Role of Platelet Activating Factor as a Mediator of Inflammatory Diseases and Preterm Delivery.

Nearly 70% of preterm deliveries occur spontaneously, and the clinical pathways involved include preterm labor and preterm premature rupture of membranes. Prediction of preterm delivery is considered crucial due to the significant effects of preterm birth on health and the economy at both the personal and community levels. Although similar inflammatory processes occur in both term and preterm delivery, the premature activation of these processes or exaggerated inflammatory response triggered by infection or sterile factors leads to preterm delivery. Platelet activating factor (PAF) is a phosphoglycerylether lipid mediator of inflammation that is implicated in infections, cancers, and various chronic diseases and disorders including cardiovascular, renal, cerebrovascular, and central nervous system diseases. In gestational tissues, PAF mediates the inflammatory pathways that stimulate the effector mechanisms of labor, including myometrial contraction, cervical dilation, and fetal membrane rupture. Women with preterm labor and preterm premature rupture of membranes have increased levels of PAF in their amniotic fluid. In mice, the intrauterine or intraperitoneal administration of carbamyl PAF activates inflammation in gestational tissues, thereby eliciting preterm delivery. This review summarizes recent research on PAF as an important inflammatory mediator in preterm delivery and in other inflammatory disorders, highlighting its potential value for prediction, intervention, and prevention of these diseases.

Molecular Analysis and Ex Vivo Infectivity of Seronegative Occult Hepatitis C Virus: A Study in Single Haemodialysis Centre.

Background: In occult hepatitis C virus infection (OCI), hepatitis C virus ribonucleic acid (HCV RNA) is detectable in peripheral blood mononuclear cells (PBMCs) but is not evident in serum or plasma. Understanding of OCI in patients with seronegative anti-HCV antibodies is limited. Methods: In this study, six HCV isolates from haemodialysis (HD) patients with seronegative OCI were identified by molecular assays and phylogenetic analysis. The virus infectivity was assessed ex vivo using a primary naïve PBMC culture system. HCV isolates obtained from the PBMCs of 10 patients with chronic HCV infection (CCI) were characterised concurrently and used as positive controls in the cell culture. Results: Sequence analysis of the 5' untranslated region (UTR) and non-structural 5B (NS5B) region revealed that HCV genotype 3 was the most prevalent virus type in both the OCI and CCI groups. One of the occult HCV isolates was identified as a mixed type. The mean viral load (log10 RNA copies/106 cells) in the PBMC samples of the OCI group (M = 3.4, SD = 0.7) was lower than that of the CCI group (M = 4.6, SD = 1.7). Upon culture, de novo OCI-HCV replicates were detected in five out of six naïve PBMC cultures. Analysis of the replicates showed a single guanine addition in the domain III of 5'-UTR but the overall molecular structure was retained. Conclusion: Seronegative OCI is an active form of infection that replicates at a low level in PBMCs. Seronegative OCI may share the same route of transmission as CCI. The retained viral competency may have an implication for its persistence.

Sand Barriers around Latrine Pits Reduce Fecal Bacterial Leaching into Shallow Groundwater: A Randomized Controlled Trial in Coastal Bangladesh.

We evaluated the effectiveness of a sand barrier around latrine pits in reducing fecal indicator bacteria (FIB) leaching into shallow groundwater. We constructed 68 new offset single pit pour flush latrines in the Galachipa subdistrict of coastal Bangladesh. We randomly assigned 34 latrines to include a 50 cm thick sand barrier under and around the pit and 34 received no sand barrier. Four monitoring wells were constructed around each pit to collect water samples at baseline and subsequent nine follow-up visits over 24 months. Samples were tested using the IDEXX Colilert method to enumerate E. coli and thermotolerant coliforms most probable number (MPN). We determined the difference in mean log10MPN FIB counts/100 mL in monitoring well samples between latrines with and without a sand barrier using multilevel linear models and reported cluster robust standard error. The sand barrier latrine monitoring well samples had 0.38 mean log10MPN fewer E. coli (95% CI: 0.16, 0.59; p = 0.001) and 0.38 mean log10MPN fewer thermotolerant coliforms (95% CI: 0.14, 0.62; p = 0.002), compared to latrines without sand barriers, a reduction of 27% E. coli and 24% thermotolerant coliforms mean counts. A sand barrier can modestly reduce the risk presented by pit leaching.

A computational investigation of cis-gene regulation in evolution.

In biological processes involving gene networks, genes regulate other genes that determine the phenotypic traits. Gene regulation plays an important role in evolutionary dynamics. In a genetic algorithm, a trans-gene regulatory mechanism was shown to speed up adaptation and evolution. Here, we examine the effect of cis-gene regulation on an adaptive system. The model is haploid. A chromosome is partitioned into regulatory loci and structural loci. The regulatory genes regulate the expression and functioning of structural genes via the cis-elements in a probabilistic manner. In the simulation, the change in the allele frequency, the mean population fitness and the efficiency of phenotypic selection are monitored. Cis-gene regulation increases adaption and accelerates the evolutionary process in comparison with the case involving absence of gene regulation. Some special features of the simulation results are as follows. A low ratio of regulatory loci and structural loci gives higher adaptation for fixed total number of loci. Plasticity is advantageous beyond a threshold value. Adaptation is better for large number of total loci when the ratio of regulatory loci to structural loci is one. However, it reaches a saturation beyond which the increase in the total loci is not advantageous. Efficiency of the phenotypic selection is higher for larger value of the initial plasticity.

Prevalence and factors associated with pediatric HIV therapy failure in a tertiary hospital in Asmara, Eritrea: A 15-year retrospective cohort study.

