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The advent of the COVID-19 vaccine signified a historic milestone in the field of vaccinology, showcasing remarkable scientific collaboration and global solidarity. However, the most prominent hurdle in maximizing the global public health impact of vaccines remains the absence of comprehensive and inclusive health systems in both high- and low-resource settings. Our discussion centers around the major contributing factors that played a key role in formulating the rapid and efficacious COVID-19 vaccines. Simultaneously, we illuminate the disparities that have marred the vaccine delivery process throughout the pandemic. In particular, we highlight the case scenarios of two minority and vulnerable communities from the Global South and North—the undocumented migrants in Thailand and the Roma community in Europe—who continue to experience inequitable vaccine access regardless of their location. We note that a crucial programmatic solution that is rooted in inclusive and equitable global public health policy, characterized by empathy and trust and bolstered by digital innovation, is lacking. These examples underscore the significance of establishing a comprehensive and integrated health system at multiple levels across countries and the entire world. Furthermore, we highlight the need for both local and global actors to collaboratively engage in vaccine distribution efforts. By gaining a concise grasp of these intricacies, the global community will be better poised to effectively combat future pandemics and emerging health challenges. [ABSTRACT FROM AUTHOR]

We show how to apply renormalization group algorithms incorporating entanglement filtering methods and a loop optimization to a tensor network which includes Grassmann variables which represent fermions in an underlying lattice field theory. As a numerical test a variety of quantities are calculated for two dimensional Wilson-Majorana fermions and for the two flavor Gross-Neveu model. The improved algorithms show much better accuracy for quantities such as the free energy and the determination of Fisher’s zeros. [ABSTRACT FROM AUTHOR]

AbstractThe 2030 Sustainable Development Goals include persons with disabilities in various elements related to education, employment, equality, and accessibility of human settlements. As this group constitutes a significant share of the population in Myanmar, the government recognises the importance of promoting their rights and ensuring their inclusion in the country’s development agenda. However, they often encounter social and institutional exclusions, including restricted access to basic social protection services. The COVID-19 pandemic and military coup in 2021 have further exacerbated existing precarious situations with minimal investment in welfare improvement. The objective of our study was to determine the effect of the COVID-19 pandemic and military coup on the well-being and social security of persons with disabilities in Myanmar. By analysing prevailing policy documents, our research provides recommendations for enhancing policies for persons with disabilities, particularly during periods of humanitarian crisis and ongoing conflicts in Myanmar and other countries. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human exposure to intensively farmed livestock is a potential risk for transmission of antibiotic-resistant bacteria (ARB) but few studies have assessed the relative role of animal vs. environmental sources of ARB in low-resource community settings. OBJECTIVES: We conducted an observational study to compare ARB colonization and antibiotic-resistant gene prevalence and abundance in humans with high or low exposure to poultry in rural households, commercial poultry farms, and urban markets in Bangladesh. METHODS: Extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant E. coli were quantified in feces from adults with high or low poultry exposure (푛 = 100, respectively), poultry (푛 = 200), drinking water (푛 = 120), and wastewater (푛 = 120) from 40 rural households, 40 poultry farms, and 40 urban markets. RESULTS: ESBL-producing E. coli (ESBL-EC) prevalence was 67.5% (95% CI: 61.0, 74.0) in samples from adults, 68.0% (95% CI: 61.5, 74.5) in samples from poultry, and 92.5% (95% CI: 87.7, 97.3) in wastewater samples. Carbapenem-resistant E. coli prevalence was high in market wastewaters [30% (95% CI: 15.0, 45.0)] but low in humans (1%) and poultry (1%). Human, poultry, and wastewater isolates shared common resistance genes: 푏푙푎CTX-M-1, 푞푛푟, and 푏푙푎TEM. Human colonization was not significantly associated with exposure to poultry or setting (rural, farm, or market). Ninety-five percent of commercial poultry farms routinely administered antibiotics. Susceptibility tests were significantly different in household vs. farm and market poultry isolates for four of seven antibiotic classes. In human isolates, there were no differences except aminoglycoside resistance (16.4% high vs. 4.4% low exposure, 푝=0.02). Urban market wastewaters and poultry samples had significantly higher concentrations of ESBL-EC (푝<0.001) and 푏푙푎CTX-M-1 (푝<0.001) compared with samples from farms and rural households. DISCUSSION: ESBL-EC colonization was high in humans but not significantly associated with exposure to poultry. Bidirectional transmission of antibiotic resistance is likely between humans, poultry, and the environment in these community settings, underlining the importance of One Health mitigation strategies. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract E-cadherin transcriptional activator EP300 is down-regulated in metaplastic breast carcinoma, a rare form of triple negative and E-cadherin-negative aggressive breast cancer with a poor clinical outcome. In order to shed light on the regulation of E-cadherin by EP300 in breast cancer we analyzed by immunohistochemistry 41 cases of invasive breast cancer with both E-cadherinhigh and E-cadherinlow expression levels, together with 20 non-malignant breast tissues. EP300 and E-cadherin showed a positive correlation in both non-malignant and cancer cases and both markers together were better predictors of lymph node metastasis than E-cadherin alone. These data support a metastasis suppressor role for EP300 in breast cancer. However, some reports suggest an oncogenic role for EP300. We generated a breast cancer cell model to study E-cadherin-independent effects of EP300 by over-expression of EP300 in HS578T cells which have E-cadherin promoter hypermethylated. In this cell system, EP300 led to up-regulation of mesenchymal (vimentin, Snail, Slug, Zeb1) and stemness (ALDH+ and CD44high/CD24low) markers, increases in migration, invasion, anchorage-independent growth and drug resistance. Genome-wide expression profiling identified aldo-keto reductases AKR1C1-3 as effectors of stemness and drug resistance, since their pharmacological inhibition with flufenamic acid restored both doxorubicin and paclitaxel sensitivity and diminished mammosphere formation. Thus, in cells with a permissive E-cadherin promoter, EP300 acts as a tumour/metastasis supressor by up-regulating E-cadherin expression, maintenance of the epithelial phenotype and avoidance of an epithelial-to-mesenchymal transition. In cells in which the E-cadherin promoter is hypermethylated, EP300 functions as an oncogene via up-regulation of aldo-keto reductases. This offers the rationale of using current aldo-keto reductase inhibitors in breast cancer treatment. [ABSTRACT FROM AUTHOR]

