Effectiveness of a community health worker-led low-sodium salt intervention to reduce blood pressure in rural Bangladesh: protocol for a cluster randomized controlled trial.

BACKGROUND: High blood pressure is a major public health problem in low- and middle-income countries. Low-sodium salt substitute (LSSS) is a promising population-level blood pressure-lowering intervention requiring minimal behavioral change. The optimal method of delivering LSSS to individuals, however, is currently unknown. Community health workers (CHWs) have successfully been used to implement health interventions in Bangladesh and may provide a venue for the dissemination of LSSS. METHODS: We aim to conduct a cluster-randomized controlled trial involving 309 households in rural Bangladesh previously identified and characterized by the BRAC James P Grant School of Public Health, BRAC University (BRAC JPGSPH). These households will be randomly assigned to three arms: (1) control, i.e., no intervention; (2) information only, i.e., community health workers will provide basic information on high blood pressure, the health consequences of excessive salt consumption, and feedback to the participant on the likely quantity of salt s/he consumes (estimated using a questionnaire); (3) free LSSS arm: the same information as in arm 2 will be provided, but participants will receive 6 months of free low-sodium salt along with education on the benefits of LSSS. One male and one female adult (age ≥ 18 years) in each household will be invited to participate, the exclusion criteria being households with members known to have high serum potassium levels, are taking medications known to elevate potassium levels (e.g., ACE inhibitors, ARBs, potassium-sparing diuretics), are already taking potassium supplements, or those who have known kidney disease or abnormal serum creatinine at baseline. The primary endpoint will be blood pressure at 6 months post-intervention. DISCUSSION: Recent large clinical trials of LSSS in China and India have shown not only blood pressure improvements, but also stroke, major cardiac event, and all-cause mortality reductions. Nevertheless, how to best translate this intervention to population-level effectiveness remains unclear. Our study would test whether a community health worker-based program could be effectively used to disseminate LSSS and achieve measurable blood pressure benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT05425030. Registered on June 21, 2022.

The role of Covid-19 outbreak on well-being of healthcare employees of Turkey by considering gender differences.

In this paper, we explore the role of the Covid-19 outbreak on the well-being of healthcare employees (HE) in Turkey by adopting a survey method with 680 (188 men and 492 women) participants. Our results indicate that both the outbreak negatively affects the well-being of HE, and women face more levels of fear, negative feelings and violence than men. Within the context of this research, we contribute to the literature by considering the changing living conditions in the outbreak and adopting a comprehensive approach to reveal sub-level of well-being as subjective and psychological well-being rather than focusing on only mental health like previous studies.

N-acetyl-L-cysteine treatment reduces beta-cell oxidative stress and pancreatic stellate cell activity in a high fat diet-induced diabetic mouse model.

Obesity plays a major role in type II diabetes (T2DM) progression because it applies metabolic and oxidative stress resulting in dysfunctional beta-cells and activation of intra-islet pancreatic stellate cells (PaSCs) which cause islet fibrosis. Administration of antioxidant N-acetyl-L-cysteine (NAC) in vivo improves metabolic outcomes in diet-induced obese diabetic mice, and in vitro inhibits PaSCs activation. However, the effects of NAC on diabetic islets in vivo are unknown. This study examined if dosage and length of NAC treatment in HFD-induced diabetic mice effect metabolic outcomes associated with maintaining healthy beta-cells and quiescent PaSCs, in vivo. Male C57BL/6N mice were fed normal chow (ND) or high-fat (HFD) diet up to 30 weeks. NAC was administered in drinking water to HFD mice in preventative treatment (HFDpNAC) for 23 weeks or intervention treatment for 10 (HFDiNAC) or 18 (HFDiNAC+) weeks, respectively. HFDpNAC and HFDiNAC+, but not HFDiNAC, mice showed significantly improved glucose tolerance and insulin sensitivity. Hyperinsulinemia led by beta-cell overcompensation in HFD mice was significantly rescued in NAC treated mice. A reduction of beta-cell nuclear Pdx-1 localization in HFD mice was significantly improved in NAC treated islets along with significantly reduced beta-cell oxidative stress. HFD-induced intra-islet PaSCs activation, labeled by αSMA, was significantly diminished in NAC treated mice along with lesser intra-islet collagen deposition. This study determined that efficiency of NAC treatment is beneficial at maintaining healthy beta-cells and quiescent intra-islet PaSCs in HFD-induced obese T2DM mouse model. These findings highlight an adjuvant therapeutic potential in NAC for controlling T2DM progression in humans.

Peste des petits ruminants virus antibodies in domestic large ruminants in Bangladesh.

