Correction: Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

[This corrects the article DOI: 10.1371/journal.ppat.1010952.].

Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

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.

Targeting SARS-CoV-2 non-structural protein 13 via helicase-inhibitor-repurposing and non-structural protein 16 through pharmacophore-based screening.

Novel drug compound hunting was carried out for SARS-CoV-2 proteins with low mutation susceptibility. The probability of escape mutation and drug resistance is lower if conserved microbial proteins are targeted by therapeutic drugs. Mutation rate of all SARS-CoV-2 proteins were analyzed via multiple sequence alignment Non-Structural Protein 13 and Non-Structural Protein 16 were selected for the current study due to low mutation rate among viral strains and significant functionality. Cross-species mutation rate analysis for NSP13 and NSP16 showed these are well-conserved proteins among four coronaviral species. Viral helicase inhibitors, identified using literature-mining, were docked against NSP13. Pharmacophore-based screening of 11,375 natural compounds was conducted for NSP16. Stabilities of top compounds inside human body were confirmed via molecular dynamic simulation. ADME properties and LD50 values of the helicase inhibitors and Ambinter natural compounds were analyzed. Compounds against NSP13 showed binding affinities between -10 and -5.9 kcal/mol whereby ivermectin and scutellarein showed highest binding energies of -10 and -9.9 kcal/mol. Docking of 18 hit compounds against NSP16 yielded binding affinities between -8.9 and -4.1 kcal/mol. Hamamelitannin and deacyltunicamycin were the top compounds with binding affinities of -8.9 kcal/mol and -8.4 kcal/mol. The top compounds showed stable ligand-protein interactions in molecular dynamics simulation. The analyses revealed two hit compounds against each targeted protein displaying stable behavior, high binding affinity and molecular interactions. Conversion of these compounds into drugs after in vitro experimentation can become better treatment options to elevate COVID management.

Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh.

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.).

Correction to: Tumour suppressor EP300, a modulator of paclitaxel resistance and stemness, is downregulated in metaplastic breast cancer.

In the original publication, Fig. 1 depicting the blot for EP300 in CAL51 cells (Fig. 1c) was unintentionally duplicated with that from MDA-MB-231 cells (Fig. 1d). The new figure given in this erratum depicts the correct EP300 blot in Fig. 1c.

Tumour suppressor EP300, a modulator of paclitaxel resistance and stemness, is downregulated in metaplastic breast cancer.

PURPOSE: We have previously described a novel pathway controlling drug resistance, epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer cells. Upstream in the pathway, three miRs (miR-106b, miR-93 and miR-25) target EP300, a transcriptional activator of E-cadherin. Upregulation of these miRs leads to the downregulation of EP300 and E-cadherin with initiation of an EMT. However, miRs regulate the expression of many genes, and the contribution to EMT by miR targets other than EP300 cannot be ruled out. METHODS: We used lentiviruses expressing EP300-targeting shRNA to downregulate its expression in MCF-7 cells as well as an EP300-knocked-out colon carcinoma cell line. An EP300-expression plasmid was used to upregulate its expression in basal-like CAL51 and MDA-MB-231 breast cancer cells. Drug resistance was determined by short-term proliferation and long-term colony formation assays. Stemness was determined by tumour sphere formation in both soft agar and liquid cultures as well as by the expression of CD44/CD24/ALDH markers. Gene expression microarray analysis was performed in MCF-7 cells lacking EP300. EP300 expression was analysed by immunohistochemistry in 17 samples of metaplastic breast cancer. RESULTS: Cells lacking EP300 became more resistant to paclitaxel whereas EP300 overexpression increased their sensitivity to the drug. Expression of cancer stem cell markers, as well as tumour sphere formation, was also increased in EP300-depleted cells, and was diminished in EP300-overexpressing cells. The EP300-regulated gene signature highlighted genes associated with adhesion (CEACAM5), cytoskeletal remodelling (CAPN9), stemness (ABCG2), apoptosis (BCL2) and metastasis (TGFB2). Some genes in this signature were also validated in a previously generated EP300-depleted model of breast cancer using minimally transformed mammary epithelial cells. Importantly, two key genes in apoptosis and stemness, BCL2 and ABCG2, were also upregulated in EP300-knockout colon carcinoma cells and their paclitaxel-resistant derivatives. Immunohistochemical analysis demonstrated that EP300 expression was low in metaplastic breast cancer, a rare, but aggressive form of the disease with poor prognosis that is characterized by morphological and physiological features of EMT. CONCLUSIONS: EP300 plays a major role in the reprogramming events, leading to a more malignant phenotype with the acquisition of drug resistance and cell plasticity, a characteristic of metaplastic breast cancer.

Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh: a cluster randomised open-label trial.

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.

District health information system (DHIS2) as integrated antimicrobial resistance surveillance platform: An exploratory qualitative investigation of the one health stakeholders' viewpoints in Ethiopia.

INTRODUCTION: There is an unmet need for One Health (OH) surveillance and reporting systems for antimicrobial resistance (AMR) in resource poor settings. District health information system, version 2 (DHIS2), is a globally recognized digital surveillance platform which has not been widely utilized for AMR data yet. Our study aimed to understand the local stakeholders' viewpoints on DHIS2 as OH-AMR surveillance platform in Jimma, Ethiopia which will aid its further context specific establishment. METHODS: We performed an exploratory qualitative study using semi-structured key informant interviews (KIIs) in Jimma Zone at Southwest Ethiopia. We interviewed 42 OH professionals between November 2020 and February 2021. Following verbatim transcription of the audio recordings of KIIs, we conducted thematic analysis. RESULTS: We identified five major themes which are important for understanding the trajectory of OH-AMR surveillance in DHIS2 platform. The themes were: (1) Stakeholders' current knowledge on digital surveillance platforms including DHIS2. (2) Stakeholders' perception on digital surveillance platform including DHIS2. (3) Features suggested by stakeholders to be included in the surveillance platform. (4) Comments from stakeholders on system implementation challenges. (5) Stakeholders' perceived role in the process of implementation. Despite several barriers and challenges, most of the participants perceived and suggested DHIS2 as a suitable OH-AMR surveillance platform and were willing to contribute at their current professional roles. CONCLUSIONS: Our study demonstrates the potential of the DHIS2 as a user friendly and acceptable interoperable platform for OH-AMR surveillance if the technology designers accommodate the stakeholders' concerns. Piloting at local level and using performance appraisal tool in all OH disciplines should be the next step before proceeding to workable format.

House dust mite interactions with airway epithelium: role in allergic airway inflammation.

House dust mite (HDM) allergens are the most prevalent allergens associated with asthma and rhinitis around the world. The mechanisms of allergic sensitization and allergic airway inflammation after exposure to HDM have been studied extensively, but many questions remain unanswered. Airway epithelial cells are the first line of defense against external antigens and are considered an important player in the development of allergic airway inflammation. Both genetic susceptibility to allergic sensitization and HDM composition play decisive roles in the outcome of HDM-epithelium interactions, especially regarding airway epithelial dysfunction and allergic inflammation. Interactions between HDM and the airway epithelium have consequences for both development of allergy and asthma and development of allergic airway inflammation. This review will describe in detail these interactions and will identify issues that require more study.

Preventive knowledge, attitude, and vaccination challenges for COVID-19 among Myanmar refugees and irregular migrants in Malaysia.

Access to vaccinations is crucial for everyone in the fight against the COVID-19 pandemic, regardless of migration or refugee status. This study explored COVID-19 prevention knowledge, attitudes, and vaccination challenges among refugees and irregular migrants from Myanmar in Malaysia. This study employed a descriptive mixed-method approach. Convenience sampling was used to conduct an online survey of 174 participants and two focus groups (N = 14). The majority (51.7 %) were refugees, and 48% were irregular migrant workers. In this study, 90.9% of the participants used social networks and social media chats to obtain information about COVID-19, 84.1% understood and found the vaccination campaign helpful, and 44.2% were aware of it. Although 70% of the participants considered vaccination crucial, 95% said that they would not take it because of fear of arrest and deportation, even though they considered vaccination necessary. Approximately 21.2% of the workers reported that their employers did not provide masks or hand sanitisers. Most of the participants (39.7 %) lived in dormitories provided by their employers. This puts them at a higher risk of infection because of the difficulty in practising social distancing. As part of COVID-19 prevention, the government should grant an amnesty period and work with migrant civil society organisations to administer vaccinations and effective measures for all immigrant populations in Malaysia.

Factors affecting access to healthcare for young people in the informal sector in developing countries: a systematic review.