Code completion helps developers use application programming interfaces (APIs) and frees them from remembering every detail. In this paper, we first describe a novel technique called Context-sensitive Code Completion (CSCC) for improving the performance of API method call completion. CSCC is context sensitive in that it uses new sources of information as the context of a target method call. CSCC indexes method calls in code examples by their context. To recommend completion proposals, CSCC ranks candidate methods by the similarities between their contexts and the context of the target call. Evaluation using a set of subject systems and five popular state-of-the-art techniques suggests that CSCC performs better than existing type or example-based code completion systems. We conduct experiments to find how different contextual elements of the target call benefit CSCC. Next, we investigate the adaptability of the technique to support another form of code completion, i.e., field completion. Evaluation with eight different subject systems suggests that CSCC can easily support field completion with high accuracy. Finally, we compare CSCC with four popular statistical language models that support code completion. Results of statistical tests from our study suggest that CSCC not only outperforms those techniques that are based on token level language models, but also in most cases performs better or equally well with GraLan, the state-of-the-art graph-based language model. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a leading cause of hospitalization and death worldwide. Heavy metals such as arsenic have been shown to drive co-selection of antibiotic resistance, suggesting arsenic-contaminated drinking water is a risk factor for antibiotic resistance carriage. This study aimed to determine the prevalence and abundance of antibiotic-resistant Escherichia coli (AR-Ec) among people and drinking water in high (Hajiganj, >100 μg/L) and low arsenic-contaminated (Matlab, <20 μg/L) areas in Bangladesh. Drinking water and stool from mothers and their children (<1 year) were collected from 50 households per area. AR-Ec was detected via selective culture plating and isolates were tested for antibiotic resistance, arsenic resistance, and diarrheagenic genes by PCR. Whole-genome sequencing (WGS) analysis was done for 30 E. coli isolates from 10 households. Prevalence of AR-Ec was significantly higher in water in Hajiganj (48%) compared to water in Matlab (22%, p <0.05) and among children in Hajiganj (94%) compared to children in Matlab (76%, p <0.05), but not among mothers. A significantly higher proportion of E. coli isolates from Hajiganj were multidrug-resistant (83%) compared to isolates from Matlab (71%, p <0.05). Co-resistance to arsenic and multiple antibiotics (MAR index >0.2) was observed in a higher proportion of water (78%) and child stool (100%) isolates in Hajiganj than in water (57%) and children (89%) in Matlab (p <0.05). The odds of arsenic-resistant bacteria being resistant to third-generation cephalosporin antibiotics were higher compared to arsenic-sensitive bacteria (odds ratios, OR 1.2–7.0, p <0.01). WGS-based phylogenetic analysis of E. coli isolates did not reveal any clustering based on arsenic exposure and no significant difference in resistome was found among the isolates between the two areas. The positive association detected between arsenic exposure and antibiotic resistance carriage among children in arsenic-affected areas in Bangladesh is an important public health concern that warrants redoubling efforts to reduce arsenic exposure. Author summary: Antibiotic resistance is one of the leading causes of death and hospitalization worldwide. While the major drivers of antibiotic resistance are the overuse and misuse of antibiotics, natural elements such as heavy metals can also promote antibiotic resistance. In this observational study, we investigated the prevalence and abundance of antibiotic-resistant bacteria in drinking water samples and among mothers and children from the same households in two rural areas of Bangladesh with high and low levels of arsenic contamination in drinking water. We found that the prevalence of antibiotic-resistant E. coli was significantly higher in water and among children in high arsenic-contaminated areas compared to the low arsenic-contaminated areas. We also found that a higher proportion of E. coli isolates from the high arsenic area were resistant to multiple antibiotics including penicillin, cephalosporin, and chloramphenicol. Arsenic-resistant bacteria are more likely to be resistant to certain groups of antibiotics, including third-generation cephalosporins. Overall, this study suggests that arsenic exposure could be an important risk factor for the carriage of antibiotic-resistant organisms which needs to be taken into consideration when designing community-based interventions to combat antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The article presents a clinical study on the medical role played by blood platelets in the neutrophils regulation infiltration. It notes that sepsis is considered to be the major cause of death in the intensive care units. After the conducted analysis and tests, it was proven that platelets provide regulation of neutrophil recruitment to the lung.

