Epidemiology of hepatitis C virus among hemodialysis patients in the Middle East and North Africa: systematic syntheses, meta-analyses, and meta-regressions.

We aimed to investigate hepatitis C virus (HCV) epidemiology among hemodialysis (HD) patients in the Middle East and North Africa (MENA). Our data source was an HCV biological measures database populated through systematic literature searches. Descriptive epidemiologic syntheses, effects meta-analyses and meta-regressions, and genotype analyses were conducted. We analyzed 289 studies, including 106 463 HD patients. HCV incidence ranged between 0 and 100% as seroconversion risk, and between 0 and 14·7 per 1000 person-years as incidence rate. The regional pooled mean estimate was 29·2% (95% CI: 25·6-32·8%) for HCV antibody positive prevalence and 63·0% (95% CI: 55·4-70·3%) for the viremic rate. Region within MENA, country income group, and year of data collection were associated with HCV prevalence; year of data collection adjusted odds ratio was 0·92 (95% CI: 0·90-0·95). Genotype diversity varied across countries with four genotypes documented regionally: genotype 1 (39·3%), genotype 2 (5·7%), genotype 3 (29·6%), and genotype 4 (25·4%). Our findings showed that one-third of HD patients are HCV antibody positive and one-fifth are chronic carriers and can transmit the infection. However, HCV prevalence is declining. In context of growing HD patient population and increasing HCV treatment availability, it is critical to improve standards of infection control in dialysis and expand treatment coverage

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

DNA repair: the culprit for tumor-initiating cell survival?

The existence of “tumor-initiating cells” (TICs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has led to an abundance of evidence supporting their existence. TICs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately leading to metastasis and patient demise. This review summarizes DNA repair mechanism(s) and their role in the maintenance and regulation of stem cells. There is evidence supporting the hypothesis that TICs, similar to embryonic stem (ES) cells and hematopoietic stem cells (HSCs), display an increase in their ability to survive genotoxic stress and injury. Mechanistically, the ability of ES cells, HSCs and TICs to survive under stressful conditions can be attributed to an increase in the efficiency at which these cells undergo DNA repair. Furthermore, the data presented in this review summarize the results found by our lab and others demonstrating that TICs have an increase in their genomic stability, which can allow for TIC survival under conditions such as anticancer treatments, while the bulk population of tumor cells dies. We believe that these data will greatly impact the development and design of future therapies being engineered to target and eradicate this highly aggressive cancer cell population

Epidemiology of Chlamydia trachomatis in the Middle East and north Africa: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: The epidemiology of Chlamydia trachomatis in the Middle East and north Africa is poorly understood. We aimed to provide a comprehensive epidemiological assessment of C trachomatis infection in the Middle East and north Africa. METHODS: We did a systematic review of C trachomatis infection as well as a meta-analysis and meta-regression of C trachomatis prevalence. We searched PubMed and Embase, as well as regional and national databases up to March 13, 2019, using broad search terms with no language or year restrictions. Any document or report including biological measures for C trachomatis prevalence or incidence was eligible for inclusion. We extracted all measures of current (genital or rectal), recent, and ever infection with C trachomatis. We estimated pooled average prevalence in different populations using random-effects meta-analysis. Factors associated with prevalence and sources of between-study heterogeneity were determined using meta-regression. FINDINGS: We identified a total of 1531 citations, of which 255 reports contributed to 552 C trachomatis prevalence measures from 20 countries. No incidence measures were identified. Pooled prevalence of current genital infection was 3·0% (95% CI 2·3-3·8) in general populations, 2·8% (1·0-5·2) in intermediate-risk populations, 13·2% (7·2-20·7) in female sex workers, 11·3% (9·0-13·7) in infertility clinic attendees, 12·4% (7·9-17·7) in women with miscarriage, 12·4% (9·4-15·7) in symptomatic women, and 17·4% (12·5-22·8) in symptomatic men. Pooled prevalence of current rectal infection was 7·7% (4·2-12·0) in men who have sex with men. Substantial between-study heterogeneity was found. Multivariable meta-regression explained 29·0% of variation. Population type was most strongly associated with prevalence. Additional associations were found with assay type, sample size, country, and sex, but not with sampling methodology or response rate (about 90% of studies used convenience sampling and >75% had unclear response rate). There was no evidence for temporal variation in prevalence between 1982 and 2018. INTERPRETATION: C trachomatis prevalence in the Middle East and north Africa is similar to other regions, but higher than expected given its sexually conservative norms. High prevalence in infertility clinic attendees and in women with miscarriage suggests a potential role for C trachomatis in poor reproductive health outcomes in this region. FUNDING: National Priorities Research Program from the Qatar National Research Fund (a member of Qatar Foundation)

