by Young Bin Joo, Junho Lee, Yune-Jung Park, So-Young Bang, Kwangwoo Kim, Hye-Soon Lee …

by Yichen Zhong, Lorna Wilkinson-White, Esther Zhang, Biswaranjan Mohanty, Belinda B. Zhang, Madeline S. McRae, Rachel Luo, Thomas A. Allport, Anthony P. Duff, Jennifer Zhao, Serene El-Kamand, Mar-Dean Du Plessis, Liza Cubeddu, Roland Gamsjaeger, Sandro F. Ataide, Ann H. Kwan RNA-binding proteins (RBPs) are a major class of proteins that interact with RNAs to change their fate or function. RBPs and the ribonucleoprotein complexes they constitute are involved in many essential cellular processes. In many cases, the molecular details of RBP:RNA interactions differ between viruses, prokaryotes and eukaryotes, making prokaryotic and viral RBPs good potential drug targets. However, targeting RBPs with small molecules has so far been met with limited success as RNA-binding sites tend to be extended, shallow and dynamic with a mixture of charged, polar and hydrophobic interactions. Here, we show that peptide nucleic acids (PNAs) with nucleic acid-like binding properties and a highly stable peptide-like backbone can be used to target some RBPs. We have designed PNAs to mimic the short RNA stem-loop sequence required for the initiation of prokaryotic signal recognition particle (SRP) assembly, a target for antibiotics development. Using a range of biophysical and biochemical assays, the designed PNAs were demonstrated to fold into a hairpin structure, bind the targeted protein and compete with the native RNA hairpin to inhibit SRP formation. To show the applicability of PNAs against other RBPs, a PNA was also shown to bind Nsp9 from SARS-CoV-2, a protein that exhibits non-sequence-specific RNA binding but preferentially binds hairpin structures. Taken together, our results support that PNAs can be a promising class of compounds for targeting RNA-binding activities in RBPs.

Abstract Background In Senegalese high-burden regions, the existing package of interventions is insufficient to reach the malaria elimination goal. Asymptomatic carriers of Plasmodium contribute significantly to malaria persistence and are not targeted by current interventions. The systematic treatment of all individuals in a community (mass drug administration, MDA) is a relevant intervention to tackle asymptomatic infections. The intervention can only be effective with a high participation of the population and, therefore, depends largely on its acceptability. This study aims to investigate the prospective acceptability of MDA in the Kedougou region to inform its potential use in a future strategy. Methods Following a 7-construct theoretical framework, prospective acceptability of MDA implemented in the rainy season was studied. In four villages, a sequential mixed design, from qualitative to quantitative, was used. In November 2021, interviews with healthcare professionals and focus groups with villagers were conducted. Findings from thematic analysis informed the development of a questionnaire administered to individuals aged ≥ 15 years in March 2022. Based on the questionnaire, an acceptability score was constructed and associations with socio-demographic factors were investigated using a linear mixed model. Results The 7 interviews, the 12 focus groups, and the questionnaire administered to 289 individuals demonstrated a good acceptability of MDA. Two potential barriers were identified: the contradiction of taking a medication without feeling sick and the occurrence of side effects; and four facilitators: the perception of malaria as a burden, a good understanding of MDA, a good perceived effectiveness, and the resulting economic benefits. The average acceptability score was 3.5 (range from -7 to + 7). Young adults aged 15 to 21 had a lower acceptability score compared to the other age groups, indicating an additional barrier to acceptability (β = -0.78 [-1.67;0.1]). Conclusion MDA is a priori acceptable to communities of Kedougou region in Senegal. Sensitization campaigns co-constructed with the communities, especially targeting young adults, are essential to ensure good acceptability. …

IntroductionThe WHO estimates a gap of about 30% between the incident (10.6 million) and notified (7.5 million) cases of tuberculosis (TB). Combined with the growing recognition in prevalence surveys of the high proportion of cases identified who are asymptomatic or paucisymptomatic, these data underscore how current symptom screening approaches and use of diagnostic tests with suboptimal performance on sputum miss large numbers of cases. Thus, the development of sputum-free biomarker-based tests for diagnosis is becoming necessary, which the WHO has already identified as a priority for new TB diagnostics. The objective of this study is to evaluate a combination of exhaled breath condensate (EBC) samples and mycobacterial lipoarabinomannan (LAM) as point-of-care (POC) assays to identify TB patients. Methods and analysisThis prospective diagnostic accuracy study is conducted at the TB Screening and Treatment Centre of International Center for Diarrhoeal Disease Research, Bangladesh, on a cohort of adults and adolescents >11 years of age. A total of 614 individuals with presumptive pulmonary TB based on TB signs, symptoms and radiography are being recruited from 28 August 2023. Spot sputum is collected for standard reference testing (L-J culture, GeneXpert MTB/Rif, acid-fast Bacilli microscopy) to fine-tune categorisation of TB disease status for each participant, defined as (1) definite TB (at least one positive standard reference test); (2) probable TB (not microbiologically confirmed but under TB treatment); (3) possible TB (no TB treatment but signs, symptoms and radiography suggestive of TB); (4) other respiratory disease (microbiologically not confirmed and no radiography presenting abnormalities compatible with TB); and (5) unknown (no microbiological evidence with normal/no TB abnormalities with radiography). Urine and EBC specimens will be subjected to LAM POC testing and biobanked for further investigation. Statistical analyses will include an assessment of diagnostic accuracy by constructing receiver operating curves and calculating sensitivity and specificity, as well as post-test probabilities. Ethics and disseminationThe study protocol was approved by the Research Review Committee as well as the Ethical Review Committee of icddr,b and recorded under a protocol reference number, PR-2301. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings, and shared with national and international policymaking bodies. …