Background: Young people are increasingly seeking employment in the informal sector due to increasing global unemployment. However, the precarious nature of work in the informal sectors, coupled with the high risk of occupational hazards, calls for a greater need for effective healthcare for informal sector workers, particularly young people. In addressing the health vulnerabilities of informal workers, systematic data on the determinants of health is a persistent challenge. Therefore, the objective of this systematic review was to identify and summarise the existing factors that affect access to healthcare among young people from the informal sector. Methods: We searched six data databases (PubMed, Web of Science, Scopus, ProQuest, Crossref, and Google Scholar), which was followed by hand searching. Then we screened the identified literature using review-specific inclusion/exclusion criteria, extracted data from the included studies and assessed study quality. Then we presented the results in narrative form, though meta-analysis was not possible due to heterogeneity in the study design. Results: After the screening, we retrieved 14 studies. The majority were cross-sectional surveys and were conducted in Asia (n = 9); four were conducted in Africa, and one in South America. Samples ranged in size from 120 to 2,726. The synthesised results demonstrate that problems of affordability, availability, accessibility, and acceptability of healthcare were barriers to young informal workers seeking healthcare. We found social networks and health insurance as facilitators of access for this group of people. Conclusion: To date, this is the most comprehensive review of the evidence on access to healthcare for young people in the informal sector. Our study finding highlights the key gaps in knowledge where future research could further illuminate the mechanisms through which social networks and the determinants of access to healthcare could influence the health and well-being of young people and thus inform policy development.

Use of antibiotics in poultry and poultry farmers- a cross-sectional survey in Pakistan.

Background: Antimicrobial resistance (AMR) which has been ascribed to be due to community carriage of antibiotic-resistant bacteria is highly prevalent in the WHO South-East Asia region. One of the major reasons for this is the misuse of antibiotics in animal farming practices and at the community level, which threatens both human and animal health. However, this problem of antibiotic misuse in poultry farms and in respective farmers is not well studied in countries like Pakistan. Methods: We conducted a cross-sectional study in rural Punjab to explore the current practices of antibiotic use in poultry and poultry farmers, associated factors, their healthcare-seeking behavior and biosecurity practices. Results: In the context of antibiotic use for poultry, 60% comprised of Colistin sulfate and Amoxicillin trihydrate whereas Colistin is considered as the last resort antibiotic. In addition, the significant consumption of antibiotics in poultry farms (60%) and poultry farmers (50%) was without prescription by either human health physicians or veterinarians. Most of the farms (85%) had no wastewater drainage system, which resulted in the direct shedding of poultry waste and antibiotic residue into the surrounding environment. The lack of farmers' education, professional farm training and farming experience were the most significant factors associated with antibiotic use and knowledge of AMR. Conclusion: Our study findings show that it is necessary for an integrated AMR policy with the inclusion of all poultry farmers to be educated, a mass awareness program to be undertaken and that strict antibiotic usage guidelines be available to them. Such initiatives are also important to ensure food safety and farm biosecurity practices.

The comparison of antioxidant properties and nutrigenomic redox-related activities of vitamin C, C-vitamers, and other common ascorbic acid derivatives.

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.

Users' perception of the OH-EpiCap evaluation tool based on its application to nine national antimicrobial resistance surveillance systems.

Introduction: Antimicrobial resistance (AMR) is a One Health (OH) challenge. To achieve or maintain an effective and efficient AMR surveillance system, it is crucial to evaluate its performance in meeting the proposed objectives, while complying with resource restrictions. The OH-EpiCap tool was created to evaluate the degree of compliance of hazard surveillance activities with essential OH concepts across the following dimensions: organization, operational activities, and impact of the surveillance system. We present feedback on the application of the OH-EpiCap tool from a user's perspective, based on the use of the tool to evaluate nine national AMR surveillance systems, each with different contexts and objectives. Methods: The OH-EpiCap was assessed using the updated CoEvalAMR methodology. This methodology allows the evaluation of the content themes and functional aspects of the tool and captures the user's subjective experiences via a strengths, weaknesses, opportunities, and threats (SWOT) approach. Results and Discussion: The results of the evaluation of the OH-EpiCap are presented and discussed. The OH-EpiCap is an easy-to-use tool, which can facilitate a fast macro-overview of the application of the OH concept to AMR surveillance. When used by specialists in the matter, an evaluation using OH-EpiCap can serve as a basis for the discussion of possible adaptations of AMR surveillance activities or targeting areas that may be further investigated using other evaluation tools.

'I Doubt Myself and Am Losing Everything I Have since COVID Came'-A Case Study of Mental Health and Coping Strategies among Undocumented Myanmar Migrant Workers in Thailand.

