Epidemiology of herpes simplex virus type 2 in the Middle East and North Africa: Systematic review, meta-analyses, and meta-regressions.

Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with poorly characterized prevalence in the Middle East and North Africa (MENA) region. This study characterized HSV-2 epidemiology in MENA. HSV-2 reports were systematically reviewed as guided by the Cochrane Collaboration Handbook and findings were reported following PRISMA guidelines. Random-effects meta-analyses and meta-regressions were performed to estimate pooled mean outcome measures and to assess predictors of HSV-2 antibody prevalence (seroprevalence), trends in seroprevalence, and between-study heterogeneity. In total, sixty-one overall (133 stratified) HSV-2 seroprevalence measures and two overall (four stratified) proportion measures of HSV-2 detection in laboratory-confirmed genital herpes were extracted from 37 relevant publications. Pooled mean seroprevalence was 5.1% (95% confidence interval [CI]: 3.6%-6.8%) among general populations, 13.3% (95% CI: 8.6%-18.7%) among intermediate-risk populations, 20.6% (95% CI: 5.3%-42.3%) among female sex workers, and 18.3% (95% CI: 3.9%-39.4%) among male sex workers. Compared to Fertile Crescent countries, seroprevalence was 3.39-fold (95% CI: 1.86-6.20) and 3.90-fold (95% CI: 1.78-8.57) higher in Maghreb and Horn of Africa countries, respectively. Compared to studies published before 2010, seroprevalence was 1.73-fold (95% CI: 1.00-2.99) higher in studies published after 2015. Pooled mean proportion of HSV-2 detection in genital herpes was 73.8% (95% CI: 42.2%-95.9%). In conclusion, MENA has a lower HSV-2 seroprevalence than other world regions. Yet, 1 in 20 adults is chronically infected, despite conservative prevailing sexual norms. Seroprevalence may also be increasing, unlike other world regions. Findings support the need for expansion of surveillance and monitoring of HSV-2 infection in MENA.

Epidemiology of herpes simplex virus type 2 in Europe: systematic review, meta-analyses, and meta-regressions.

Background: Herpes simplex virus type 2 (HSV-2) infection is a globally prevalent, life-long, sexually transmitted infection. This study characterized HSV-2 seroprevalence in Europe for various at-risk populations and proportions of HSV-2 detection in genital ulcer disease (GUD) and in genital herpes. Data on neonatal herpes and HSV-2's contribution to HIV transmission were also reviewed. Methods: Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings. The search was conducted in PubMed and Embase databases up to February 20, 2022. Any publication reporting data on the outcome measures was included. Meta-analyses and meta-regressions were conducted. Findings: 211 relevant reports were identified, including 12 overall incidence measures, 294 overall (813 stratified by factors such as age and sex) seroprevalence measures, 13 overall (15 stratified by sex) proportions of HSV-2 detection in clinically diagnosed GUD, and 70 overall (183 stratified by factors such as age and sex) proportions of HSV-2 detection in laboratory-confirmed genital herpes. Pooled mean seroprevalence was 12.4% (95% CI: 11.5-13.3%) among general populations, 27.8% (95% CI: 17.5-39.4%) among men who have sex with men, 46.0% (95% CI: 40.1-51.8%) among people living with HIV and people in HIV discordant couples, and 63.2% (95% CI: 55.5-70.6%) among female sex workers. Most measures showed heterogeneity in HSV-2 seroprevalence. The pooled mean seroprevalence among general populations increased with age and was 0.65-fold (95% CI: 0.58-0.74) lower in men than women. Seroprevalence decreased by 1% per calendar year. Pooled mean proportions of HSV-2 detection in GUD and in genital herpes were 22.0% (95% CI: 15.3-29.6%) and 66.0% (95% CI: 62.9-69.1%), respectively. HSV-2 detection in genital herpes cases was 1.21-fold (95% CI: 1.10-1.32) higher in men compared to women and decreased by 1% per calendar year. Incidence of neonatal herpes indicated an increasing trend. Interpretation: Although seroprevalence is declining, a significant proportion of Europe's population is infected with HSV-2. HSV-2 accounts for approximately one-fifth of GUD cases and two-thirds of genital herpes cases. Findings support the need to invest in HSV-2 vaccine development, and sexual and reproductive health services. Funding: Qatar National Research Fund [NPRP 9-040-3-008] and pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar supported this study.