Background and Purpose: Neutrophil-mediated lung injury is an insidious feature in sepsis although the mechanisms regulating pulmonary recruitment of neutrophils remain elusive. Here, we investigated the role of P-selectin glycoprotein-ligand-1 (PSGL-1) in sepsis-induced neutrophil recruitment and tissue injury in the lung.Experimental Approach: Bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, oedema formation and CXC chemokines were determined 24 h after caecal ligation and puncture (CLP) in mice. Animals were pretreated with a control antibody, monoclonal antibodies directed against PSGL-1 and P-selectin as well as a platelet-depleting antibody directed against GP1balpha.Key Results: CLP caused pulmonary damage characterized by oedema formation, neutrophil infiltration and increased levels of CXC chemokines in the lung. Immunoneutralization of PSGL-1 or P-selectin reduced CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 56% and lung myeloperoxidase activity by 62%. Notably, the inhibitory effect of the anti-PSGL-1 antibody on sepsis-induced neutrophil infiltration was also observed in platelet-depleted mice. Moreover, inhibition of PSGL-1 and P-selectin abolished CLP-induced oedema formation and tissue damage in the lung. CLP-induced formation of CXC chemokines was not changed in mice pretreated with the anti-PSGL-1 and anti-P-selectin antibodies.Conclusions and Implications: These data demonstrate that PSGL-1 plays a key role in pulmonary infiltration of neutrophils as well as lung oedema associated with abdominal sepsis. Moreover, our findings suggest that PSGL-1-dependent neutrophil recruitment is independent of circulating platelets. Thus, these novel findings indicate that PSGL-1 may be a useful target to protect against sepsis-induced accumulation of neutrophils and tissue damage in the lung. [ABSTRACT FROM AUTHOR]

