slices of the left ventricle for the wall) using a TurboFLASH readout with centric k-space reordering [The results of a representative patient (66 year old man) with history of hypertension, hyperlipidemia, Diabetes Mellitus and known coronary artery disease with prior stents on maximal medical therapy are shown in Figure A novel method combining aspects of TH model and a Lagrangian approach allows quantification of the transit of tracer through myocardial tissue, and may serve to identify physiologically significant coronary artery disease. Larger studies to validate this approach are warranted.NIH R01 HL083309.


Atherosclerosis, a chronic inflammatory disorder of the arteries, is responsible for most deaths in westernized societies with numbers increasing at a marked rate in developing countries. The disease is initiated by the activation of the endothelium by various risk factors leading to chemokine-mediated recruitment of immune cells. The uptake of modified lipoproteins by macrophages along with defective cholesterol efflux gives rise to foam cells associated with the fatty streak in the early phase of the disease. As the disease progresses, complex fibrotic plaques are produced as a result of lysis of foam cells, migration and proliferation of vascular smooth muscle cells and continued inflammatory response. Such plaques are stabilized by the extracellular matrix produced by smooth muscle cells and destabilized by matrix metalloproteinase from macrophages. Rupture of unstable plaques and subsequent thrombosis leads to clinical complications such as myocardial infarction. Cytokines are involved in all stages of atherosclerosis and have a profound influence on the pathogenesis of this disease. This review will describe our current understanding of the roles of different cytokines in atherosclerosis together with therapeutic approaches aimed at manipulating their actions. Atherosclerosis is now recognized as an inflammatory disorder of medium and large arteries initiated by risk factors such as high plasma cholesterol levels and hypertension in vitro studies using cell culture model systems have made a major contribution in advancing our understanding of the roles of cytokines in the cellular processes associated with atherosclerosis, the major focus of this review will be on the outcome from studies using animal model systems. In particular, two mouse models, the apolipoprotein (Apo) E-deficient mice and the low-density lipoprotein receptor (LDLr)-deficient mice Cytokines are a diverse group of low-molecular weight proteins with over 100 identified so far. Cytokines are clustered into several classes such as the interleukins (IL), chemokines, colony-stimulating factors (CSF), tumor necrosis factors (TNF), the interferons (IFN) and transforming growth factors (TGF) 2Atherosclerotic plaques tend to form particularly at the inner curvatures and branch points of arteries that are often associated with disturbed blood flow, and is augmented by other factors such as high plasma low-density lipoprotein (LDL) concentration, hypertension and toxins from cigarette smoke The activated ECs release a range of chemokines and other cytokines that then cause the recruitment of circulating immune cells, particularly monocytes and T lymphocytes 3C, XC) high [express high levels of CC-chemokine receptor (CCR)-2, believed to be pro-inflammatory in nature and their levels increase in hyperlipidemia) and less frequent Ly6Clow [express CX3C-chemokine receptor 1 and perceived to carry out a homeostatic function) high monocytes involves immobilization of CCL5 and CXCL1 on proteoglycans and P-selectins on ECs Chemokines are a large family of structurally related, chemoattracting cytokines that are divided into subgroups on the basis of the position of the amino terminal cysteine residues  is also associated with reduced macrophage recruitment  and the alternatively activated M2 (thought to be derived from Ly6Clow-monocytes and produces anti-inflammatory cytokines such as IL-10 and TGF-β) that aid in the resolution of inflammatory responses −/− model system drives M2 macrophage polarization and inhibits atherosclerosis progression In the arterial intima, monocytes can differentiate to macrophages or dendritic cells (DCs) depending on the cytokine signal received with macrophage colony-stimulating factor (M-CSF) a major facilitator of macrophage differentiation LDL tends to diffuse passively through EC junctions and its retention is aided by interaction of its apoB moiety with components of the extracellular matrix such as proteoglycans Macrophages express pattern recognition receptors (PRRs), such as scavenger receptors (SRs), toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLR), that participate in foam cell formation and/or elicit an inflammatory response against foreign particles or endogenously produced danger signals in vivo; for example, IFN-γ and TNF-α promote this whereas IL-1RA and IL-33 are inhibitory. The formation of foam cells involves dysfunction of a homeostatic mechanism that controls the uptake, intracellular metabolism and efflux of cholesterol by macrophages −/− mice in vivo and macrophages in vitro by decreasing modified LDL uptake, reducing intracellular content of cholesteryl esters and stimulating cholesterol efflux As shown in 4Cholesterol is toxic to cells and mechanisms exist to maintain homeostasis. For example, derivatives of cholesterol, such as oxysterols, activate liver X receptors (LXRs) that then stimulate cholesterol efflux by inducing the expression of ABCA1 and ABCG1 Defective lipid homeostasis is instrumental in the amplification of the inflammatory response and activation of the immune response Antigen presenting cells, such as macrophages and DCs, are essential for the adaptive immune responses as they engulf and process antigens, and present them on the cell surface in association major histocompatibility complexes (MHC) for recognition by T-cells SMCs also play an important role in atherosclerosis and more advanced lesions are generally covered with a fibrous cap, composed of SMCs and ECM components produced by them, and lipid-rich necrotic core 5The continued inflammatory response ultimately leads to the destabilization of atherosclerotic plaques via the action of pro-inflammatory cytokines. Indeed, studies in mouse model systems have shown that IFN-γ, IL-18, GDF-15 and TWEAK destabilize plaques whereas TGF-β causes stabilization , Table 46Inflammation plays a pivotal role in all stages of atherosclerosis: endothelial dysfunction; recruitment of immune cells; modification of LDL; foam cell formation; apoptosis of foam cells; plaque rupture; and thrombosis. The inflammatory response in atherosclerosis is regulated by both the innate and adaptive immune system via the action of cytokines. Our understanding of the roles of such cytokines has recently advanced considerably mainly via studies using mouse model systems  None.