Abstract To assess the safety of varicella vaccine (VarV) by conducting post-marketing surveillance on adverse events following immunization (AEFI) in Jiangsu Province, China. Methods We utilized the AEFI Information System of mainland China to monitor and categorize adverse reactions associated with VarV. Results The incidence rate of AEFI was significantly higher after the first dose (48.79/100,000 doses) compared to the second dose (45.18/100,000 doses) (χ2 = 4.63, P = 0.031). Regional variations in AEFI incidence were observed within Jiangsu Province. Common reactions comprised 90.96% of AEFIs, while rare reactions and coincidental events accounted for 6.59% and 0.51%, respectively. Notably, there were no adverse events linked to vaccine quality, program errors, psychogenic reactions, or fatalities. Over 96% of AEFIs occurred within three days of VarV administration, with redness at the injection site (2.6 cm to 5 cm in diameter) being the most frequently observed symptom. Conclusion VarV demonstrates a commendable safety profile. Although there was a slight increase in AEFI incidence between 2022 and 2023, common vaccine reactions were predominantly observed, and the rates of rare reactions remained very low. …

Abstract Background Mycoplasma genitalium (MG), a sexually transmitted infection (STI), has emerged as a common cause of non-gonococcal urethritis and cervicitis worldwide, with documented resistance to commonly used antibiotics including doxycycline and azithromycin. Data in Ghana regarding the prevalence of MG is limited. Methods This retrospective study investigated MG presence and macrolide resistance among patients who previously reported to selected clinics for STI symptoms between December 2012 and June 2020. Samples were screened for MG and mutations associated with azithromycin resistance were investigated using Nucleic Acid Amplification Testing (NAAT) including the Resistance Plus MG® kit from SpeeDx and the LightMix® kit for MG, combined with the Modular Mycoplasma Macrolide from TIB Molbiol. Results A total of 1,015 samples were screened, out of which MG infection rate by TIB Molbiol and SpeeDx were 3.1% and 3.4%, respectively. The mutation responsible for macrolide resistance was detected in one MG positive sample by both assays. Both diagnostic tests revealed no significant association between MG infection and socio-demographic characteristics, clinical symptoms, gonorrhea, and chlamydia infection status. There was no significant difference in the mycoplasma percentage positivity rate detected using SpeeDx (3.4%) and TIB Molbiol (3.1%). Conclusions While not commonly tested as a cause of STI symptoms, MG is widespread in Ghana, exhibiting symptoms and prevalence comparable to those in other countries and linked to antimicrobial resistance. Future research using various molecular techniques is essential to monitor resistance trends and guide future antibiotic choices. …

Abstract Background The latent tuberculosis infection (LTBI) burden is still unclear in schoolchildren and adolescents in China. Previous study and daily surveillance data indicate a LTBI detection gap. The research objective was to evaluate the LTBI burden and detection gap among schoolchildren and adolescents in China. Methods A cross-sectional study was conducted among 69,667 schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 implemented by Chongqing Municipal Institute of Tuberculosis using tuberculin skin test (TST) and creation tuberculin skin test (C-TST). To evaluate the LTBI detection gap, the pulmonary tuberculosis (PTB) screening data implemented by Chongqing Municipal Institute of Tuberculosis have been compared with the data in 2021 implemented by community-level medical and health care institutions. Results The LTBI prevalence rate using TST and C-TST implemented by Chongqing Municipal Institute of Tuberculosis was 12.8% (95%CI, 12.5-13%) and 6.4% (95%CI, 6-6.8%) respectively. The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions (χ2 = 2931.9, P 

Abstract Background Antiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). Methods This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline. Results Thirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA 

Abstract Background Cystic echinococcosis (CE) is prevalent in livestock farming regions around the world. However, it remains relatively rare compared to other infectious diseases. CE typically affects the liver, lungs, brain, and kidneys. Spinal and pleural wall involvement is exceedingly rare. We report a unique case of intradural and pleural wall CE in a young male, successfully treated with surgery and postoperative medication. Case presentation A 19-year-old Tibetan male from the Qinghai-Tibet Plateau was diagnosed with intradural and pleural wall CE through imaging, serology, and surgical pathology. According to the Dew/Braithwaite & Lees (BL) classification, his condition was an exceptionally rare form of spinal echinococcosis, compounded by an even rarer pleural wall involvement. Prompt surgical intervention and postoperative medication resulted in significant improvement in spinal cord compression symptoms. Conclusions This case highlights the diagnostic and therapeutic challenges of rare CE locations. MRI proved superior to CT in diagnosing bony cystic echinococcosis. Early surgical intervention combined with medication facilitates spinal cord function recovery, providing valuable insights for managing similar cases. …