Migrant populations have always been vulnerable to a high burden of social exclusion, mental disorders, physical illnesses, and economic crises. The current COVID-19 pandemic has further created a frantic plight among them, particularly for undocumented migrant workers in the global south. We have conducted a mixed method study among the undocumented Myanmar migrant workers (UMMWs) in Thailand to explore how the COVID-19 disruption has impacted their mental health and what coping strategies they have adopted. Following the onset of COVID-19 and the recent coup d'état in Myanmar, our current study is the first attempt to understand the mental health status and predicament of this neglected migrant group. A total of 398 UMMWs were included in the online survey, of which 23 participated in qualitative interviews. The major mental health issues reported by the study participants were depression, generalized anxiety disorder, frustration, stress, and panic disorders, while loss of employment, worries about the pandemic, social stigma, lack of access to healthcare, lockdown, and fear of detention were the predominant contributing factors. In response, we identified two key coping mechanisms: coping at a personal level (listening to music, playing online game, praying, and self-motivation) and coping at a social level (chatting with family and friends and visiting religious institutions). These findings point to the importance of policy and intervention programs aimed at upholding mental health at such humanitarian conditions. Sustainable institutional mental health care support and social integration for the migrant workers, irrespective of their legal status, should be ensured.

Understanding transmission pathways and integrated digital surveillance potential of antimicrobial resistance in Ethiopia in a One Health approach: a mixed-method study protocol.

INTRODUCTION: Antimicrobial resistance (AMR) has a critical global impact, mostly affecting low- and middle-income countries. A major knowledge gap exists in understanding the transmission pathway of the gut colonisation with AMR bacteria between healthy humans and their animals in addition to the presence of those AMR bacteria in the surrounding environment. A One Health (OH) approach is necessary to address this multisectoral problem. METHODS AND ANALYSIS: This cross-sectional, mixed-method OH study design will use both quantitative and qualitative methods of data collection. Quantitative methods will be carried out to assess the prevalence and risk factors associated with multidrug resistant Gram-negative bacteria and vancomycin-resistant enterococci in humans, animals (cattle) and the environment. The focus will be on cattle rearing as an exposure risk for AMR among humans. The assessment of AMR in the population of Jimma, Ethiopia with or without exposure to cattle will reinforce the importance of OH research to identify the impending exchange of resistance profile between humans and animals as well as its ultimate dissemination in the surrounding environment.The targeted semistructured key stakeholder interviews will aid to strengthen the OH-AMR surveillance in Ethiopia by understanding the acceptability of an integrated AMR surveillance platform based on the District Health Information Software-2 and the feasibility of its context-specific establishment. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethics Committee, Norway, and the Institutional Review Board of Jimma University, Ethiopia. The study's data will be stored on a secure server known as Services for Sensitive Data hosted by the University of Oslo. In addition, the new European Union Global Data Protection Guidelines for data sharing, storage and protection will be followed. We will publish the results in peer-reviewed journals and present the findings at national and international conferences.

Evidence of Antimicrobial Resistance in Bats and Its Planetary Health Impact for Surveillance of Zoonotic Spillover Events: A Scoping Review.

As a result of the COVID-19 pandemic, as well as other outbreaks, such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread, and persistence of AMR at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wildlife has important implications for zoonotic pandemic surveillance, disease transmission, and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n = 38) that provided data on resistant bacteria in bats prior to 30 September 2022. There is substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types, and time. We found all major groups of Gram-positive and Gram-negative bacteria in bats, which are resistant to commonly used antibiotics. The most alarming issue is that recent studies have increasingly identified clinically significant multi-drug resistant bacteria such as Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing, and Colistin resistant Enterobacterales in samples from bats. This evidence of superbugs abundant in both humans and wild mammals, such as bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic preparedness as well as global AMR containment during pandemic events and beyond.

Planetary Health Education and Capacity Building for Healthcare Professionals in a Global Context: Current Opportunities, Gaps and Future Directions.

The emerging concept of planetary health needs to be discussed in a more organized and sustainable way within the global public health and healthcare disciplines. Therefore, planetary health should be considered a cardinal component of the global academic framework for healthcare professionals. The availability of related curricula and courses is crucial to equip health professionals in this relatively new discipline of planetary health. In this review article, we aimed to explore published articles and online databases of courses to summarize the available planetary health education opportunities and discussions for health professionals, to identify the gaps in resource allocation and to suggest future recommendations. We observed a visible resource inequity in the global south with the lack of a universal planetary health module for healthcare professionals. Additionally, there is minimal inclusion of allied health disciplines in this learning process. We therefore recommend a dedicated network of motivated healthcare professionals and regional hubs with an agenda to ensure a comprehensive, uniform, and inclusive planetary health education curriculum and practice.

Iron Overload and Breast Cancer: Iron Chelation as a Potential Therapeutic Approach.

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.

Prevalence, etiology and antibiotic resistance patterns of community-acquired urinary tract infections in Dhaka, Bangladesh.

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.