India’s agricultural output, economy, and societal well-being are strappingly dependent on the stability of summer monsoon rainfall, its variability and extremes. Spatial aggregate of intensity and frequency of extreme rainfall events over Central India are significantly increasing, while at local scale they are spatially non-uniform with increasing spatial variability. The reasons behind such increase in spatial variability of extremes are poorly understood and the trends in mean monsoon rainfall have been greatly overlooked. Here, by using multi-decadal gridded daily rainfall data over entire India, we show that the trend in spatial variability of mean monsoon rainfall is decreasing as exactly opposite to that of extremes. The spatial variability of extremes is attributed to the spatial variability of the convective rainfall component. Contrarily, the decrease in spatial variability of the mean rainfall over India poses a pertinent research question on the applicability of large scale inter-basin water transfer by river inter-linking to address the spatial variability of available water in India. We found a significant decrease in the monsoon rainfall over major water surplus river basins in India. Hydrological simulations using a Variable Infiltration Capacity (VIC) model also revealed that the water yield in surplus river basins is decreasing but it is increasing in deficit basins. These findings contradict the traditional notion of dry areas becoming drier and wet areas becoming wetter in response to climate change in India. This result also calls for a re-evaluation of planning for river inter-linking to supply water from surplus to deficit river basins. Indian summer monsoon rainfall (ISMR) over India contributes approximately 80% of the annual precipitation during June-September (Jun–Sep) . India’s). The hydrologic simulations were performed with a Variable Infiltration Capacity (VIC) model [S1 Text). The model was validated with satellite-based observation from the European Space Agency-Climate Change Initiative (ESA-CCI) soil moisture data [The gridded daily rainfall data (mm/day) from the India Meteorological Department (IMD), for the years 1901–2004 at a resolution of 1°  were useS1 TextC) model  in energure data ,29. The The spatial variability of the mean and extreme of the ISMR exhibit opposing trends. In the present case, rainfall associated with a return period of 50 years  was consWe address the first point with hydrological simulations over entire India and by computing the water yield  sum of . The resTo reconfirm our conclusions, we conducted a trend analysis of the ISMR over water surplus and deficit river basins in India . The majTo investigate the systematic nature and consistency of the opposing trends in the spatial variability of the mean and extreme ISMRs, we selected five regions of equal grid-size from different agro-climatic zones  in the surplus (deficit) river basins strongly contradict the traditional notion of wet (dry) areas becoming wetter (drier) over India. Our conclusion corroborates a study conducted by Greve et al. , who repS1 FigThe spatial variability of the mean does not exhibit a trend pre-1950 (a) and a significant decrease post-1950 (b). The spatial variability of extremes does not exhibit a trend pre-1950 (c) and a significant increase post-1950 (d).(TIF)Click here for additional data file.S2 Fig(a) The spatial variability of the mean monsoonal rainfall (blue), with the black solid line indicating the fitted trend line, and (b) the spatial variability for rainfall extremes (blue) with the black line representing the linear trend. The respective Mann-Kendall trend and associated p values are individually presented for each panel.(TIF)Click here for additional data file.S3 Fig(a) Correlation between the simulated and observed soil moisture from 1979–2004. (b) Normalized Root Mean Square Error (nRMSE) for the same period.(TIF)Click here for additional data file.S4 FigTrends in temperature (a), ET (b) and soil moisture (c) over India during 1951–2004, respectively. (d) shows a scatter plot of ET and temperature over India. The values inset the figures represent magnitude of the correlation (R) and slope for the respective variables. All the values are significant at 10% significance level.(TIF)Click here for additional data file.S5 Fig(a) Ratio of convective to total precipitation obtained from TRMM for all of India. (b) Trend in the spatial variability of the Indian Summer Monsoon Rainfall  for the stratiform precipitation obtained from MERRA database over the Indian region (blue), where the black line indicates the fitted trend (linear) line. The Modified Mann-Kendall trend is insignificant at the 5% level. (c) is similar to (b) except for the trend in convective precipitation, which is significant at the 5% level. The spatial data obtained from TRMM and MERRA were re-gridded to IMD at a 1° resolution using a linearly interpolated technique.(TIF)Click here for additional data file.S6 Fig(TIF)Click here for additional data file.S7 Fig(a) The trend in the spatial variability of convective precipitation (blue) during 1951–2004 for ERA-20c reanalysis data, where the black line indicates the fitted trend (linear) line. The modified Mann-Kendall trend is significant at the 5% level. (b) is similar to (a) but shows stratiform precipitation, for which the trend is insignificant at the 5% level. Trends in convective precipitation (c) and stratiform precipitation (d) during 1961–2004 for JRA-55 reanalysis data. The modified Mann-Kendall trend is insignificant at the 5% level for both convective and stratiform precipitation. The spatial data obtained from ERA-20c and JRA-55 were regridded to a 1° resolution (same as the IMD data resolution) using a linearly interpolated technique.(TIF)Click here for additional data file.S8 Fig(a) Spatial correlation for the monsoonal mean and (b) spatial correlation for the seasonal maxima. (c) The trend in the spatial correlation of individual grid points over the given region estimated with a 30-year overlapping moving window for the monsoonal mean. (d) same as (c) but for seasonal maxima.(TIF)Click here for additional data file.S9 Fig(TIF)Click here for additional data file.S1 TextContains complete description of methods and also the Tables.(DOCX)Click here for additional data file.