IMPORTANCE: The relationship between post-hospital arrival factors and out-of-hospital cardiac arrest (OHCA) outcomes remains unclear. OBJECTIVES: This study assessed the impact of post-hospital arrival factors on OHCA outcomes during the COVID-19 pandemic using a prediction model. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, data from the All-Japan Utstein Registry, a nationwide population-based database, between 2015 and 2021 were used. A total of 541,781 patients older than 18 years old who experienced OHCA of cardiac origin were included. MAIN OUTCOMES AND MEASURES: The primary exposure was trends in COVID-19 cases. The study compared the predicted proportion of favorable neurologic outcomes 1 month after resuscitation with the actual outcomes. Neurologic outcomes were categorized based on the Cerebral Performance Category score (1, good cerebral function; 2, moderate cerebral function). RESULTS: The prediction model, which had an area under the curve of 0.96, closely matched actual outcomes in 2019. However, a significant discrepancy emerged after the pandemic began in 2020, where outcomes continued to deteriorate as the virus spread, exacerbated by both pre- and post-hospital arrival factors. CONCLUSIONS AND RELEVANCE: Post-hospital arrival factors were as important as pre-hospital factors in adversely affecting the prognosis of patients following OHCA during the COVID-19 pandemic. The results suggest that the overall response of the healthcare system needs to be improved during infectious disease outbreaks to improve outcomes.

IMPORTANCE: Acute respiratory distress syndrome (ARDS) is associated with high mortality and morbidity. Extracorporeal membrane oxygenation (ECMO) is one of the interventions that have been in practice for ARDS for decades. OBJECTIVES: The purpose of the study was to investigate the outcomes of ECMO in pediatric trauma patients who suffered from ARDS. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: The Trauma Quality Improvement Program database for years 2017 to 2019 and 2021 through 2022 was accessed for the study. All children younger than 18 years old who were admitted to the hospital after trauma and suffered from ARDS were included in the study. Other variables included in the study were patients’ demographics, clinical characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, comorbidities, and outcomes. MAIN OUTCOMES AND MEASURES: ECMO is the exposure, and the outcomes are in-hospital mortality and hospital complications (acute kidney injury [AKI], pneumonia and deep vein thrombosis [DVT]). RESULTS: Of 453 patients who qualified for the study, propensity score matching found 50 pairs of patients. There were no significant differences identified between the groups, ECMO+ vs. ECMO– on patients’ age in years (16 yr; interquartile range [IQR], 13.25–17 yr vs. 16 yr [14.25–17 yr]), race (White; 62.0% vs. 66.0%), sex (male; 78% vs. 76%), ISS (23 [IQR, 9.25–34] vs. 22 [9.25–32]), and GCS (15 [IQR, 3–15] vs. 13.5 [3–15]), mechanism of injury; and comorbidities. There was no difference between the groups, ECMO+ vs. ECMO–, in-hospital mortality (10.0% vs. 20.0%; p = 0.302), hospital complications (AKI 12.0% vs. 2.0%; p = 0.131), pneumonia (10.0% vs. 20.0%; p = 0.182 > ), and DVT (16% vs. 6%; p = 0.228). CONCLUSIONS AND RELEVANCE: No difference in mortality was observed in injured children who suffered from the ARDS and were placed on ECMO when compared with patients who were not placed on ECMO. Patients with trauma and ARDS who require ECMO have comparable outcomes to those who do not receive ECMO. A larger sample size study is needed to find the exact benefit of ECMO in this patients’ cohort.

OBJECTIVES: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN: Retrospective analysis of data from prospective clinical studies. SETTING: Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, β was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

IMPORTANCE: In the setting of an active pandemic the impact of public vaccine hesitancy on healthcare workers has not yet been explored. There is currently a paucity of literature that examines how patient resistance to disease prevention in general impacts practitioners. OBJECTIVES: The COVID-19 pandemic created unprecedented healthcare challenges with impacts on healthcare workers’ wellbeing. Vaccine hesitancy added complexity to providing care for unvaccinated patients. Our study qualitatively explored experiences of healthcare providers caring for unvaccinated patients with severe COVID-19 infection in the intensive care setting. DESIGN: We used interview-based constructivist grounded theory methodology to explore experiences of healthcare providers with critically ill unvaccinated COVID-19 patients. SETTING AND PARTICIPANTS: Healthcare providers who cared for unvaccinated patients with severe COVID-19 respiratory failure following availability of severe acute respiratory syndrome coronavirus 2 vaccines were recruited from seven ICUs located within two large academic centers and one community-based hospital. We interviewed 24 participants, consisting of eight attending physicians, seven registered nurses, six critical care fellows, one respiratory therapist, one physiotherapist, and one social worker between March 2022 and September 2022 (approximately 1.5 yr after the availability of COVID-19 vaccines in Canada). ANALYSIS: Interviews were recorded, transcribed, de-identified, and coded to identify emerging themes. The final data was analyzed to generate the thematic framework. Reflexivity was employed to reflect upon and discuss individual pre-conceptions and opinions that may impact collection and interpretation of the data. RESULTS: Healthcare providers maintained dedication toward professionalism during provision of care, at the cost of suffering emotional turmoil from the pandemic and COVID-19 vaccine hesitancy. Evolving sources of stress associated with vaccine hesitancy included ongoing high volumes of critically ill patients, resource shortages, and visitation restrictions, which contributed to perceived emotional distress, empathy loss, and professional dissatisfaction. As a result, there were profound personal and professional consequences for healthcare professionals, with perceived impacts on patient care. CONCLUSIONS: Our study highlights struggles of healthcare providers in fulfilling professional duties while navigating emotional stressors unique to vaccine hesitancy. System-based interventions should be explored to help providers navigate biases and moral distress, and to foster resilience for the next major healthcare system strain.