INTRODUCTION: Peste des petits ruminants (PPR) is an important transboundary animal disease of small ruminants which causes serious damage to the livelihood and food security of millions of small-scale farmers. PPR is endemic in goats in Bangladesh since 1993. The aim of this study was to determine the seroprevalence of PPR in sheep, cattle, and buffaloes in Bangladesh. METHODOLOGY: A total of 434 blood samples from sheep (n = 100), cattle (n = 190) and buffalo (n = 144) were collected aseptically. Sera were separated and antibody titer was determined using a commercially available c-ELISA kit. RESULTS: The overall seroprevalence was 16% and 3.68% in sheep and cattle, respectively, while buffaloes had a considerably higher seroprevalence of 42.36%. The study suggests that buffaloes are more prone to the PPR virus (PPRV) infection and cattle. CONCLUSIONS: This study provides serological evidence of PPRV infection in cattle and buffaloes. These results may warrant further studies to find out the role of large ruminants in transmitting PPRV infection to small ruminants and vice versa and inclusion of all domestic and wild ruminants for regular surveillance program.

Gut bacterial gene changes following pegaspargase treatment in pediatric patients with acute lymphoblastic leukemia.

Treatment of pediatric acute lymphoblastic leukemia (ALL) with pegaspargase exploits ALL cells dependency on asparagine. Pegaspargase depletes asparagine, consequentially affecting aspartate, glutamine and glutamate. The gut as a confounding source of these amino acids (AAs) and the role of gut microbiome metabolism of AAs has not been examined. We examined asparagine, aspartate, glutamine and glutamate in stool samples from patients over pegaspargase treatment. Microbial gene-products, which interact with these AAs were identified. Stool asparagine declined significantly, and 31 microbial genes changed over treatment. Changes were complex, and included genes involved in AA metabolism, nutrient sensing, and pathways increased in cancers. While we identified changes in a gene (iaaA) with limited asparaginase activity, it lacked significance after correction leaving open other mechanisms for asparagine decline, possibly including loss from gut to blood. Understanding pathways that change AA availability, including by microbes in the gut, could be useful in optimizing pegaspargase therapy.

Beam characteristics of the first clinical 360° rotational single gantry room scanning pencil beam proton treatment system and comparisons against a multi-room system.

PURPOSE: The purpose of this study was to present the proton beam characteristics of the first clinical single-room ProBeam Compact™ proton therapy system (SRPT) and comparison against multi-room ProBeam™ system (MRPT). MATERIALS AND METHODS: A newly designed SRPT with proton beam energies ranging from 70 to 220 MeV was commissioned in late 2019. Integrated depth doses (IDDs) were scanned using 81.6 mm diameter Bragg peak chambers and normalized by outputs at 15 mm WET and 1.1 RBE offset, following the methodology of TRS 398. The in-air beam spot profiles were acquired by a planar scintillation device, respectively, at ISO, upper and down streams, fitted with single Gaussian distribution for beam modeling in Eclipse v15.6. The field size effect was adjusted for the best overall accuracy of clinically relevant field QAs. The halo effects at near surface were quantified by a pinpoint ionization chamber. Its major dosimetric characteristics were compared against MRPT comparable beam dataset. RESULTS: Contrast to MRPT, an increased proton straggling in the Bragg peak region was found with widened beam distal falloffs and elevated proximal transmission dose values. Integrated depth doses showed 0.105-0.221 MeV (energy sigma) or 0.30-0.94 mm broader Bragg peak widths (Rb80 -Ra80 ) for 130 MeV or higher energy beams and up to 0.48-0.79 mm extended distal falloffs (Rb20 -Rb80 ). Minor differences were identified in beam spot sizes, spot divergences, proton particles/MU, and field size output effects. High passing scores are reported for independent end-to-end dosimetry checks by IROC and for initial 108 field-specific QAs at 3%/3 mm Gamma index with fields regardless with or without range shifters. CONCLUSIONS: The author highlighted the dosimetry differences in IDDs mainly caused by the shortened beam transport system of SRPT, for which new acceptance criteria were adapted. This report offers a unique reference for future commissioning, beam modeling, planning, and analysis of QA and clinical studies.

Opinion: Are Organoids the End of Model Evolution for Studying Host Intestinal Epithelium/Microbe Interactions?