The use of medication during pregnancy should be taken with caution, especially because of its implications for maternal and fetal health. The mycophenolate sodium (MFS) is used to avoid possible rejection of transplanted tissues and organs by inhibiting T and B lymphocyte proliferation.To evaluate the effects of maternal immunosuppression by MFS on physiological parameters in rats.The rats were divided into three groups: rats treated with water (CONT=10) rats orally treated with MFS (20mg/Kg) daily for 15 days until a positive diagnosis of pregnancy (MICO-1=10) and rats orally treated with MFS (20mg/Kg) daily for 15 days prior to and during 21 days of pregnancy (MICO-2=10). It was weekly evaluated body weight, blood glucose, and water and food intake (before and during pregnancy). Statistical significance was p <0.05.In the pre-pregnancy period, although there were no changes in body weight values, the continuous treatment with MFS decreased food and water consumption and also increased blood glucose (MICO-2). During pregnancy period, these rats presented a reduction of the body weight, maintaining a mild hyperglycemia level (about 170 mg/dL)The continued use of MFS during pregnancy can be considered toxic, damaging the maternal health, lead to mild hyperglycemia state plus some toxic data (low food and water intake). This study shows that MFS use is not recommended during pregnancy freely and should be replaced by another immunosuppressant.


One of the challenges facing us in India, translating recent discoveries of chronic disease associated SNPs into clinical domain for prevention, is the lack of knowledge about the frequency of the polymorphism in our population. Hence, using available HapMap data has become a norm. However, it is anticipated that population genomics in India could be different from the HapMap Caucasian population. Relative disease risk prediction based on relevant SNPs, both for personalized medicine and for population genetics, has little value without accurate information of population allele frequencies. We report allele frequency of 384 SNPs directly related to chronic disease risk and metabolic traits in the Indian population.We report the allele in a random sample of 146 individuals and compare them with the data reported in HapMap Caucasian population (n = 112). Genotyping was performed using Illumina golden gate genotyping assay following DNA extraction from saliva. Allele frequencies were determined by direct gene count method.GWAS studies confirmed 384 SNPs to be associated with disease risk (364) of Diabetes Type 1 and 2 (54 & 118 respectively), Coronary artery disease(71), myocardial infarction(9), cardiac failure(24), sudden cardiac arrest(38), atrial fibrillation(9), hypertension(18), obesity(10), metabolic syndrome(2) and stroke(11); or were associated with metabolic traits (20). The master table of their ‘rs’ id, chromosomes, location and association is presented. Of the 384 SNPs, 44 were not in H-W equilibrium and were omitted. HapMap data were not available for 13 SNPs. We are reporting their allele frequencyon the Indian population for the first time. Of the remaining 307 disease association SNPs, statistically significant difference (p<.05) from HapMap Caucasian population was observed in 53% of them (164 of 307) and the difference of >10% (considered major in population genetics) was found in 42% (130 of 307). Of the 20 metabolic association SNPs, 50% (10 of 20) had statistically significant difference and in all of them it was >10%.We are reporting the largest repository, documenting disease and related SNP and allele frequencies in Indian population. We have also highlighted clear differences with HapMap data and would caution against indiscriminate use of HapMap for bench-to-bedside application of genetic knowledge in our population.


In 2011, the University of Michigan’s Center of Excellence in Public Health Workforce Studies and the Association of Public Health Laboratories (APHL) assessed the workforce and program capacity in U.S. public health, environmental, and agricultural laboratories  of 105 laboratory directors participated. A laboratorian was defined as a person whose principal work was in a governmental public health, environmental, or agricultural laboratory; positions could be reported as one-quarter fractions of full-time equivalents. For each program area, the director was asked if they had adequate capacity to perform necessary services for that program area. Estimates were categorized as follows: full = 100% capacity to perform; almost full = 75%–99%; substantial = 50%–74%; partial = 25%–49%; minimal = 1%–24%; and none. Fifty-six (71%) of the laboratories self-identified as a public health (49), environmental (three), or agricultural (four) laboratory; 23 (29%) self-identified as some combination of these categories; and one did not specify laboratory type.In 2011, a total of 6,656 employees, of whom 5,555 (83%) were