Objective: Evaluate the clinical utility of patient-collected dried blood spots (DBS) in measuring HIV-1 viral load (VL) for monitoring antiretroviral therapy (ART) compared to provider-collected DBS and blood plasma. Design: In a randomized trial of community-based delivery of ART in South Africa, we assessed performance of: (1) DBS specimens compared to plasma, and (2) participant-collected versus staff-collected DBS specimens, to measure HIV-1 VL. Methods: The bioMérieux NucliSENS EasyQ HIV-1 v2.0 assay was used for VL measurement. From October 2017 to November 2019, we collected 996 pairs of plasma/DBS specimens from 760 participants and 315 pairs of staff-/participant-collected DBS cards from 261 participants. We assessed DBS test sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using the WHO failure threshold of 1000 copies/mL. Log-transformed VL was compared using concordance correlation coefficients (CCC) and mean differences from linear mixed models. Results: In a population with 13% detectable VL, DBS VL compared with plasma VL had 91% (95% CI: 86–95) sensitivity, 99% (98–100) specificity, 94% (90–98) PPV, and 99% (98–99) NPV. We observed high agreement between staff-collected DBS VL and plasma VL (CCC: 0.94), and between participant-collected DBS VL and plasma VL (CCC: 0.92). Correlation between participant- and staff-collected DBS was very high (CCC: 0.97; mean difference for those with a detectable result: -0.10 log10 copies/mL [-0.21–0.02]). Conclusions: VL results from participant-collected DBS are clinically comparable with those collected by clinical staff and using blood plasma. Self-collected DBS has potential for use for ART monitoring outside the clinic. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: To understand the relationship between cardiovascular disease (CVD) risk and liver steatosis and fibrosis among people living with HIV (PLWH) ≥40 years on antiretroviral therapy (ART) in low- and middle-income countries (LMIC). Design: We used cross-sectional behavioral and clinical data collected during study enrollment visits in 2020-2022 for the Sentinel Research Network of International epidemiology Databases to Evaluate AIDS (SRN of IeDEA). Methods: Ten-year CVD risk was calculated using 2019 World Health Organization non-laboratory and laboratory models. Transient elastography (TE) was used to assess liver disease. Presence of steatosis and significant fibrosis were defined by Controlled Attenuation Parameter (CAP) ≥248 dB/m and liver stiffness measurement (LSM) ≥7.1 kPa, respectively. Participants with viral hepatitis, hazardous alcohol consumption and unsuppressed HIV viral load were excluded from the analysis. Logistic regression was used to estimate odds ratios, adjusting for study site, CD4 T cell count, stavudine and didanosine exposure, and in models stratified by sex and geographic region. Results: There were 1,750 participants from nine LMIC. Median CVD risk was 3% for both non-laboratory and laboratory-based models. Adjusted odds ratios (ORs) for steatosis and significant fibrosis associated with laboratory CVD risk (≥10% vs.

Background: The decreased mortality of people living with HIV (PLWH) has revealed non-HIV-associated comorbidities such as neurocognitive disorders (e.g., dementia). There is an urgency to discover therapeutics to prevent or delay neurocognitive decline among PLWH. Methods: The artificial intelligence platform Automatic Graph-mining And Transformer based Hypothesis Generation Approach (AGATHA) was utilized to seek potential drugs to be repurposed for the management of non-HIV-associated dementia. AGATHA revealed angiotensin-converting enzyme inhibitors that cross the blood-brain barrier (BBB ACEi) as a target for decreasing dementia. Subsequently, we conducted a retrospective study evaluating incident dementia using the VA Informatics and Computing Infrastructure (VINCI) evaluating ACE inhibitors. Cox proportional hazards models were fit and hazard ratios (HR) with corresponding 95% confidence intervals (CIs) are presented. Findings: A total 9,419 PLWH exposed to an BBB ACE inhibitor (ACEi) and 8,831 PLWH unexposed demonstrated that PLWH exposed to BBB ACEi had a 21.4% (univariate) and 15.2% (multivariate) lower hazard of dementia. The propensity score matched analysis demonstrated a 14.3% lower hazard of incident dementia compared to BBB ACEi unexposed (HR 0.857, 95% CI 0.747–0.984). Interpretation: An artificial intelligence-based literature mining system (AGATHA) was utilized to uncover a medication with potential to be repurposed. AGATHA demonstrated that BBB ACEi as a target for decreasing dementia among PLWH. Additionally, we conducted a retrospective study demonstrating a decrease in incident dementia among PLWH exposed to BBB ACEi. Future research is needed to explore further and understand the relationship of dementia among PLWH exposed to ACEi. JOURNAL/aids/04.03/00002030-990000000-00551/figure1/v/2024-09-09T104253Z/r/image-jpeg Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

The AvrE family of type III secreted effectors are highly conserved among many agriculturally important phytopathogenic bacteria. Despite their critical roles in the pathogenesis of phytopathogenic bacteria, the molecular functions and virulence mechanisms of these effectors have been largely unknown. However, recent studies have identified host-interacting proteins and demonstrated that AvrE family effectors can form water-permeable channels in the plant plasma membrane (PM) to create a hydrated and nutrient-rich extracellular space (apoplast) required for disease establishment. Here, we summarize these recent discoveries and highlight open questions related to AvrE-targeted host proteins.