Heparan Sulfate Proteoglycans Mediate Interstitial Flow Mechanotransduction Regulating MMP-13 Expression and Cell Motility via FAK-ERK in 3D Collagen

Interstitial flow directly affects cells that reside in tissues and regulates tissue physiology and pathology by modulating important cellular processes including proliferation, differentiation, and migration. However, the structures that cells utilize to sense interstitial flow in a 3-dimensional (3D) environment have not yet been elucidated. Previously, we have shown that interstitial flow upregulates matrix metalloproteinase (MMP) expression in rat vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts via activation of an ERK1/2-c-Jun pathway, which in turn promotes cell migration in collagen. Herein, we focused on uncovering the flow-induced mechanotransduction mechanism in 3D.Cleavage of rat vascular SMC surface glycocalyx heparan sulfate (HS) chains from proteoglycan (PG) core proteins by heparinase or disruption of HS biosynthesis by silencing N-deacetylase/N-sulfotransferase 1 (NDST1) suppressed interstitial flow-induced ERK1/2 activation, interstitial collagenase (MMP-13) expression, and SMC motility in 3D collagen. Inhibition or knockdown of focal adhesion kinase (FAK) also attenuated or blocked flow-induced ERK1/2 activation, MMP-13 expression, and cell motility. Interstitial flow induced FAK phosphorylation at Tyr925, and this activation was blocked when heparan sulfate proteoglycans (HSPGs) were disrupted. These data suggest that HSPGs mediate interstitial flow-induced mechanotransduction through FAK-ERK. In addition, we show that integrins are crucial for mechanotransduction through HSPGs as they mediate cell spreading and maintain cytoskeletal rigidity.We propose a conceptual mechanotransduction model wherein cell surface glycocalyx HSPGs, in the presence of integrin-mediated cell-matrix adhesions and cytoskeleton organization, sense interstitial flow and activate the FAK-ERK signaling axis, leading to upregulation of MMP expression and cell motility in 3D. This is the first study to describe a flow-induced mechanotransduction mechanism via HSPG-mediated FAK activation in 3D. This study will be of interest in understanding the flow-related mechanobiology in vascular lesion formation, tissue morphogenesis, cancer cell metastasis, and stem cell differentiation in 3D, and also has implications in tissue engineering

Transcriptomic Signatures of Ash (Fraxinus spp.) Phloem

Ash (Fraxinus spp.) is a dominant tree species throughout urban and forested landscapes of North America (NA). The rapid invasion of NA by emerald ash borer (Agrilus planipennis), a wood-boring beetle endemic to Eastern Asia, has resulted in the death of millions of ash trees and threatens billions more. Larvae feed primarily on phloem tissue, which girdles and kills the tree. While NA ash species including black (F. nigra), green (F. pennsylvannica) and white (F. americana) are highly susceptible, the Asian species Manchurian ash (F. mandshurica) is resistant to A. planipennis perhaps due to their co-evolutionary history. Little is known about the molecular genetics of ash. Hence, we undertook a functional genomics approach to identify the repertoire of genes expressed in ash phloem.Using 454 pyrosequencing we obtained 58,673 high quality ash sequences from pooled phloem samples of green, white, black, blue and Manchurian ash. Intriguingly, 45% of the deduced proteins were not significantly similar to any sequences in the GenBank non-redundant database. KEGG analysis of the ash sequences revealed a high occurrence of defense related genes. Expression analysis of early regulators potentially involved in plant defense (i.e. transcription factors, calcium dependent protein kinases and a lipoxygenase 3) revealed higher mRNA levels in resistant ash compared to susceptible ash species. Lastly, we predicted a total of 1,272 single nucleotide polymorphisms and 980 microsatellite loci, among which seven microsatellite loci showed polymorphism between different ash species.The current transcriptomic data provide an invaluable resource for understanding the genetic make-up of ash phloem, the target tissue of A. planipennis. These data along with future functional studies could lead to the identification/characterization of defense genes involved in resistance of ash to A. planipennis, and in future ash breeding programs for marker development