Status of the HIV epidemic in key populations in the Middle East and north Africa: knowns and unknowns.

The Middle East and north Africa is one of only two world regions where HIV incidence is on the rise, with most infections occurring among key populations: people who inject drugs, men who have sex with men, and female sex workers. In this Review, we show a trend of increasing HIV prevalence among the three key populations in the Middle East and north Africa. Although the epidemic continues at a low level in some countries or localities within a country, there is evidence for concentrated epidemics, with sustained transmission at considerable HIV prevalence among people who inject drugs and men who have sex with men in over half of countries in the region with data, and among female sex workers in several countries. Most epidemics emerged around 2003 or thereafter. The status of the epidemic among key populations remains unknown in several countries due to persistent data gaps. The HIV response in Middle East and north Africa remains far below global targets for prevention, testing, and treatment. It is hindered by underfunding, poor surveillance, and stigma, all of which are compounded by widespread conflict and humanitarian crises, and most recently, the advent of COVID-19. Investment is needed to put the region on track towards the target of eliminating HIV/AIDS as a global health threat by 2030. Reaching this target will not be possible without tailoring the response to the needs of key populations, while addressing, to the extent possible, the complex structural and operational barriers to success.

The design and implementation of an undergraduate health professional degree elective course on scientific writing, peer assessment, and critical appraisal.

BACKGROUND AND PURPOSE: Strong writing skills are critical to the pharmacy profession. This paper describes the design, delivery, and impact of a course intended to develop pharmacy students' scientific writing, peer assessment, and critical appraisal skills. EDUCATIONAL ACTIVITY AND SETTING: The course was offered in the final year of an undergraduate pharmacy program with students whose first language is not English. In this course, students write two structured pharmacy review articles (PRA) based on assigned scientific research articles and peer assess each others' written PRAs. Students also critically appraise scientific research articles on a weekly basis, complete one pre-journal club written reflective critique based on a assigned scientific research article, and moderate one journal club session. FINDINGS: Course rubrics were developed and validated by the course coordinators. A survey administered to students enrolled in the course identified that 85% of the students perceived that they gained adequate writing skills in the course. More than 70% of the students indicated they had the necessary skills to evaluate their peers' written assessments, and 93% felt comfortable providing and receiving feedback from peers. More than 90% of the students indicated that writing PRAs and the peer assessment improved their critical and analytical skills. SUMMARY: This course improved students' scientific writing, peer assessment, and critical appraisal skills. Further practice is required to reinforce the skills learned and to strengthen the writing skills of students.

Endoplasmic Reticulum (ER) Stress-Generated Extracellular Vesicles (Microparticles) Self-Perpetuate ER Stress and Mediate Endothelial Cell Dysfunction Independently of Cell Survival.

Circulating extracellular vesicles (EVs) are recognized as biomarkers and effectors of endothelial dysfunction, the initiating step of cardiovascular abnormalities. Among these EVs, microparticles (MPs) are vesicles directly released from the cytoplasmic membrane of activated cells. MPs were shown to induce endothelial dysfunction through the activation of endoplasmic reticulum (ER) stress. However, it is not known whether ER stress can lead to MPs release from endothelial cells and what biological messages are carried by these MPs. Therefore, we aimed to assess the impact of ER stress on MPs shedding from endothelial cells, and to investigate their effects on endothelial cell function. EA.hy926 endothelial cells or human umbilical vein endothelial cells (HUVECs) were treated for 24 h with ER stress inducers, thapsigargin or dithiothreitol (DTT), in the presence or absence of 4-Phenylbutyric acid (PBA), a chemical chaperone to inhibit ER stress. Then, MPs were isolated and used to treat cells (10-20 µg/mL) for 24-48 h before assessing ER stress response, angiogenic capacity, nitric oxide (NO) release, autophagy and apoptosis. ER stress (thapsigargin or DDT)-generated MPs did not differ quantitatively from controls; however, they carried deleterious messages for endothelial function. Exposure of endothelial cells to ER stress-generated MPs increased mRNA and protein expression of key ER stress markers, indicating a vicious circle activation of ER stress. ER stress (thapsigargin)-generated MPs impaired the angiogenic capacity of HUVECs and reduced NO release, indicating an impaired endothelial function. While ER stress (thapsigargin)-generated MPs altered the release of inflammatory cytokines, they did not, however, affect autophagy or apoptosis in HUVECs. This work enhances the general understanding of the deleterious effects carried out by MPs in medical conditions where ER stress is sustainably activated such as diabetes and metabolic syndrome.