IntroductionAcupuncture is widely used for metabolic-associated fatty liver disease (MAFLD) treatment; however, the clinical efficacy has not been confirmed due to the lack of high-level evidence-based clinical practice. The purpose of this study is to design a research protocol that will be used to determine the efficacy of acupuncture versus sham acupuncture (SHA) for MAFLD treatment. Methods and analysisThis will be a multicentre, randomised and sham-controlled trial. Ninety-eight participants with MAFLD will be enrolled in this trial. Participants will be randomly assigned in a 1:1 ratio to receive acupuncture or SHA for 12 weeks. The primary outcome is the rate of patients with a 30% relative decline in liver fat after 12 weeks of treatment in MRI-proton density fat fraction (MRI-PDFF), which will be obtained by quantitative chemical shift imaging such as the multipoint Dixon method at 0, 12 and 24 weeks. Secondary outcomes include the changes in the relative liver fat content measured by MRI-PDFF, magnetic resonance elastography, liver function, lipid metabolism, homeostatic model assessment for insulin resistance (HOMA-IR) and serum high sensitivity C reactive protein, which will be obtained at 0, 6, 12 and 24 weeks. Body measurement indicators (body mass index, waist circumference, hip circumference and waist-to-hip ratio) will be obtained at 0, 3, 6, 9, 12 and 24 weeks. The alteration in the gut microbiota composition and its metabolism will be assessed by 16S ribosomal RNA sequencing and liquid chromatography-mass spectrometry at 0 and 12 weeks. Ethics and disseminationThis study protocol has been approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (2023-1347-114-01). The results of this study will be published in a peer-reviewed journal and presented at academic conferences. Trial registration numberChiCTR2300075701. …

IntroductionDespite significant progress over past decades, neonatal and infant morbidity and mortality remain unacceptably high in Ethiopia. Simple interventions have been shown to improve the health of children and reduce mortality. These include promotion of exclusive breast feeding for the first 6 months of life, immunisation and utilisation of available newborn healthcare services, which are proven to improve newborn survival. This study aims to determine the impact of a behaviour change intervention that partners Orthodox priests with volunteer community health workers, known in Ethiopia as the Health Development Army and trains them to conduct newborn health outreach to improve care seeking, uptake of key interventions and identification of sick infants. MethodsThe study designed is a community-randomised trial conducted in the Central Gondar area. The behaviour change intervention pairs trained Orthodox priests with members of the Health Development Army to conduct community health outreach by identifying near-term pregnant women in their communities and educating them on the topics of exclusive breast feeding, immunisation, nutrition and uptake of available child healthcare services. The evaluation of the intervention will enrol up to 150 newborn–mother pairs from communities receiving the behaviour change intervention and another 150 pairs enrolled from control communities. The quantitative analysis will be done by comparing data between the intervention and control groups related to breast feeding, anthropometry, immunisation status and uptake of child health services. The primary outcomes are exclusive breastfeeding through 6 months, mid-upper arm circumference, completion of vaccinations and infant hospitalisation. Ethics and disseminationEthical approval has been obtained from the University of Washington (STUDY00006942) and the University of Gondar (No.V/P/RCS/05/2523/2019) Institutional Review Boards. Oral consent was obtained for the formative study, whereas written consent (or witnessed thumbprint) will be obtained from all enrolled mothers. Results will be communicated to community members, relevant government agencies and other stakeholders. Trial registration numberNCT05111899. …

IntroductionBreastfeeding is crucial in infant nutrition and bonding, recommended for at least 6 months and up to 2 years postpartum, providing health benefits for both infants and mothers. However, nipple trauma is common among lactating mothers. Moisturising therapies, such as hydrogel application, aim to promote the healing of nipple wounds. Despite various interventions proposed, comprehensive reviews evaluating the efficacy of moisturising therapies for nipple trauma are lacking. This review aims to appraise the effectiveness of moisturising therapy, particularly tailored for nipple trauma in lactating women. Methods and analysisThis systematic review protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and is registered in the International Prospective Register of Systematic Reviews. The focus will be on both randomised and non-randomised controlled trials addressing the treatment of nipple trauma in lactating women. In this context, ‘moisturising therapy’ is categorised as a non-pharmacological intervention applied directly to the nipple, excluding treatments for bacterial or fungal infections. The primary outcomes will include measures of the healing efficiency of nipple trauma and reduction in nipple pain. Searches will be conducted without date restrictions across multiple databases, including PubMed, CINAHL, the Cochrane Library, Web of Science, CiNii Research and Ichushi-Web, in addition to exploration of grey literature. Two independent reviewers will manage all stages of the review process, under the supervision of a third reviewer. Data extraction will encompass participant demographics, study methodologies, sample specifics and measured outcomes. Quality assessment will be conducted using the Joanna Briggs Institute Appraisal Checklist Tools. Ethics and disseminationEthics approval is not required for this study. The findings of this review will be disseminated through academic publications, detailed reports and presentations at relevant conferences. PROSPERO registration numberCRD42023481761. …