laboratorians in one of the eight job classifications identified, worked in the 80 responding laboratories; the remaining 894 employees (13%) were administrative support staff, and 207 (4%) were information technology staff . The disFor those laboratories indicating any capacity in a given program area , more than half reported either no, minimal, or only partial capacity to perform necessary activities in toxicology (65%), agricultural chemistry (80%), agricultural microbiology (80%), clinical chemistry/hematology (68%), and education and training (55%). Conversely, more than 75% of laboratories reported substantial to full capacity in emergency preparedness and response (89%), safety and/or security (91%), bacteriology (91%), administration/operations (86%), molecular biology (92%), quality assurance (83%), serology/immunology (85%), and regulation and inspection (80%); however, fewer than half reported substantial to full capacity in agricultural chemistry (20%), agricultural microbiology (20%), clinical chemistry/hematology (32%), toxicology (35%), and education and training (45%) . SeveralMore than half of laboratories (42 [53%]) anticipated that up to 15% of their workers would retire, resign, or be released within 5 years, whereas 27 (34%) laboratories predicted a loss of 16%–25%, 10 (13%) predicted a loss of 26%–50%, and one anticipated losing more than 75% within 5 years. The lack of opportunities for promotion and lack of a career path for advancement were the two most common barriers to recruitment; both were reported by 76% of responding laboratories. Other major barriers to recruitment were inadequate salary scale (59 [74%]), hiring policies/procedures (54 [68%]), and complexity of the administrative bureaucracy (49 [61%]). Lack of promotion opportunities and career path for advancement were reported as obstacles to worker retention by 66 (83%) and 64 (80%) of laboratories, respectively, as was inadequate salary scale by 58 (73%) of laboratories.The public health, environmental, and agricultural laboratory workforce is a vital component of the nation’s public health infrastructure. Laboratory capacity is essential for protection against health hazards and provision of essential community services . The 201The lack of many laboratories’ ability to provide training to their staff is a concern because access to continuing education is essential to ensuring a well-trained public health workforce. This might be particularly true for laboratorians because only one quarter of laboratorians have a graduate or professional degree. Laboratory directors and public health, environmental, and agricultural laboratory workers reported lack of opportunities for promotion and a clear career path to advancement as the most common barriers to worker recruitment and retention , which mThe assessment of laboratories’ program area capacity should be based on the Laboratory System Improvement Plan (LSIP) standards, which were developed by APHL and CDC to assess laboratory performance ,8. HowevThe findings of this report are subject to at least three limitations. First, only three quarters of laboratory directors completed the survey; nonresponders might have differed systematically from responders and yielded dissimilar results if they had participated. Second, the questions used to assess program area capacity in the laboratory were subjective, and their interpretation might have varied by respondent. Finally, some subjective questions have objective correlates, such as assessment of equipment quality.What is already known on this topic?The public health, environmental, and agricultural laboratory workforce is a vital component of the nation’s public health infrastructure. Well-trained laboratorians are essential to providing protection against newly emergent diseases and other health hazards through diagnostic testing; reporting and surveillance; chemical, toxicologic, and environmental analysis; emergency preparedness; and provision of other vital services for the community.What is added by this report?Data from a 2011 National Laboratory Capacity Assessment indicate that national public health laboratory capacity needs to improve in several areas to achieve optimal testing and response capacity. Laboratory workers need better access to training and educational opportunities to ensure a well- qualified laboratory workforce.What are the implications for public health practice?Agencies at the local, state, and federal level should collaborate to improve laboratory capacity, including worker training and education, and encourage the development of a greater number and type of available laboratory degree programs.Healthy People 2020 public health infrastructure objective no. 11 (PHI-11) aims to increase the proportion of tribal and state public health agencies that provide or ensure comprehensive laboratory services to support essential public health services (The services . The Nat