Interplay between Endoplasmic Reticulum Stress and Large Extracellular Vesicles (Microparticles) in Endothelial Cell Dysfunction.

Upon increased demand for protein synthesis, accumulation of misfolded and/or unfolded proteins within the endoplasmic reticulum (ER), a pro-survival response is activated termed unfolded protein response (UPR), aiming at restoring the proper function of the ER. Prolonged activation of the UPR leads, however, to ER stress, a cellular state that contributes to the pathogenesis of various chronic diseases including obesity and diabetes. ER stress response by itself can result in endothelial dysfunction, a hallmark of cardiovascular disease, through various cellular mechanisms including apoptosis, insulin resistance, inflammation and oxidative stress. Extracellular vesicles (EVs), particularly large EVs (lEVs) commonly referred to as microparticles (MPs), are membrane vesicles. They are considered as a fingerprint of their originating cells, carrying a variety of molecular components of their parent cells. lEVs are emerging as major contributors to endothelial cell dysfunction in various metabolic disease conditions. However, the mechanisms underpinning the role of lEVs in endothelial dysfunction are not fully elucidated. Recently, ER stress emerged as a bridging molecular link between lEVs and endothelial cell dysfunction. Therefore, in the current review, we summarized the roles of lEVs and ER stress in endothelial dysfunction and discussed the molecular crosstalk and relationship between ER stress and lEVs in endothelial dysfunction.

Inhibition of p90 ribosomal S6 kinase potentiates cisplatin activity in A549 human lung adenocarcinoma cells.

OBJECTIVE: Cisplatin is a standard treatment approach against lung adenocarcinoma. Resistance to cisplatin and the toxic side effects of cisplatin continue to remain a challenge. Combining drugs with different mechanisms is being investigated as a means to overcome these challenges. In ovarian cancer cells, the knockdown of RSK2 increased the sensitivity of cisplatin. RSK is a downstream mediator of the MAPK pathway that is responsible for cell survival, proliferation and migration. METHODS: Our study examined the effect of cisplatin, BI-D1870 (RSK inhibitor) or their combination on cell migration, apoptosis, autophagy and cell cycle in A549 human lung adenocarcinoma cells. KEY FINDINGS: The combination of cisplatin and BI-D1870 potentiated the antimigration rate, the activation of caspases-3 and was associated with a significant decrease in RSK1 and ERK expression when compared to cisplatin alone. The combination of cisplatin and BI-D1870 also resulted in the inhibition of LC3 II to LC3 I expression when compared to BI-D1870. The combination of cisplatin and BI-D1870 increased the number of cells in the G2/M-phase when compared to cisplatin alone. CONCLUSIONS: These findings suggest that combining cisplatin with agents that target the RSK mediated cell survival pathway, may potentiate the cisplatin effect in lung adenocarcinoma.

CTLA4-Ig (abatacept): a promising investigational drug for use in type 1 diabetes.

Introduction: Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells in the pancreas; it leads to the under or nonproduction of insulin. T1D is associated with numerous life-threatening micro- and macro-vascular complications and early deaths, hence the development of preventative strategies is a priority for research.Areas covered: The authors outline the drawbacks of available treatments for T1D and assess the three key strategies for prevention, including immunomodulatory therapies which hold the most potential. This article examines CTLA4-Ig and its efficacy and safety profiles. Finally, the pharmacokinetic parameters and pharmacodynamic markers of abatacept are shown in vivo and in clinical trials, guiding dosage regimen recommendations for future investigational studies.Expert opinion: Immunomodulation is one of the promising strategies for decelerating the progression of beta-cell destruction after the onset of T1D. It holds the advantage of specific immune modulation without systemic general immunosuppression. Preclinical and clinical studies have yielded promising data on the use of CTLA4-Ig in T1D. Variations in response to CTLA4-Ig might be partially explained by the existence of multiple T1D subtypes with varying baseline innate inflammatory/regulatory bias and the rate of C-peptide decline.