PurposeEpigenetic modifications including DNA methylation (DNAm) are proposed mechanisms by which social or environmental exposures may influence health and behaviours as we age. The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) DNAm cohort, established in 2013, is one of several worldwide, nationally representative prospective studies of ageing with biological samples from participants who consented to multiomic analysis. ParticipantsNICOLA recruited 8478 participants (8283 aged 50 years or older and 195 spouses or partners at the same address aged under 50 years). Computer-Assisted Personal Interviews, Self-Completion Questionnaires and detailed Health Assessments (HA) were completed. Of the 3471 (44.1%) participants who attended the HA in wave 1, which included venous blood sampling, 2000 were identified for the DNAm cohort. Following technical and data quality control checks, DNAm data are currently available for n=1870. Findings to dateThere was no significant difference based on age, self-reported gender, education, employment, smoking or alcohol status and subjective health reports between the DNAm cohort and other HA attendees. Participants were more likely to be in the DNAm group if they lived with one other person (OR 1.26, 95% CI 1.07 to 1.49). The DNAm group had a lower proportion of depressed participants and those meeting criteria for post-traumatic stress disorder (11.7% and 4.4% vs 13.5% and 4.5%, respectively) categorised by objective assessment tools but this was not significant (OR 0.84, 95% CI 0.69 to 1.02 and OR 0.87, 95% CI 0.64 to 1.19). Future plansThe deeply phenotyped DNAm cohort in NICOLA with planned prospective follow-up and additional multiomic data releases will increase the cohort’s utility for research into ageing. The genomic and epigenetic data for the DNAm cohort has been deposited on the European Genome-Phenome Archive, increasing the profile of this cohort and data availability to researchers. …

Abstract Background Understanding the aetiological organisms causing maternal infections is crucial to inform antibiotic treatment guidelines, but such data are scarce from Sub-Saharan Africa (SSA). We performed this systematic review and meta-analysis to address this gap. Methods Microbiologically confirmed maternal infection data were collected from PubMed, Embase, and African Journals online databases. The search strategy combined terms related to bacterial infection, pregnancy, postnatal period, observational studies, SSA. Exclusion criteria included colonization, asymptomatic infection, and screening studies. Pooled proportions for bacterial isolates and antimicrobial resistance (AMR) were calculated. Quality and completeness of reporting were assessed using the Newcastle–Ottawa and STROBE checklists. Findings We included 14 papers comprising data from 2,575 women from four sources (blood, urine, surgical wound and endocervical). Mixed-growth was commonly reported at 17% (95% CI: 12%-23%), E. coli from 11%(CI:10%-12%), S. aureus from 5%(CI: 5%-6%), Klebsiella spp. at 5%(CI: 4%- 5%) and Streptococcus spp. at 2%(CI: 1%-2%). We observed intra-sample and inter-sample heterogeneity between 88–92% in all meta-analyses. AMR rates were between 19% -77%, the highest with first-line beta-lactam antibiotics. Convenience sampling, and limited reporting of laboratory techniques were areas of concern. Interpretation We provide a comprehensive summary of microbial aetiology of maternal infections in SSA and demonstrate the paucity of data available for this region. We flag the need to review the current local and international empirical treatment guidelines for maternal bacterial infections in SSA because there is high prevalence of AMR among common causative bacteria. Funding This research was supported by the NIHR-Professorship/NIHR300808 and the Wellcome-Strategic-award /206545/Z/17/Z. Trial registration Prospero ID CRD42021238515. …

Abstract Background Even though the disease has spread throughout the world, with millions killed, global COVID-19 vaccination coverage remains low, particularly in developing countries. However, epidemiological data is lacking in the area. Hence, this study aimed to assess COVID-19 uptake, willingness for vaccination, and associated factors. Method A hospital-based cross-sectional study was conducted from May 1 to June 30, 2022, among patients attending chronic follow-up clinics in the two comprehensive specialized hospitals in Bahir Dar. The total sample size was 423. Participants were selected by a systematic random sampling technique. Data was gathered using a pre-tested questionnaire and analyzed using SPSS version 23. A descriptive analysis was performed. A binary logistic regression analysis was done to assess the association between variables. Variables with a p-value 

Abstract Background In Ethiopia, there were an estimated 670,906 people living with the Human Immune Virus (HIV). Implementing an HIV test and treat strategy and rapid scale-up of anti-retroviral treatment (ART) provided health facilities increased the number of the number of people living with HIV/AIDS. In the same way, the expansion of viral load monitoring in these health facilities and poor adherence to ART increase the number of high-viral load (HVL) patients. To alleviate this problem, the World Health Organization (WHO) recommended EAC intervention for HVL patients. Therefore, the aim of this research was to determine the level of healthcare providers’ adherence to the EAC intervention protocol and explore barriers and facilitators of the intervention in West Amhara, Northwest Ethiopia. Method Descriptive cross-sectional study design with concurrent mixed-method evaluation was employed. The adherence dimension, with its sub-dimensions of content, coverage, frequency, and duration of the EAC intervention, was used with sixteen indicators. A total of 20 high-case-load public health facilities and 173 HVL patients were included in our study. Quantitative data was entered into Epi Info and exported to SPSS version 25 for analysis. Descriptive statistics are analyzed in terms of frequencies, percentages, variances, and means and presented as narrations, frequency tables, graphs, and charts. Qualitative data were transcribed, translated, coded, and analyzed thematically using Open Code version 4.0 software. The qualitative findings were used to triangulate the quantitative findings. Result The average adherence level of health care providers (HCPs) to the EAC intervention protocol was 55.3%, from which content, coverage, frequency, and duration of the intervention contributed 70.3%, 86.3%, 36.9%, and 27.7%, respectively. Most of the intervention contents were delivered during the session, but none of the providers developed a patient adherence plan at the end of the session. All HVL patients were linked and enrolled in the EAC intervention. But only 6% of them were tested for repeat VL. Conclusion The average adherence level of HCPs to the EAC intervention protocol was very inadequate. The main gap identified was difficulties in completing the EAC intervention sessions based on schedules. Implementing adherence improvement strategies, assigning an adequate number of EAC providers in ART and Prevention of Mother-to-Child Transmission (PMTCT) clinics, and allowing sufficient time during EAC sessions are important. …