Juvenile Dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in childhood, a systemic vasculopathy that usually affects skin and skeletal muscle but also can affect gastrointestinal tract and other organs. Diagnosis is based on Bohan and Peter's criteria and the goals of treatment include control of skin and muscle symptoms and prevention of disease complications. Stepwise aggressive treatment decreases JDM activity and improves long-term outcome.Muscle involvement in JDM can be assessed by electromyography (EMG), magnetic resonance imaging (MRI) and/or muscle biopsy.Muscle biopsy assesses the presence of lymphocytic inflammatory infiltrate, perifascicular atrophy, muscle fibers necrosis and it allows studying the overexpression of major histocompatibility complex (MHC) class I in the sarcolemma and sarcoplasm of the muscle cell. In healthy muscles, there is no MHC class I expression but in inflammatory myopathies there is a distinctive and generalized overexpression, not limited to the affected areas, it appears before the inflammatory infiltrate occurs and it is not modified by immunosuppressive treatment.To assess MHC I overexpression on muscle biopsy of our patients with JDM.Descriptive retrospective review of our JDM patients with muscle biopsy at diagnosis between January 2000 and December 2011. In all cases, muscle biopsy techniques were performed with hematoxylin-eosin, trichrome, oxidative enzymes , neonatal myosin and MHC class I.12 patients were included, 8 of them were girls (66%). All children had cutaneous and muscular clinical features at diagnosis. All MRI were pathological before treatment. EMG was performed in 9 patients, being altered in 8 of them (88%). Childhood Myositis Assessment Scale (CMAS) was done in 6 children with a median score of 30.5/52 (range 12-50/52). We found pathological muscle biopsy in 8 children (66%). Mild endomisial inflammation was found in 5 (41%) patients and moderate inflammation in 4 (33%). No vasculitis was found, but 7 (58%) patients had necrotic muscle fibers in biopsy. Immunohistochemical staining for MHC class I was positive in all cases, even in those children with normal muscle biopsy.MHC class I overexpression is present in muscle biopsy of all our patients with suspected JDM, even those with negative EMG or normal CMAS score. Although it is an invasive technique, muscle biopsy including MHC class I staining should be performed in all patients with suspected JDM in order to achieve more accurate diagnostic and establish an early and aggressive treatment.None declared.


Many patients die and majority of those who survive remain in a vegetative state2. There is paucity of data on the clinical characteristics and outcome of patients with status myoclonus treated with hypothermia from resource-limited centres in South Asia.Generalized status myoclonus following out of hospital cardiac arrest (OHCA) has been associated with poor prognosisTo study the clinical characteristics and outcome of patients with status myoclonus following out of hospital cardiac arrest and treated with hypothermia.Retrospective chart review of patients surviving > 24 hours following OHCA in an urban community hospital in South India, between January 2006 and December 2012. All patients received therapeutic hypothermia (32-34°C) for 24 hours. Data on the clinical characteristics of patients developing status myoclonus  and their outcome  were studied in detail. Based on the cerebral performance category (CPC) score at hospital discharge, the neurological outcome of patients was classified into favorable  and unfavorable .Out of the 124 patients surviving > 24 hours, 52 (42%) developed status myoclonus. Baseline and general characteristics were similar in patients with and without status myoclonus (Table Status myoclonus following out of hospital cardiac arrest was associated with unfavorable outcome. Majority of deaths in patients who developed status myoclonus was secondary to WLST, which may indicate self-fulfilling prophecy.