INTRODUCTION: Treatment failure (TF) in HIV infected children is a major concern in resource-constrained settings in Sub-Saharan Africa (SSA). This study investigated the prevalence, incidence, and factors associated with first-line cART failure using the virologic (plasma viral load), immunologic and clinical criteria among HIV-infected children. METHODS: A retrospective cohort study of children (<18 years of age on treatment for a period of > 6 months) enrolled in the pediatric HIV/AIDs treatment program at Orotta National Pediatric Referral Hospital from January 2005 to December 2020 was conducted. Data were summarized using percentages, medians (± interquartile range (IQR)), or mean ± standard deviation (SD). Where appropriate, Pearson Chi-Squire (χ2) tests or Fishers exacts test, Kaplan-Meier (KM) estimates, and unadjusted and adjusted Cox-proportional hazard regression models were employed. RESULTS: Out of 724 children with at least 24 weeks' follow-up 279 experienced therapy failure (TF) making prevalence of 38.5% (95% CI 35-42.2) over a median follow-up of 72 months (IQR, 49-112 months), with a crude incidence of failure of 6.5 events per 100- person-years (95% CI 5.8-7.3). In the adjusted Cox proportional hazards model, independent factors of TF were suboptimal adherence (Adjusted Hazard Ratio (aHR) = 2.9, 95% CI 2.2-3.9, p < 0.001), cART backbone other than Zidovudine and Lamivudine (aHR = 1.6, 95% CI 1.1-2.2, p = 0.01), severe immunosuppression (aHR = 1.5, 95% CI 1-2.4, p = 0.04), wasting or weight for height z-score < -2 (aHR = 1.5, 95% CI 1.1-2.1, p = 0.02), late cART initiation calendar years (aHR = 1.15, 95% CI 1.1-1.3, p < 0.001), and older age at cART initiation (aHR = 1.01, 95% CI 1-1.02, p < 0.001). CONCLUSIONS: Seven in one hundred children on first-line cART are likely to develop TF every year. To address this problem, access to viral load tests, adherence support, integration nutritional care into the clinic, and research on factors associated with suboptimal adherence should be prioritized.

Attrition and associated factors among children living with HIV at a tertiary hospital in Eritrea: a retrospective cohort analysis.

BACKGROUND: Reducing attrition in paediatric HIV-positive patients using combined antiretroviral therapy (cART) programmes in sub-Saharan Africa is a challenge. This study explored the rates and predictors of attrition in children started on cART in Asmara, Eritrea. METHODS: This was a retrospective cohort study using data from all paediatric patients on cART between 2005 and 2020, conducted at the Orotta National Referral and Teaching Hospital. Kaplan-Meier estimates of the likelihood of attrition and multivariate Cox proportional hazards models were used to assess the factors associated with attrition. All p values were two sided and p<0.05 was considered statistically significant. RESULTS: The study enrolled 710 participants with 374 boys (52.7%) and 336 girls (47.3%). After 5364 person-years' (PY) follow-up, attrition occurred in 172 (24.2%) patients: 65 (9.2%) died and 107 (15.1%) were lost to follow-up (LTFU). The crude incidence rate of attrition was 3.2 events/100 PY, mortality rate was 2.7/100 PY and LTFU was 1.2/100 PY. The independent predictors of attrition included male sex (adjusted HR (AHR)=1.6, 95% CI: 1 to 2.4), residence outside Zoba Maekel (AHR=1.5, 95% CI: 1 to 2.3), later enrolment years (2010-2015: AHR=3.2, 95% CI: 1.9 to 5.3; >2015: AHR=6.1, 95% CI: 3 to 12.2), WHO body mass index-for-age z-score <-2 (AHR=1.4, 95% CI: 0.9 to 2.1), advanced HIV disease (WHO III or IV) at enrolment (AHR=2.2, 95% CI: 1.2 to 3.9), and initiation of zidovudine+lamivudine or other cART backbones (unadjusted HR (UHR)=2, 95% CI: 1.2 to 3.2). In contrast, a reduced likelihood of attrition was observed in children with a record of cART changes (UHR=0.2, 95% CI: 0.15 to 0.4). CONCLUSION: A low incidence of attrition was observed in this study. However, the high mortality rate in the first 24 months of treatment and late presentation are concerning. Therefore, data-driven interventions for improving programme quality and outcomes should be prioritised.

Relationship Between Antimicrobial Prescribing and Antimicrobial Resistance Among UTI Patients at Buraidah Central Hospital, Saudi Arabia.

INTRODUCTION: Most of the decisions regarding diagnosis and treatment are based on laboratory test results. Urinary tract infections (UTIs) are among the most common infections in humans. The changing antimicrobial sensitivity in UTI requires appropriate antibiotics. Antimicrobial resistance is an emerging problem in the Kingdom of Saudi Arabia where the complete reversal of antimicrobial resistance is difficult due to irrational use of antibiotics. OBJECTIVES: This study aimed to determine the most common bacterial agents causing UTI in different seasons among patients who were admitted to Buraidah Central Hospital (BCH), Saudi Arabia. The study also evaluated the link between prescribing and resistance toward antimicrobials. MATERIALS AND METHODS: A 6-month retrospective study was conducted among adult patients who were admitted to the inpatient department at BCH. A total of 379 files were collected from microbiological laboratory for inpatients. RESULTS: Most UTI-causing bacteria prevailed in the same season. Of 15 bacterial strains, 12 were significantly correlated with 20 (of a total of 40) antibiotics that were used. Most bacteria were gram-negative. Gram-negative bacilli including Escherichia coli, Klebsiella spp., and Pseudomonadaceae and gram-positive Enterococcus faecalis were most frequently causing UTIs. CONCLUSION: Overall prevalence of antibiotic resistance was negative in bacterial isolates. However, the relationship between antimicrobial prescribing and antimicrobial resistance was significantly negative among UTI patients in BCH, Saudi Arabia.