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases. Methods From January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance. Results The multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452–4.360), elevated serum PT (p 

The gut microbiome contains numerous bacteria tied to our health. However, genetically modifying this community remains a major challenge. Brödel et al. take a critical step by engineering bacteriophages to efficiently deliver gene editors without propagation of the genetic cargo, efficiently introducing edits to bacteria residing in the mouse gut.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a unique asexual blood-stage malaria vaccine candidate because of its high conservation and essential biological function of binding to basigin on the erythrocyte surface. Recent studies by Barrett et al., Wang et al., and King et al., have brought RH5-based vaccine development a step forward based on a rational antigen design strategy.

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

Publication date: Available online 13 September 2024 Source: Infectious Disease Modelling Author(s): Julio Cezar Souza Vasconcelos, Silvio Aparecido Lopes, Juan Camilo Cifuentes Arenas, Maria Fátima das Graças Fernandes da Silva …

by Zhongyang He, Jonathan M. Heess, Travis Young, Zhen Lei The COVID-19 pandemic introduced imminent and lasting impacts on the opioid crisis in the U.S., including a significant increase in opioid overdose and deaths and in use of telehealth in treatment. What lessons can we learn from the treatment transition during the pandemic that could help tackle the opioid crisis when future pandemics strike? In this paper, we conducted a phone survey with opioid treatment facilities in Pennsylvania to examine the COVID-19’s impacts on treatment facilities and individuals with opioid use disorder during the first year of the pandemic. We separated the lockdown period (Mid-March through Mid-May, 2020) from the reopening period that followed, and urban areas from rural areas, to explore temporal evolution and rural-urban variations in the COVID-19’s impacts. We found rural-urban heterogeneity in facilities’ adoption of telehealth in treatment and in challenges and risk factors faced by their clients during the lockdown period. During the reopening, telehealth was adopted by most facilities, and telehealth-related challenges became less salient; however, both rural and urban facilities reported higher relapse risks faced by their clients, citing factors more likely to be at clients’ end and related to socioeconomic stressors and mental health. Our results highlight the vitality of addressing socioeconomic and mental health challenges faced by individuals with OUD, via government policies and community interventions, when future pandemics strike. The findings also indicate the importance of maintaining facilities’ financial well-being to provide treatment services.

by Temesgen Leka Lerango, Tesfalidet Markos, Daniel Yehualeshet, Endashaw Kefyalew, Semalgn Leka Lerango Background Globally, HIV infection remains a leading cause of morbidity and mortality. Despite reducing new infections, the global response to advanced HIV disease (AHD) remains ineffective, leaving HIV epidemics a significant public health threat worldwide. In Ethiopia, evidence regarding AHD is scarce. Therefore, this study aimed to assess the prevalence and predictors of AHD among newly diagnosed people living with HIV (PLHIV) initiating antiretroviral therapy in the Gedeo zone, southern Ethiopia. Methods A facility-based cross-sectional study was conducted from May 29, 2023, to February 06, 2024, at health facilities providing HIV care in the Gedeo zone, southern Ethiopia. A total of 427 PLHIV-initiating antiretroviral therapy (ART) were recruited for the study. The data were collected through face-to-face interviews and record reviews using KoboCollect version 2.4 and analyzed using R version 4.3.3. The Akaike information criterion (AIC) model selection was used to evaluate and choose the best-fitting model to describe the relationship between AHD and predictors. Finally, variables with a p-value less than 0.05 were considered independent predictors in the multivariable regression analysis. Results The study participants’ mean (±SD) age was 31.3 (±8.7) years. The overall prevalence of AHD among newly diagnosed PLHIV-initiating ART was 34.4% (95% CI: 29.8%, 39.1%). Rural residence (AOR = 3.48, 95% CI: 2.24, 5.47), alcohol consumption (AOR = 2.48, 95% CI: 1.59, 3.90), and being identified through community-based index case testing (ICT) (AOR = 0.26, 95% CI: 0.13, 0.51) were found to be independent predictors of AHD. Conclusions The prevalence of AHD among newly diagnosed individuals initiating ART was high. PLHIV who consume alcohol should receive detailed counseling on how it can negatively impact their progress with antiretroviral treatment. HIV testing should be enhanced in rural communities by strengthening community health campaigns. Furthermore, community-based index case testing should be strengthened for early identification of PLHIV. …