Data have been retrieved from several databases mentioned in details in the text. Determination and analysis of the structural and functional impact of TAFI and its expression could help elucidate the contribution of the TAFI pathway to acquired hemostatic dysfunction and will form the basis of potential therapeutic strategies to manipulate this pathway. An inhibition of TAFI (e.g. by FXI inhibitors) will offer the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders including cancer.The data in this paper is related to the research article entitled “Thrombin-activatable fibrinolysis inhibitor Thr325Ile polymorphism and plasma level in breast cancer: A pilot study”   Specifications TableValue of the data•in silico analysis of the structural and functional characterization of TAFI and its expression.This data provides a comprehensive •The data are useful for understanding the effect of TAFI variants on its structure and function.•This data may provide insight for determining the role of future drug treatment to inhibit TAFI function especially in cancer cases.11.1Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) represents the molecular link between the coagulation and fibrinolytic pathways TAFI activity is generated during the blood clotting process via binding to thrombin, thrombin–thrombomodulin complex, or plasmin, which in turn cleave TAFI protein at Arg114  into N-terminal activation peptide and catalytic domains, leading to exposure of the active site cleft of activated TAFI (TAFIa) 1.2The plasma concentration of TAFI appears to be under the control of genetic factors and non-genetic factors 1.3in silico analysis predicted these two coding SNPs to be functionally neutral using polymorphism phenotyping (PolyPhen) version 2 and MutPred web-based programs According to several databases, TAFI gene contains multiple variants; all are rare with minor allele frequencies (MAF) of less than 0.001 except two common natural variants rs3742264 and rs1926447 at positions 46073959 and 46055809 with MAF of 0.31 (T) and 0.22 (A), respectively,


G protein coupled receptors (GPCR) comprise a large family of transmembrane proteins involved in the regulation of signal transduction through the cell membrane in response to various extracellular stimuli. GPCR have become important targets of many drugs for treatments of very different diseases. During the last decade several fluorescence-based methods have been implemented for the characterization of signal transduction via GPCRs, starting from ligand binding and including several steps leading up to a response on the level of gene regulation. We have proposed the fluorescence anisotropy (FA) and fluorescence intensity (FI) assay to investigate fluorescent ligand binding properties to different GPCRs . The implementations of budded baculoviruses that display G protein-coupled receptors on their surfaces have significantly increased sensitivity and applicability of these assays . The developed novel assay systems opened new possibilities for real-time monitoring of ligand binding to their receptors for understanding their particular kinetic properties. These assays are also compatible for homogenous HTS suitable fo ligand screening. There has been implemented assay systems for receptors of peptides like melanocortin (MC4R) and neuropeptide Y (NPY1R) as well as for receptors of monoamines like dopamine (D1DAR) and serotonin (5-HT1AR).


The shoulder joint is the foundation for excellent upper extremity function. It contributes to stability and basic movements like rotation and elevation of the arm. Shoulder fusion should not be accepted even for total palsy, and nerve repair should be recommended as long as an available donor nerve exists.In planning the reconstructive procedure for shoulder function, accurate biomechanical analysis of individual glenohumeral (GH) and scapulothoracic (ST) joint is imperative, especially concerning serratus anterior muscle (SA) function.Priority of nerve repair and selection of donor nerve for shoulder function are the most important key points especially in C5~7, C5~8 and total palsy depending on accompanying reconstruction of elbow and finger function including conventional nerve transfer (NT) and free muscle transfer.Many previous articles of shoulder reconstruction with nerve repair following brachial plexus injuries were concluded from global shoulder motion that combine GH and ST motion, and emphasized only suprascapular nerve (SSN) repair. I emphasized SSN and long thoracic nerve (LTN) repair except in C56 palsy. The axillary nerve (Ax) can be ignored because simple AX palsy does not result in serious paralysis of shoulder function.Postoperative range of shoulder motions following SSN repair, in decreasing order according to individual donor nerve was; phrenic never (PN), spinal accessory nerve (SAN), C5 root and contralateral C7 (CC7 ) root. For LTN repair; the decreasing order of post operative range of shoulder joint movements were intercostal nerve (ICN), PN, SAN, C5 root and CC7 root. PN to SSN and ICN to LTN transfer achieved the most satisfactory outcome in total palsy; however, other combinations of nerve repair and AX repair did not provide significantly better shoulder motion.Dynamic shoulder XP is useful to differentiate between GH and ST motion for pre- and postoperative evaluation.I will introduce our techniques of the representative nerve repairs for shoulder reconstruction.