The article presents a study that aims to define the role of p38 mitogen-activated protein kinase (MAPK) signaling in septic lung injury. It indicated that p38 MAPK signaling establishes a key role in determining CXC chemokine production in septic lung injury. The study also revealed that inhibition of p38 MAPK activity gets rid of pulmonary infiltration of leukocytes as well as lung edema.

The rapid growth of the elderly population is a major global demographic and social issue. Unfortunately, there is a shortage of pension plans and social security programmes for this population in developing countries, which has severe consequences for their quality of life and well-being. In this article, we aim to better understand the pension systems in developing country contexts such as Ghana, Pakistan, and Myanmar by reviewing official government materials (for example, pension reports) and the published literature to suggest relevant policy recommendations. We observed several policy implementation gaps and inequities in pension schemes for older people, specifically for informal and private sector workers. Considering the size of formal versus informal economies and the level of development index of each country, we suggest a wide variety of options for pension policies, financing, designing cash benefits, and pension payments to cover all older citizens. This article addresses the unmet needs of the elderly and their wider economic sustainability to ensure social justice and resource utilisation. Governments in developing countries should embrace and establish unique, inclusive, and friendly policies encompassing the informal sector to warrant older adults' functional and social well-being with dignity and honour. [ABSTRACT FROM AUTHOR]

Antiprotozoal drug nitazoxanide (NTZ) has shown diverse pharmacological properties and has appeared in several clinical trials. Herein we present the synthesis, characterization, in vitro biological investigation, and in silico study of four hetero aryl amide analogs of NTZ. Among the synthesized molecules, compound 2 and compound 4 exhibited promising antibacterial activity against Escherichia coli (E. coli), superior to that displayed by the parent drug nitazoxanide as revealed from the in vitro antibacterial assay. Compound 2 displayed zone of inhibition of 20 mm, twice as large as the parent drug NTZ (10 mm) in their least concentration (12.5 µg/ml). Compound 1 also showed antibacterial effect similar to that of nitazoxanide. The analogs were also tested for in vitro cytotoxic activity by employing cell counting kit‐8 (CCK‐8) assay technique in HeLa cell line, and compound 2 was identified as a potential anticancer agent having IC50 value of 172 µg which proves it to be more potent than nitazoxanide (IC50 = 428 µg). Furthermore, the compounds were subjected to molecular docking study against various bacterial and cancer signaling proteins. The in vitro test results corroborated with the in silico docking study as compound 2 and compound 4 had comparatively stronger binding affinity against the proteins and showed a higher docking score than nitazoxanide toward human mitogen‐activated protein kinase (MAPK9) and fatty acid biosynthesis enzyme (FabH) of E. coli. Moreover, the docking study demonstrated dihydrofolate reductase (DHFR) and thymidylate synthase (TS) as probable new targets for nitazoxanide and its synthetic analogs. Overall, the study suggests that nitazoxanide and its analogs can be a potential lead compound in the drug development. [ABSTRACT FROM AUTHOR]

The term 'vitamin C' describes a group of compounds with antiscorbutic activity of l -ascorbic acid (AA). Despite AA's omnipresence in plant-derived foods, its derivatives have also been successfully implemented in the food industry as antioxidants, including the D-isomers, which lack vitamin C activity. This study aimed to determine the relationship between redox-related activities for five derivatives of AA using electrochemical, chemical, and biological approaches. Here we report that AA, C-vitamers, and other commonly consumed AA derivatives differ in their redox-related activities. As long as the physiological range of concentrations was maintained, there was no simple relationship between their redox properties and biological activity. Clear distinctions in antioxidant activity were observed mostly at high concentrations, which were strongly correlated with electrochemical and kinetic parameters describing redox-related properties of the studied compounds. Despite obvious similarities in chemical structures and antioxidant activity, we showed that C-vitamers may exhibit different nutrigenomic effects. Together, our findings provide a deeper insight into so far underinvestigated area combining chemical properties with biological activities of commonly applied AA derivatives. [Display omitted] • Electrochemical parameters were strongly correlated with redox reaction kinetics. • Distinct CAA was revealed only at 500–1000 μM concentrations of AA derivatives. • Chemical properties were strongly correlated with CAA at 200–500 μM concentrations. • CaA was the most powerful antioxidant among AA derivatives. • AA and CaA exhibited different nutrigenomic effects. [ABSTRACT FROM AUTHOR]

