Hepatitis C Virus Infection in Populations With Liver-Related Diseases in the Middle East and North Africa.

We investigated hepatitis C virus (HCV) epidemiology in populations with liver-related diseases (LRDs) in the Middle East and North Africa. The data source was standardized databases of HCV measures populated through systematic reviews. Random-effects meta-analyses and meta-regressions were performed, and genotype diversity was assessed. Analyses were based on 252 HCV antibody prevalence measures, eight viremic rate measures, and 30 genotype measures on 132,358 subjects. Pooled mean prevalence in LRD populations was 58.8% (95% confidence interval [CI], 51.5%-66.0%) in Egypt and 55.8% (95% CI, 49.1%-62.4%) in Pakistan; these values were higher than in other countries, which had a pooled prevalence of only 15.6% (95% CI, 12.4%-19.0%). Mean prevalence was highest in patients with hepatocellular carcinoma at 56.9% (95% CI, 50.2%-63.5%) and those with cirrhosis at 50.4% (95% CI, 40.8%-60.0%). Type of LRD population and country were the strongest predictors of prevalence, explaining 48.6% of the variation. No evidence for prevalence decline was found, but there was strong evidence for prevalence increase in Pakistan. A strong, positive association was identified between prevalence in the general population and that in LRD populations; the Pearson correlation coefficient ranged between 0.605 and 0.862. The pooled mean viremic rate was 75.5% (95% CI, 61.0%-87.6%). Genotype 4 was most common (44.2%), followed by genotype 3 (34.5%), genotype 1 (17.0%), genotype 2 (3.5%), genotype 6 (0.5%), and genotype 5 (0.3%). Conclusion: HCV appears to play a dominant role in liver diseases in Egypt and Pakistan and has a growing role in Pakistan. Testing and treatment of LRD populations are essential to reduce disease burden and transmission and to reach HCV elimination by 2030

Individual-level key associations and modes of exposure for hepatitis C virus infection in the Middle East and North Africa: a systematic synthesis.

PURPOSE: To identify, map, and synthesize the individual-level key associations and modes of exposure for hepatitis C virus (HCV) infection in the Middle East and North Africa (MENA), the most affected region by HCV. METHODS: Source of data was the MENA HCV Epidemiology Synthesis Project database, populated through systematic literature searches. Risk factors determined to be statistically significant after adjustment for confounders were extracted and categorized into key associations or modes of exposure. RESULTS: In total, 329 risk factors were identified from 109 articles in 14 of 24 MENA countries. Among key associations, age was most frequently reported (n = 39; 34.2%), followed by other infections/diseases (n = 20; 17.5%), and incarceration (n = 17; 14.9%). Among modes of exposure, health care-related exposures were most frequently reported (n = 127; 59.5%), followed by injecting drug use exposures (n = 45; 20.9%), community-related exposures (n = 34; 15.8%), and sexual-related exposures (n = 8; 3.7%). Blood transfusion, hemodialysis, surgical and other medical procedures, dental work, and medical injections were identified as key health care-related exposures. CONCLUSIONS: Health care appears to be the primary driver of prevalent (and possibly incident) infections in MENA, followed by injecting drug use. HCV screening should target the identified modes of exposure. Commitment to prevention should be an integral component of HCV response to achieve HCV elimination by 2030, with focus on strengthening infection control in health care facilities, improving injection safety and blood screening, and expanding harm reduction services for people who inject drugs