Wall shear stress (WSS) may be associated with the onset and development of aortopathy in the presence of bicuspid aortic valve (BAV) . The use of 'aortic atlases' of 3D WSS vectors allows for systematic analysis of WSS differences between large patient cohorts. In this study, a comparison is performed between WSS atlases of BAV patients, BAV patients with aortic dilation, patients with BAV stenosis, and healthy controls with tricuspid valves. The aim is to test the hypothesis that WSS atlases can identify regions of significantly altered WSS that are associated with different expression of BAV and aortopathy.Prospectively ECG and respiratory gated 4D flow MRI was performed in 10 healthy controls, 10 BAV patients, 10 BAV patients with aortic dilation (as defined by aorta diameter > 4 cm), and 10 patients with BAV stenosis (table Figure WSS atlases demonstrate the ability to regionally detect that all BAV patients exhibit significantly elevated WSS compared to healthy volunteers with tricuspid valves.NIH NHLBI grant R01HL115828; American Heart Association Scientist Development Grant 13SDG14360004.


Staphylococcus aureus (MRSA) clonal complex 398 septicemia in persons who had no contact with livestock. Whole-genome sequencing of the isolated MRSA strains strongly suggest that both were of animal origin and that the patients had been infected through 2 independent person-to-person transmission chains.We describe 2 fatal cases of methicillin-resistant  Staphylococcus aureus (MRSA) clonal complex (CC) 398 is associated with livestock and can spread to humans who have contact with animals . On the basis of these data, a phylogenetic tree was constructed from single-nucleotide polymorphism differences in genome sequences of isolates from the 4 patients and from the isolates obtained during the previous study by using the S0385 complete genome sequence (GenBank accession no. AM990992.1) as reference (tet(M) and czrC determinants (similar to most MRSA strains from clade IIa) and lacked the ɸSa3 phage   and the nursing home . Transmission of MRSA CC398 in hospitals and institutions has been reported elsewhere, which underscores its potential to spread through person-to-person contact (In conclusion, the organism implicated in these 2 fatal cases was by all accounts spread from person to person. These findings suggest that this clonal complex can be of high pathogenicity and is readily transmissible among humans.


Investigators from 4 pediatric hospitals in Canada analyzed the clinical presentation and electrophysiological data of 12 children with hereditary neuropathy with liability to pressure palsies (HNPP), caused by PMP22 gene deletion. Investigators from 4 pediatric hospitals in Canada analyzed the clinical presentation and electrophysiological data of 12 children with hereditary neuropathy with liability to pressure palsies (HNPP), caused by PMP22 gene deletion. Peroneal palsy was the most common presentation (42%) followed by brachial plexus palsy in 25% of their cases. Complete nerve conduction studies were available in 10/12 cases and it demonstrated 3 major patterns: multifocal demyelination at areas of nerve entrapment without generalized demyelinating polyneuropathy (20%), isolated generalized sensorimotor polyneuropathy (20%), combined focal demyelination at the area of entrapment and demyelinating polyneuropathy (60%). All patients had electrophysiological evidence of unilateral or bilateral carpal tunnel syndrome, although it was not always symptomatic. Electrophysiological findings are useful in diagnosis of HNPP, especially in children with heterogeneous clinical presentation. [COMMENTARY. HNPP is the third most common type of hereditary motor and sensory neuropathy . The typ