The originally published, uncorrected article and the republished, corrected article are provided here for reference. This article was republished on September 12, 2023 to add Yushuf Sharker as the eighth author. [Extracted from the article]

Urinary tract infection (UTI) accounts for a significant morbidity and mortality across the world and is a leading cause for antibiotic prescriptions in the community especially in developing countries. Empirical choice of antibiotics for treatment of UTI is often discordant with the drug susceptibility of the etiologic agent. This study aimed to estimate the prevalence of community-acquired UTI caused by antibiotic resistant organisms. This was a cross-sectional study where urine samples were prospectively collected from 4,500 patients at the icddr,b diagnostic clinic in Dhaka, Bangladesh during 2016–2018. Urine samples were analyzed by standard culture method and the isolated bacteria were tested for antibiotic susceptibility by using disc diffusion method and VITEK-2. Descriptive statistics were used to estimate the prevalence of community acquired UTI (CA-UTI) by different age groups, sex, and etiology of infection. Relationship between the etiology of CA-UTI and age and sex of patients was analyzed using binary logistic regression analysis. Seasonal trends in the prevalence of CA-UTI, multi-drug resistant (MDR) pathogens and MDR Escherichia coli were also analyzed. Around 81% of patients were adults (≥18y). Of 3,200 (71%) urine samples with bacterial growth, 920 (29%) had a bacterial count of ≥1.0x105 CFU/ml indicating UTI. Women were more likely to have UTI compared to males (OR: 1.48, CI: 1.24–1.76). E. coli (51.6%) was the predominant causative pathogen followed by Streptococcus spp. (15.7%), Klebsiella spp. (12.1%), Enterococcus spp. (6.4%), Pseudomonas spp. (4.4%), coagulase-negative Staphylococcus spp. (2.0%), and other pathogens (7.8%). Both E. coli and Klebsiella spp. were predominantly resistant to penicillin (85%, 95%, respectively) followed by macrolide (70%, 76%), third-generation cephalosporins (69%, 58%), fluoroquinolones (69%, 53%) and carbapenem (5%, 9%). Around 65% of patients tested positive for multi-drug resistant (MDR) uropathogens. A higher number of male patients tested positive for MDR pathogens compared to the female patients (p = 0.015). Overall, 71% of Gram-negative and 46% of Gram-positive bacteria were MDR. The burden of community-acquired UTI caused by MDR organisms was high among the study population. The findings of the study will guide clinicians to be more selective about their antibiotic choice for empirical treatment of UTI and alleviate misuse/overuse of antibiotics in the community. [ABSTRACT FROM AUTHOR]

Breast cancer has historically been one of the leading causes of death for women worldwide. As of 2020, breast cancer was reported to have overtaken lung cancer as the most common type of cancer globally, representing an estimated 11.3% of all cancer diagnoses. A multidisciplinary approach is taken for the diagnosis and treatment of breast cancer that includes conventional and targeted treatments. However, current therapeutic approaches to treating breast cancer have limitations, necessitating the search for new treatment options. Cancer cells require adequate iron for their continuous and rapid proliferation. Excess iron saturates the iron-binding capacity of transferrin, resulting in non-transferrin-bound iron (NTBI) that can catalyze free-radical reactions and may lead to oxidant-mediated breast carcinogenesis. Moreover, excess iron and the disruption of iron metabolism by local estrogen in the breast leads to the generation of reactive oxygen species (ROS). Therefore, iron concentration reduction using an iron chelator can be a novel therapeutic strategy for countering breast cancer development and progression. This review focuses on the use of iron chelators to deplete iron levels in tumor cells, specifically in the breast, thereby preventing the generation of free radicals. The inhibition of DNA synthesis and promotion of cancer cell apoptosis are the targets of breast cancer treatment, which can be achieved by restricting the iron environment in the body. We hypothesize that the usage of iron chelators has the therapeutic potential to control intracellular iron levels and inhibit the breast tumor growth. In clinical settings, iron chelators can be used to reduce cancer cell growth and thus reduce the morbidity and mortality in breast cancer patients. [ABSTRACT FROM AUTHOR]