System-Wide Immunohistochemical Analysis of Protein Co-Localization

Background: The analysis of co-localized protein expression in a tissue section is often conducted with immunofluorescence histochemical staining which is typically visualized in localized regions. On the other hand, chromogenic immunohistochemical staining, in general, is not suitable for the detection of protein co-localization. Here, we developed a new protocol, based on chromogenic immunohistochemical stain, for system-wide detection of protein co-localization and differential expression. Methodology/Principal Findings: In combination with a removable chromogenic stain, an efficient antibody stripping method was developed to enable sequential immunostaining with different primary antibodies regardless of antibody’s host species. Sections were scanned after each staining, and the images were superimposed together for the detection of protein co-localization and differential expression. As a proof of principle, differential expression and co-localization of glutamic acid decarboxylase67 (GAD67) and parvalbumin proteins was examined in mouse cortex. Conclusions/Significance: All parvalbumin-containing neurons express GAD67 protein, and GAD67-positive neurons that do not express parvalbumin were readily visualized from thousands of other neurons across mouse cortex. The method provided a global view of protein co-localization as well as differential expression across an entire tissue section. Repeate

Hospital admission and risk assessment associated to exposure of fungal bioaerosols at a municipal landfill using statistical models

The object of this research to determine the statistical relationship and degree of association between variables: hospital admission days and diagnostic (disease) potentially associated to fungal bioaerosols exposure. Admissions included acute respiratory infections, atopic dermatitis, pharyngitis and otitis. Statistical analysis was done using Statgraphics Centurion XVI software. In addition, was estimated the occupational exposure to fungal aerosols in stages of a landfill using BIOGAVAL method and represented by Golden Surfer XVI program. Biological risk assessment with sentinel microorganism A. fumigatus and Penicillium sp, indicated that occupational exposure to fungal aerosols is Biological action level. Preventive measures should be taken to reduce the risk of acquiring acute respiratory infections, dermatitis or other skin infections

Key associations for hepatitis C virus genotypes in the Middle East and North Africa.

This study aimed to investigate the epidemiology of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA) through an analytical and quantitative meta-regression methodology. For the most common genotypes 1, 3, and 4, country/subregion explained more than 77% of the variation in the distribution of each genotype. Genotype 1 was common across MENA, and was more present in high-risk clinical populations than in the general population. Genotype 3 was much more present in Afghanistan, Iran, and Pakistan than the rest of countries, and was associated with transmission through injecting drug use. Genotype 4 was broadly disseminated in Egypt in all populations, with overall limited presence elsewhere. While genotype 2 was more present in high-risk clinical populations and people who inject drugs, most of the variation in its distribution remained unexplained. Genotypes 5, 6, and 7 had low or no presence in MENA, limiting the epidemiological inferences that could be drawn. To sum up, geography is the principal determinant of HCV genotype distribution. Genotype 1 is associated with transmission through high-risk clinical procedures, while genotype 3 is associated with injecting drug use. These findings demonstrate the power of such analytical approach, which if extended to other regions and globally, can yield relevant epidemiological inferences

Hepatitis C virus genotypes in the Middle East and North Africa: Distribution, diversity, and patterns.

Our objective was to characterize the distribution, diversity and patterns of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA). Source of data was a database of HCV genotype studies in MENA populated using a series of systematic literature searches. Pooled mean proportions were estimated for each genotype and by country using DerSimonian-Laird random-effects meta-analyses. Genotype diversity within countries was assessed using Shannon Diversity Index. Number of chronic infections by genotype and country was calculated using the pooled proportions and country-specific numbers of chronic infection. Analyses were conducted on 338 genotype studies including 82 257 genotyped individuals. Genotype 1 was dominant (≥50%) in Algeria, Iran, Morocco, Oman, Tunisia, and UAE, and was overall ubiquitous across the region. Genotype 2 was common (10-50%) in Algeria, Bahrain, Libya, and Morocco. Genotype 3 was dominant in Afghanistan and Pakistan. Genotype 4 was dominant in Egypt, Iraq, Jordan, Palestine, Qatar, Saudi Arabia, and Syria. Genotypes 5, 6, and 7 had limited or no presence across countries. Genotype diversity varied immensely throughout MENA. Weighted by population size, MENA's chronic infections were highest among genotype 3, followed by genotype 4, genotype 1, genotype 2, genotype 5, and genotype 6. Despite ubiquitous presence of genotype 1, the vast majority of chronic infections were of genotypes 3 or 4, because of the sizable epidemics in Pakistan and Egypt. Three sub-regional patterns were identified: genotype 3 pattern centered in Pakistan, genotype 4 pattern centered in Egypt, and genotype 1 pattern ubiquitous in most MENA countries

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts

BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations

Hepatitis C virus viremic rate in the Middle East and North Africa: Systematic synthesis, meta-analyses, and meta-regressions.