Estonian concentrated HIV epidemic started in August 2000 when rare HIV-1 CRF06_cpx was introduced into the population of intravenous drug users (IDUs). The majority of these HIV-positive subjects are likely co-infected with HCV but the prevalence of HCV and its genotypes during HIV concentrated epidemic in Estonia is largely unknown. The Estonian HIV database collects clinical and laboratory data (including HCV) of HIV-positive patients on medical care. Of 4500 patients on medical care 3500 are entered into Estonian HIV database .Aim: to describe the prevalence of HCV infection and the distribution of the HCV genotypes among HIV-positive subjects infected during HIV concentrated epidemic in Estonia.nd of January 2014 and it comprised subjects diagnosed HIV-positive from 2000.Data for present analyses was extracted from Estonian HIV database on 2In total 2,420 of 3,476 (70%) HIV-positive subjects were HCV antibody positive and 1,184 (64%) were HCV RNA positive. More than half of HCV-positives were men (66%) and the median age was 32 years (inter quartile range 30-36 y). The prevalence of HCV was higher in subjects verified to be HIV-positive between 2002 and 2010 as compared to between 2011 and 2013 . The prevalence of HCV-positivity was equally high in subjects reporting the use of intravenous drugs (88%), the use of other narcotics but intravenous drugs (69%) and persons who have not reported the use of illegal drugs (71%). In total 640 subjects had HCV genotype data available. The dominating genotypes were Ib (53%) and IIIa (36%), however, in recent years the prevalence of genotype Ia is raising (from 2.6% in 2005 to 25% in 2013). The distribution of HCV genotypes between different IDUs and non-IDUs was similar. Altogether 5% of HCV RNA positive subjects  received HCV treatment and all except one admitted the drug usage. Of 59 subjects 48 (81%) received both HCV and HIV therapy.Decreased prevalence of HCV-positive subjects among HIV-positives may suggest a lowered HIV transmission through intravenous route during the last years. The high prevalence of HCV in persons who did not report the use of illegal drugs might indicate under-reported drug usage in this population.


Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of the endothelial cell-derived tumor Kaposi's sarcoma and of the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman's disease. The life cycle of KSHV includes a latent and a lytic/productive phase that both contribute to tumorigenic activity. Major threats for infected tumor cells are attacks of the immune system and the induction of endogeneous cell death programs in response to the virus infection. KSHV opposes these threats for example by hiding from the immune attack by entering the latent infection phase where only few genes are expressed and replication is absent or in the productive phase by the downregulation of major histocompatibility complex class I on the surface of infected cells. Moreover, KSHV uses several different strategies to counteract endogenous cell death programs such as apoptosis and necroptosis.KSHV encodes more than 87 ORFs (open reading frames) and numerous ribosomal-loaded not previously annotated RNAs . ORF actIn another RTCM-based study the effects of all KSHV-encoded genes on the inhibition of p53 were investigated. The tumor suppressor p53 is a major regulatory molecule of apoptosis and cell cycle progression. Three structural proteins namely ORF22 (envelope glycoprotein gH), ORF25 (major capsid protein) and ORF64 (tegument protein) were identified as potent inhibitors of p53 signaling [Finally, viral DNA establishes a pathogen associated molecular pattern (PAMP) that can trigger the host innate immune responses by stimulating production of type I interferons (IFNs). This leads to repression of viral replication and elimination of virus infected cells by apoptosis. Systematic analyses of all KSHV-encoded genes identified the tegument protein ORF52 as a potent inhibitor of this pathway . ORF52 aAltogether, the transfection studies summarized here indicate that KSHV encodes a large repertoire of genes regulating survival of the infected cell in all stages of the viral life cycle Figure . In the


The kidneys are known as a target of hepatitis viruses. The renal impairment associated with hepatitis B virus (HBV) could be represented by lesions of glomeruli, or by injury of the renal tubules. Membranous nephropathy is the most common form of glomerulonephritis associated with HBV infection. We aimed to develop a prospective study that evaluated the relation between serum levels of 8-hydroxy-2-deoxiguanosine (8OHdG) and total antioxidant status (TAS) in patients with membranous glomerulopathy associated with HBV infection.The study included a group of 18 patients with chronic infection with HBV and membranous nephropathy with nephrotic syndrome, without renal failure (eGFR >60mL/min/1.73sqm), and a group of 20 patients with chronic infection with HBV without membranous glomerulonephritis. The patients did not receive any treatment for the mentioned diseases before the inclusion in the study. The groups were similar for demographic and nutritional status characteristics. The assessment of 8OHdG, a metabolite of oxidative damage of DNA, was made by ELISA method. TAS was determined by spectrophotometric method.In patients with chronic HBV infection and membranous nephropathy, 8OHdG (ng/mL serum) had higher levels than in patients with chronic HBV infection without renal disease . Serum levels of TAS (mmol/L serum) were significantly lower in patients with membranous glomerulopathy compared with those without nephropathy . A statistically strong negative correlation was determined between 8OHdG and TAS in patients with glomerulopathy associated with HBV infection.The negative association between serum levels of 8OHdG and TAS in patients with membranous nephropathy induced by HBV infection suggests an important role of oxidative stress in the development of renal diseases. The adjustment of imbalance between levels of reactive oxygen/nitrogen species and those of antioxidants in the human body could represent a goal for a better management of renal diseases.