Many previous studies have reported that smoking behavior is associated with a number of psychological variables. The present study examined whether smoking behavior of Bangladeshi adults can be predicted from their emotional intelligence, perceived stress, and self-esteem. A self-report questionnaire package comprising of Personal Information Form, Emotional Intelligence Scale, Perceived Stress Scale, and Self-Esteem Scale was administered on a purposive sample of 210, nineteenthrough 45-year-old males distributed equally to smoking and non-smoking groups to collect data. Pearson Point Biserial Correlation and Binary Logistic Regression were performed to analyze the data. The results of correlation analyses revealed that smoking behavior of the respondents was negatively associated with emotional intelligence and self-esteem and positively with perceived stress. The results of regression analysis revealed that perceived stress and self-esteem can independently and significantly predict smoking behavior of the respondents. These findings can be taken to suggest that antismoking policies should incorporate, among others, strategies for enhancing emotional intelligence, managing stress, and fostering self-esteem of individuals to help prevent or stop their smoking behavior which is the gateway to further addictive behaviors. [ABSTRACT FROM AUTHOR]

In vivo-induced antigen technology is a method to identify proteins expressed by pathogenic bacteria during human infection. Sera from 10 patients convalescing from cholera infection in Bangladesh were pooled, adsorbed against in vitro-grown El Tor Vibrio cholerae O1, and used to probe a genomic expression library in Escherichia coli constructed from El Tor V. cholerae O1 strain N16961. We identified 38 positive clones in the screen, encoding pill (PilA and TcpA), cell membrane proteins (PilQ, MshO, MshP, and CapK), methyl-accepting chemotaxis proteins, chemotaxis and motility proteins (CheA and CheR), a quorum-sensing protein (LuxP), and four hypothetical proteins. Analysis of immune responses to purified PilA and TcpA in individual patients demonstrated that the majority seroconverted to these proteins, confirming results with pooled sera. These results suggest that PilA and its outer membrane secretin, PilQ, are expressed during human infection and may be involved in colonization of the gastrointestinal tract. These results also demonstrate substantial immune responses to TcpA in patients infected with El Tor V. cholerae O1. In vivo-induced antigen technology provides a simple method for identifying microbial proteins expressed during human infection, but not during in vitro growth. [ABSTRACT FROM AUTHOR]

Background and Aim: Salmonella typhi infection occurs in most endemic areas. Patients suspected of typhoid fever located in the Badda and Shantinagar localities of Dhaka were the studied population. A total of 107 blood specimens were collected. Objective: This study attempted to determine the antibiotic susceptibility pattern of Salmonella typhi among different age and gender groups having clinical symptoms of typhoid fever. Methods: The microorganisms obtained from blood specimens were identified by phenotypical and biochemical tests following standard protocols. Antibiotic susceptibility test was done by the Agar-disc-diffusion method to understand antibiotic susceptibility of the isolates. All the Salmonella typhi isolates were serologically confirmed using a commercial antisera kit. Results and Conclusion: Out of 107, 74 Salmonella typhi isolates showed multidrug-resistant properties. Nalidixic acid, ampicillin, azithromycin, and ciprofloxacin showed high antibiotic resistance percentage. On the other hand meropenem, amikacin, gentamycin showed low antibiotic resistance. Age and sex groups also revealed significant attributes to the multidrug-resistant isolates. Multidrug-resistant pattern of the clinical isolates of Salmonella typhi of the current study has presented a matter of great public health concern in Dhaka city, Bangladesh. The first line of antibiotics can be prescribed, taking into consideration of age and gender. The sources of Salmonella typhi infection and mode of transmission must be identified. [ABSTRACT FROM AUTHOR]