by Haoran Cui In order to meet the increasing demand of high-performance control in industrial production, a new sliding mode variable structure control algorithm, Asymptotic Sliding Mode Control (ASMC), is designed in this study to solve the serious chattering problem of sliding mode control. Firstly, a traditional sliding mode exponential approximation law control model and a state space and control function are constructed based on sliding mode control. Secondly, by eliminating the jitter factor, ASMC algorithm is combined with sliding mode control to achieve precise control of permanent magnet synchronous motor (PMSM) and improve its performance. The experimental results indicated that in the simulation experiment, the research system tended to stabilize within 0.2–0.3 seconds, and the system chattering was significantly suppressed. And its output was smoother, the jitter amplitude was significantly reduced by 1/3, and the output torque was more stable. In addition, when the parameter H0 changed to 2H0, the overall speed curve did not change much, with only a slight overshoot. The overshoot was only 2.8%, and the change amplitude was maintained at around 25r/min, indicating that the research system had strong self stability performance. In actual experiments, the current command oscillation of the research system was significantly reduced. The local graph showed that the output fluctuation amplitude of the asymptotic approach law actual control was significantly smaller under no-load disturbance. When the H0 changed towards 2H0, the actual adjustment time was about 0.1 seconds, which was consistent with the simulation experiment. Therefore, the contribution of the research is that the ASMC algorithm can suppress the chattering problem of the system and improve the approaching speed, thus improving the speed regulation quality of the system. This new algorithm has great theoretical and practical significance for improving the performance of PMSM, and is practical in the actual vector control system of PMSM.

Infection and Immunity, Ahead of Print.

Abstract Background Over the past years, there has been a growing concern that a considerable amount of anti-malarial supply in the underdeveloped world particularly in the private sector, is of poor quality. The World Health Organization (WHO) has received about 1500 reports that mentions instances of substandard and falsified products since 2013. The majority of the reports concerned antibiotics and anti-malarials. The majority of reports (42%) originate from the WHO African region. Objective This study intends to assess the quality of the most widely used anti-malarial medications [artemether-lumefantrine tablets, chloroquine phosphate tablets, primaquine phosphate tablets, artesunate, and artemether injections] in Gambella, South-West, Ethiopia. Methods A total of 52 samples were collected on June 2022 from Gambella National Regional State, Ethiopia. Half of the districts (six) located in the four zones of the region were chosen using simple random sampling technique. All drug retail outlets available in the selected districts (locally known as woredas) were included. The samples were subjected to visual inspection with a tool adopted from the joint WHO/FIP/ USP checklist. The pharmacopeial tests for identification, uniformity of dosage forms, assay, thickness, diameter, hardness, friability, disintegration test, dissolution, and sterility tests were carried out according to the USP 44-NF 39 and International Pharmacopoeia 11th edition, 2022 monographs. Results and Discussion Only 25% of the samples were registered on the Ethiopian Food and Drug Authority (EFDA’s) electronic regulatory/ registration system (ERIS). Besides, 88.8% of artemether injection products were presented in clear glass ampoules. This might expose the products to photochemical degradation that leads to in loss of anti-plasmodial activity. In addition, 50% of the artemether products assessed were not bioequivalent with the comparator product in the in vitro dissolution comparison tests. Overall, the study findings reveal a high prevalence (58.3%) of substandard anti-malarial drugs in the region. The stated percent of the samples had failed in one or more of the quality test parameters assessed in this study. Conclusion The study findings reveal a high prevalence (58.3%) of substandard anti-malarial drugs in the region. Only a quarter were registered and 38% of the unregistered products failed the quality tests. Hence, the national, regional medicine regulatory bodies and other stake holders should perform the required roles to circumvent presence of Substandard and Falsified (SF) anti-malarial drugs in the study sites. …

Abstract Background A quasi-experimental comparative trial will be designed in Burkina Faso. The study will compare the use and preferences for two groups types of insecticide-treated nets textile: polyester-based and polyethylene-based, according to their use and preferences in selected health districts. These health districts will be selected in three eco-climate zones (Sahelian, dry savannah and wet savannah) in the country. These findings will inform decisions on future net procurements for national malaria control programme in 2025. Methods Quantitative surveys and qualitative data collection will be carried out to gather information on the type of net textile most commonly used and preferred by the community. They will be performed between the end of the dry season and the early rainy season. The quantitative surveys involved household interviews with households and individuals’ questionnaires, while the qualitative data collection involved in-depth individual interviews and focus group discussions to explore and clarify some key evaluation criteria. A total of 9450 insecticide-treated nets were surveyed for quantitative survey purposes. For the qualitative study, 48 in-depth individual interviews and 12 focus group discussions were carried out. A mixed model approach combining the results from quantitative surveys and qualitative studies will be used for decision-making on the type of insecticide-treated net preference. Conclusion This methodological approach will be used by the National Malaria Control Programme to conduct this study on determinants of net use in Burkina Faso in order to provide robust evidence across diverse settings. This mixed-methods approach for data collection and analysis could be used in other countries to provide evidence that would help to increase the uptake of insecticide-treated nets, the main vector control tool in Africa. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

A 4-year-old child with sickle cell disease was transferred from the local health center to the emergency department (ED) due to fever, lethargy, jaundice, vomiting and severe anemia. His symptoms had been progressive over five days. The patient lived in a rural part of the Sultanate of Oman, and enjoyed accompanying his grandmother while she tended to her goats, some of which had given birth recently. The child also had occasional tick and mosquito bites, but no history of travel. He had multiple previous admissions for vaso-occlusive crises and was receiving hydroxyurea.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 6, Page 834-837, September 15, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 6, Page 847-849, September 15, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 6, Page 849-850, September 15, 2024.