In the pursuit to understand intestinal epithelial cell biology in health and disease, researchers have established various model systems, from whole animals (typically rodents) with experimentally induced disease to transformed human carcinomas. The obvious limitation to the ex vivo or in vitro cell systems was enriching, maintaining, and expanding differentiated intestinal epithelial cell types. The popular concession was human and rodent transformed cells of mainly undifferentiated cells, with a few select lines differentiating along the path to becoming goblet cells. Paneth cells, in particular, remained unculturable. The breakthrough came in the last decade with the report of conditions to grow mouse intestinal organoids. Organoids are 3-dimensional ex vivo "mini-organs" of the organ from which the stem cells were derived. Intestinal organoids contain fully differentiated epithelial cells in the same spatial organization as in the native epithelium. The cells are suitably polarized and produce and secrete mucus onto the apical surface. This review introduces intestinal organoids and provide some thoughts on strengths and weaknesses in the application of organoids to further advance our understanding of the intestinal epithelial-microbe relationship.

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆.

S100A10 (p11), a member of the S100 family of small dimeric EF-hand-type Ca2+-binding proteins, plays a role in a variety of both intracellular and extracellular processes. Previous studies have suggested that p11 is intrinsically unstable and requires binding to annexin A2 (p36) to prevent its rapid ubiquitylation and degradation. Our laboratory has shown that p11 levels are stimulated by the expression of the oncoprotein, PML/RARα. Furthermore, treatment of the APL cell line, NB4 with all-trans retinoic acid (ATRA) causes the rapid loss of p36 and p11 protein. However, the mechanism by which ATRA regulates p11 levels has not been established. Here, we show that the proteasomal inhibitor, lactacystin reversed the ATRA-dependent loss of p11, but did not cause an accumulation of ubiquitylated forms of p11, suggesting that ATRA promotes the proteasomal degradation of p11 in an ubiquitin-independent manner. ATRA treatment of MCF-7 breast cancer cells reduced p11 but not p36 transcript and protein levels, thus indicating that ATRA can regulate p11 levels independently of PML/RARα and p36. Overexpression of p36 upregulated p11 protein but not mRNA levels, indicating that p36 affects p11 post translationally. The forced expression of ubiquitin and p11 in 293 T cells resulted in ubiquitylation of p11 that was blocked by mutagenesis of lysine 57. This study highlights the complex regulation of p11 by retinoid signaling and challenges the hypothesis that ubiquitin-mediated proteasomal degradation of p11 represents a universal mechanism of regulation of this protein.

Dried fluid spots for peste des petits ruminants virus load evaluation allowing for non-invasive diagnosis and genotyping.

BACKGROUND: Active surveillance of peste des petits ruminants (PPR) should ease prevention and control of this disease widely present across Africa, Middle East, central and southern Asia. PPR is now present in Turkey at the gateway to the European Union. In Bangladesh, the diagnosis and genotyping of PPR virus (PPRV) may be hampered by inadequate infrastructures and by lack of proper clinical material, which is often not preserved under cold chain up to laboratories. It has been shown previously that Whatman® 3MM filter paper (GE Healthcare, France) preserves the nucleic acid of PPRV for at least 3 months at 32°C. RESULTS: In this study, we demonstrate the performances of filter papers for archiving RNA from local PPRV field isolates for further molecular detection and genotyping of PPRV, at -70°C combined with ambient temperature, for periods up to 16 months. PPR-suspected live animals were sampled and their blood and nasal swabs were applied on filter papers then air dried. Immediately after field sampling, RT-PCR amplifying a 448-bp fragment of the F gene appeared positive for both blood and nasal swabs when animals were in febrile stage and only nasal swabs were detected positive in non-febrile stage. Those tested positive were monitored by RT-PCR up to 10 months by storage at -70°C. At 16 months, using real time RT-PCR adapted to amplify the N gene from filter paper, high viral loads could still be detected (~2 x 10(7) copy numbers), essentially from nasal samples. The material was successfully sequenced and a Bayesian phylogenetic reconstruction achieved adequate resolution to establish temporal relationships within or between the geographical clusters of the PPRV strains. CONCLUSIONS: This clearly reveals the excellent capacity of filter papers to store genetic material that can be sampled using a non-invasive approach.

Efficacy of combined chloroquine and sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria in Bangladesh.

A study of the therapeutic efficacy of combined chloroquine and sulfadoxine-pyrimethamine (SP) for the treatment of uncomplicated Plasmodium falciparum malaria was carried out from June to November 2002, using the standard protocol recommended by the WHO for a low-to-moderate transmission area, in two sentinel sites in Bangladesh: Alikadam Upazilla in Bandarban district and Matiranga Upazilla in Khagrachari district. A total of 133 patients was followed-up to 28 d. Total failure rates were 25.9 and 30.7% in Alikadam and Matiranga, respectively. No severe side effects due to the drugs were encountered during the study period. Chloroquine and SP is not a suitable combination for the first-line treatment of P. falciparum in Bangladesh.