The unregulated use of antibiotics is linked with intensive poultry farming in developing economies. In low-and middle-income countries, the dissemination of antimicrobial resistance (AMR) has also been attributed to contamination, poor public health infrastructure and inadequate waste disposal practices. There are limited data on hygiene and waste disposal practices in small-scale commercial and household poultry farming and market sales in Bangladesh. Our objective was to explore human exposures, hygiene and waste disposal practices in poultry raising and processing to identify probable pathways for transmission of AMR bacteria. We employed mixed methods approaches of in-depth interviews and structured observations to assess exposures, hygiene behaviours and waste-disposal practices relating to poultry production in Bangladesh. Interviews (n = 18) were conducted with commercial poultry farmers, backyard poultry owners, and live poultry market workers. Structured observations were conducted for 6-h in five households, five commercial farms and five urban live bird markets to assess the frequency of transmission/exposure events in these settings. Interviews highlighted existing practices that can contribute to transmission of antimicrobial resistant bacteria from poultry to humans. In households and farms, untreated poultry waste and carcasses were disposed of on agricultural fields and in water bodies which may contaminate surface water and soil with poultry faeces. Biosecurity precautions were not used, and hands were rarely washed with soap after handling poultry. In urban markets, live poultry slaughter and processing was done on site with bare hands which were subsequently rinsed in water stored in containers without soap. Solid waste from poultry processing was disposed into municipal waste disposal stations and liquid waste was discarded into open drains. Structured observations revealed that workers in live poultry markets had the highest direct contact with poultry and poultry waste, almost tenfold higher than those working in poultry farms or with domestic poultry (59 vs 544 observed direct poultry exposure events) placing them at particularly high risk of exposure to faecal bacteria. Biosecurity measures were limited; in some cases, workers in commercial farms and urban markets had gloves and masks but often did not use them. In 88% (606/689) of exposure events no handwashing took place. Eating and drinking after handling poultry and without washing hands was observed in all three settings. These data suggest effective intervention strategies to reduce environmental contamination and to decrease risks of transmission should be prioritized. Data on prevalence of risk behaviours and AMR transmission to humans along environmental pathways can inform policy and intervention strategies. [ABSTRACT FROM AUTHOR]

Background: A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up.Methods: In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7-730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207.Findings: Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either vaccine or placebo, of whom 204 700 (102 552 vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0·09 (0·07 to 0·12) per 100 000 person-days versus 0·19 (0·15 to 0·23; adjusted protective efficacy 50%, 29 to 65). Vaccine protective efficacy was 52% (8 to 75) against all cholera episodes and 71% (27 to 88) against severe cholera episodes in participants aged 5 years to younger than 15 years. For participants aged 15 years or older, vaccine protective efficacy was 59% (42 to 71) against all cholera episodes and 59% (35 to 74) against severe cholera. The protection in the older age groups was sustained throughout the 2-year follow-up. In participants younger than 5 years, the vaccine did not show protection against either all cholera episodes (protective efficacy -13%, -68 to 25) or severe cholera episodes (-44%, -220 to 35).Interpretation: A single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group.Funding: Bill & Melinda Gates Foundation to the International Vaccine Institute. [ABSTRACT FROM AUTHOR]