Practice implications of an antimicrobial stewardship intervention in a tertiary care teaching hospital, Qatar.

BACKGROUND: Antibiotic misuse is a worldwide public health problem and has been associated with increased morbidity, length of hospital stay, mortality, healthcare costs, and most importantly antibiotic resistance. AIMS: We aimed to evaluate the compliance of antibiotic prescribing with national guidelines, assess how educational interventions can best be utilized to make impact and fill gaps for optimal antibiotic utilization, and to identify facilitators and barriers to implementing ASPs in Qatar. METHODS: Six cross-sectional baseline audits of antibiotic prescribing were conducted over a two-week period at a tertiary care teaching hospital. A sub-analysis of prescriptions with follow up has followed. An educational intervention utilizing the PDSA (Plan-Do-Study-Act) tool was implemented to address gaps identified. A repeated audit was done to assess the impact of change. Lastly, interviews were conducted to recognize perceived facilitators and barriers for ASP implementation, identify strategies to overcome barriers, and evaluate the effectiveness of educational interventions. RESULTS: The most common indication for antibiotic prescribing was febrile neutropenia (20.7%). The most frequently used class of antibiotics was carbapenems (21.4%). Sixty percent of prescriptions complied with guidelines. The rationale behind choosing not to adhere to guidelines was not documented in 37.2% of cases. Suboptimal documentation in records was targeted through our intervention. The audit post intervention showed slight improvement in documentation. Facilitators and barriers included: collaboration and communication among teams, compliance with guidelines, interventions documented by clinical pharmacists, and electronic system errors. CONCLUSIONS: Effective communication, continuous documentation in records, and repetitive education promote rational antibiotic prescribing and enhance ASPs.

Molecular Mechanisms Underpinning Microparticle-Mediated Cellular Injury in Cardiovascular Complications Associated with Diabetes.

Microparticles (MPs) are small vesicles shed from the cytoplasmic membrane of healthy, activated, or apoptotic cells. MPs are very heterogeneous in size (100-1,000 nm), and they harbor proteins and surface antigens specific to cells they originate from. Virtually, all cells can shed MPs, and therefore, they can be found in all body fluids, but also entrapped in tissues. Of interest and because of their easy detection using a variety of techniques, circulating MPs were recognized as biomarkers for cell activation. MPs were also found to mediate critical actions in intercellular communication and transmitting biological messages by acting as paracrine vehicles. High plasma numbers of MPs were reported in many cardiovascular and metabolic disturbances that are closely associated with insulin resistance and low-grade inflammation and have been linked to adverse actions on cardiovascular function. This review highlights the involvement of MPs in cardiovascular complications associated with diabetes and discusses the molecular mechanisms that underpin the pathophysiological role of MPs in the onset and progression of cellular injury in diabetes.

The use of Socrative and Yammer online tools to promote interactive learning in pharmacy education.

BACKGROUND AND PURPOSE: Engagement of students in the didactic classroom setting restricts students' time spent towards active learning, which in turn, adversely affects the retention of concepts taught through traditional teaching methods. Thus, interactive learning is used as an alternative to engage students in the classroom and to enrich their learning experience. Integrating interactive learning activities has been shown to facilitate student learning and improve the learning outcomes. The objectives of this study are to assess the perceptions of students on the benefits and appropriateness of using online tools (e.g., Socrative and Yammer) to promote interaction of students with the instructor and other students in the classroom setting. EDUCATIONAL ACTIVITY AND SETTING: Students enrolled in the second and third professional years of the bachelor of pharmacy program at Qatar University were introduced to various interactive learning tools in two Pharmaceutical Sciences courses. Students were then surveyed to assess their perceptions about the benefits and appropriateness of the respective interactive learning tools introduced in the courses. FINDINGS: Our survey results indicate that the students are in favor of using online educational tools and believe that the use of interactive learning tools enhances their learning experience. SUMMARY: Pharmacy students at Qatar University perceive that the incorporation of online technology in Pharmaceutical Sciences courses enhances interactive learning in the classroom setting.