OBJECTIVES: To estimate hepatitis C virus (HCV) viremic rate, defined as the proportion of HCV chronically infected individuals out of all ever infected individuals, in the Middle East and North Africa (MENA). METHODS: Sources of data were systematically-gathered and standardized databases of the MENA HCV Epidemiology Synthesis Project. Meta-analyses were conducted using DerSimonian-Laird random-effects models to determine pooled HCV viremic rate by risk population or subpopulation, country/subregion, sex, and study sampling method. Random-effects meta-regressions were conducted to identify predictors of higher viremic rate. RESULTS: Analyses were conducted on 178 measures for HCV viremic rate among 19,593 HCV antibody positive individuals. In the MENA region, the overall pooled mean viremic rate was 67.6% (95% CI: 64.9-70.3%). Across risk populations, the pooled mean rate ranged between 57.4% (95% CI: 49.4-65.2%) in people who inject drugs, and 75.5% (95% CI: 61.0-87.6%) in populations with liver-related conditions. Across countries/subregions, the pooled mean rate ranged between 62.1% (95% CI: 50.0-72.7%) and 70.4% (95% CI: 65.5-75.1%). Similar pooled estimates were further observed by risk subpopulation, sex, and sampling method. None of the hypothesized population-level predictors of higher viremic rate were statistically significant. CONCLUSIONS: Two-thirds of HCV antibody positive individuals in MENA are chronically infected. Though there is extensive variation in study-specific measures of HCV viremic rate, pooled mean estimates are similar regardless of risk population or subpopulation, country/subregion, HCV antibody prevalence in the background population, or sex. HCV viremic rate is a useful indicator to track the progress in (and coverage of) HCV treatment programs towards the set target of HCV elimination by 2030

Calpain Cleavage of Brain Glutamic Acid Decarboxylase 65 Is Pathological and Impairs GABA Neurotransmission

Previously, we have shown that the GABA synthesizing enzyme, L-glutamic acid decarboxylase 65 (GAD65) is cleaved to form its truncated form (tGAD65) which is 2–3 times more active than the full length form (fGAD65). The enzyme responsible for cleavage was later identified as calpain. Calpain is known to cleave its substrates either under a transient physiological stimulus or upon a sustained pathological insult. However, the precise role of calpain cleavage of fGAD65 is poorly understood. In this communication, we examined the cleavage of fGAD65 under diverse pathological conditions including rats under ischemia/reperfusion insult as well as rat brain synaptosomes and primary neuronal cultures subjected to excessive stimulation with high concentration of KCl. We have shown that the formation of tGAD65 progressively increases with increasing stimulus concentration both in rat brain synaptosomes and primary rat embryo cultures. More importantly, direct cleavage of synaptic vesicle - associated fGAD65 by calpain was demonstrated and the resulting tGAD65 bearing the active site of the enzyme was detached from the synaptic vesicles. Vesicular GABA transport of the newly synthesized GABA was found to be reduced in calpain treated SVs. Furthermore, we also observed that the levels of tGAD65 in the focal cerebral ischemic rat brain tissue increased corresponding to the elevation of local glutamate as indicated by microdialysis. Moreover, the levels of tGAD65 was also proportional to the degree of cell death when the primary neuronal cultures were exposed to high KCl. Based on these observations, we conclude that calpain-mediated cleavage of fGAD65 is pathological, presumably due to decrease in the activity of synaptic vesicle - associated fGAD65 resulting in a decrease in the GABA synthesis - packaging coupling process leading to reduced GABA neurotransmission