Background Pregnant women are vulnerable to complications of cholera. Killed oral cholera vaccines (OCV) are not recommended for pregnant women though there is no evidence of harmful effects during pregnancy. We evaluated the effect of a killed OCV, Shanchol™, on pregnancy outcomes during an effectiveness trial of the vaccine in urban Bangladesh. Methodology Individuals ⩾1 year were invited to participate in the trial, conducted in 2011 in Dhaka, Bangladesh. Pregnancy by history was an exclusion criterion and all women of reproductive age (15–49 years) were verbally questioned about pregnancy at enrollment and prior to vaccination. Out of 48,414 women of reproductive age 286 women received the OCV unknowingly while pregnant. Out of these, we could recruit 69 women defined as exposed to OCV. Accordingly, we selected 69 pregnant women randomly from those who did not take the OCV (non-exposed to OCV). We evaluated adverse pregnancy outcome (spontaneous miscarriages, still births, or congenital malformations) between those who were exposed to OCV and those who were not exposed to OCV. Results About 16% of pregnant women exposed to OCV had pregnancy loss, as compared to 12% of unvaccinated pregnant women (P = 0.38). One congenital anomaly was observed and occurred in women non-exposed to OCV group. Models that adjusted for baseline characteristics that were unbalanced between the exposed and non-exposed groups, revealed a no elevation of risk of adverse pregnancy outcomes in vaccinees versus non-vaccinees (Adj. OR (95% CI): 0.45 (0.11–1.88). Conclusions No excess of adverse fetal outcomes associated with receipt of OCV was observed in this study. Trial registration: Clinical Trials.gov number NCT01339845 . [ABSTRACT FROM AUTHOR]

Key Clinical Message Atypical manifestation of Huntington's disease ( HD) could inform ongoing research into HD genetic modifiers not present in the primarily European populations studied to date. This work demonstrates that expanding HD genetic testing into under-resourced healthcare settings can benefit both local communities and ongoing research into HD etiology and new therapies. [ABSTRACT FROM AUTHOR]

Background: A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic.Methods: Nonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline.Results: A total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups.Conclusions: A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.). [ABSTRACT FROM AUTHOR]

Background: Cholera is endemic in Bangladesh, with outbreaks reported annually. Currently, the majority of epidemic cholera reported globally is El Tor biotype Vibrio cholerae isolates of the serogroup O1. However, in Bangladesh, outbreaks attributed to V. cholerae serogroup O139 isolates, which fall within the same phylogenetic lineage as the O1 serogroup isolates, were seen between 1992 and 1993 and in 2002 to 2005. Since then, V. cholerae serogroup O139 has only been sporadically isolated in Bangladesh and is now rarely isolated elsewhere. Methods: Here, we present case histories of four cholera patients infected with V. cholerae serogroup O139 in 2013 and 2014 in Bangladesh. We comprehensively typed these isolates using conventional approaches, as well as by whole genome sequencing. Phenotypic typing and PCR confirmed all four isolates belonging to the O139 serogroup. Findings: Whole genome sequencing revealed that three of the isolates were phylogenetically closely related to previously sequenced El Tor biotype, pandemic 7, toxigenic V. cholerae O139 isolates originating from Bangladesh and elsewhere. The fourth isolate was a non-toxigenic V. cholerae that, by conventional approaches, typed as O139 serogroup but was genetically divergent from previously sequenced pandemic 7 V. cholerae lineages belonging to the O139 or O1 serogroups. Conclusion: These results suggest that previously observed lineages of V. cholerae O139 persist in Bangladesh and can cause clinical disease and that a novel disease-causing non-toxigenic O139 isolate also occurs. [ABSTRACT FROM AUTHOR]

Background: Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting.Methods: We did this cluster-randomised open-label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845.Findings: Of 268,896 people present at baseline, we analysed 267,270: 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioural change, and 80,056 assigned to non-intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0·002) in the vaccination group and 45% (95% CI lower bound 24%; p=0·001) in the vaccination and behavioural change group. We recorded no vaccine-related serious adverse events.Interpretation: Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations.Funding: Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask. [ABSTRACT FROM AUTHOR]

Background: Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant. Methods: Cockroach extract (CE) was administered to mice intranasally (i.n.) daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR) was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate. Results: Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol. Conclusions: Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways. [ABSTRACT FROM AUTHOR]

Discusses the human antibody response to longus type IV pilus and the study of its prevalence among enterotoxigenic Escherichia coli (ETEC) in Bangladesh by using monoclonal antibodies. Reactivity and specificity of longus monoclonal antibodies; Prevalence of longus in ETEC isolates; Immune response to longus.