FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.

MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression. It remains unclear how the efficiency of RNA silencing could be influenced by RNA-binding proteins associated with the microRNA-induced silencing complex (miRISC). Here we report that fused in sarcoma (FUS), an RNA-binding protein linked to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), interacts with the core miRISC component AGO2 and is required for optimal microRNA-mediated gene silencing. FUS promotes gene silencing by binding to microRNA and mRNA targets, as illustrated by its action on miR-200c and its target ZEB1. A truncated mutant form of FUS that leads its carriers to an aggressive form of ALS, R495X, impairs microRNA-mediated gene silencing. The C. elegans homolog fust-1 also shares a conserved role in regulating the microRNA pathway. Collectively, our results suggest a role for FUS in regulating the activity of microRNA-mediated silencing.

Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency.

A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

Polymorphisms in Innate and Adaptive Immune Genes in Subjects with Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

Innate and adaptive immunity play a crucial role in allergic bronchopulmonary aspergillosis (ABPA) pathogenesis. We performed next-generation sequencing using the Illumina TruSight One panel (4,811 human disease-associated genes, at least 20 × coverage) and selected 22 known immune genes (toll-like receptors (TLRs), C-type lectin, interleukin-4 receptor, and others). We included ABPA (n = 18), asthma without ABPA (n = 12), and healthy controls (n = 8). We analyzed 3011 SNPs from 22 genes and identified 145 SNPs (13 genes) that were present only in the disease groups and absent in controls. The SNP frequency overall was significantly higher in ABPA than in asthmatics (89/145 [61.4%] vs. 56/145 [38.6%], p = 0.0001). The SNP frequency in the TLR10 gene was also significantly higher in ABPA than in asthma (p = 0.017). Association analysis further revealed three genes having significant associations. Of these, NOS3 and HLA-DQB1 are associated with antimicrobial activity and adaptive immunity. More extensive studies are required to confirm our findings.

Including older people in health and social care research: best practice recommendations based on the INCLUDE framework.

BACKGROUND: Older people are often explicitly or implicitly excluded from research, in particular clinical trials. This means that study findings may not be applicable to them, or that older people may not be offered treatments due to an absence of evidence. AIMS: The aim of this work was to develop recommendations to guide all research relevant to older people. METHODS: A diverse stakeholder group identified barriers and solutions to including older people in research. In parallel, a rapid literature review of published papers was undertaken to identify existing papers on the inclusion of older people in research. The findings were synthesised and mapped onto a socio-ecological model. From the synthesis we identified themes that were developed into initial recommendations that were iteratively refined with the stakeholder group. RESULTS: A range of individual, interpersonal, organisational, community and policy factors impact on the inclusion of older people in research. A total of 14 recommendations were developed such as removing upper age limits and comorbidity exclusions, involving older people, advocates and health and social care professionals with expertise in ageing in designing the research, and considering flexible or alternative approaches to data collection to maximise opportunities for participation. We also developed four questions that may guide those developing, reviewing and funding research that is inclusive of older people. CONCLUSION: Our recommendations provide up to date, practical advice on ways to improve the inclusion of older people in health and care research.

Interventions to improve the nutritional status of children under 5 years in Ethiopia: a systematic review.

OBJECTIVE: To conduct a systematic review of experimental or quasi-experimental studies that aimed to improve the nutritional status of children under 5 years of age in Ethiopia. DESIGN: Embase, MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsychINFO, and Academic Search Database were used to locate peer-reviewed studies, and Google Scholar and Open Dissertation were used to locate grey literatures. All searches were conducted between 2000 and November 2022. SETTING: Ethiopia. PARTICIPANTS: Pregnant women and mothers with children aged 0-59 months. RESULTS: Ten cluster randomised controlled trials (RCT), six quasi-experimental studies and two individual RCT were included. Out of the identified eighteen studies, three studies targeted pregnant mothers. Our findings showed that almost two-thirds of published interventions had no impact on childhood stunting and wasting, and more than half had no impact on underweight. Some behaviour change communication (BCC) interventions, food vouchers, micronutrient supplementation and quality protein maize improved stunting. Similarly, BCC and fish oil supplementation showed promise in reducing wasting, while BCC and the provision of quality protein maize reduced underweight. Additionally, water, sanitation and hygiene (WaSH) interventions provided to pregnant mothers and children under 2 years of age were shown to significantly reduce childhood stunting. CONCLUSION: Future childhood nutritional interventions in Ethiopia should consider adopting an integrated approach that combines the positive effects of interdependent systems such as BCC, food supplemental programmes (e.g. boosting protein and micronutrients), health interventions (e.g. strengthening maternal and childcare), WaSH and financial initiatives (e.g. monetary support and income schemes).

The gene expression and proteomic profiling of Acanthamoeba isolates.

INTRODUCTION: The free-living protozoan Acanthamoeba can cause severe keratitis known as Acanthamoeba Keratitis (AK) and granulomatous amoebic encephalitis (GAE). The pathogenesis of Acanthamoeba includes intricate interactions between the organism and the host's immune system. The downstream analysis of a well-annotated genome assembly along with proteomic analysis can unravel several biological processes and aid in the identification of potential genes involved in pathogenicity. METHODS: Based on the next-generation sequencing data analysis, genes including lysophospholipase, phospholipase, S8/S53 peptidase, carboxylesterase, and mannose-binding protein were selected as probable pathogenic targets that were validated by conventional PCR in a total of 30 Acanthamoeba isolates. This was followed by real-time PCR for the evaluation of relative gene expression in the keratitis and amoebic encephalitis animal model induced using keratitis (CHA5), encephalitis (CHA24) and non-pathogenic environmental isolate (CHA36). In addition, liquid chromatography-mass spectrometry (LC-MS/MS) was performed for keratitis, encephalitis, and non-pathogenic environmental isolate before and after treatment with polyhexamethylene biguanide (PHMB). RESULTS: The conventional PCR demonstrated the successful amplification of lysophospholipase, phospholipase, S8/S53 peptidase, carboxylesterase, and mannose-binding protein genes in clinical and environmental isolates. The expression analysis revealed phospholipase, lysophospholipase, and mannose-binding genes to be significantly upregulated in the keratitis isolate (CHA 5) during AK in the animal model. In the case of the amoebic encephalitis model, phospholipase, lysophospholipase, S8/S53 peptidase, and carboxylesterase were significantly upregulated in the encephalitis isolate compared to the keratitis isolate. The proteomic data revealed differential protein expression in pathogenic versus non-pathogenic isolates in the pre and post-treatment with PHMB. CONCLUSION: The gene expression data suggests that lysophospholipase, phospholipase, S8/S53 peptidase, carboxylesterase, and mannose-binding protein (MBP) could play a role in the contact-dependent and independent mechanisms of Acanthamoeba pathogenesis. In addition, the proteomic profiling of the 3 isolates revealed differential protein expression crucial for parasite growth, survival, and virulence. Our results provide baseline data for selecting possible pathogenic targets that could be utilized for designing knockout experiments in the future.

Socioeconomic disparities in Rwanda's under-5 population's growth tracking and nutrition promotion: findings from the 2019-2020 demographic and health survey.

BACKGROUND: Regular growth monitoring can be used to evaluate young children's nutritional and physical health. While adequate evaluation of the scope and quality of nutrition interventions is necessary to increase their effectiveness, there is little research on growth monitoring coverage measurement. The purpose of this study was to investigate socioeconomic disparities in under-5 Rwandan children who participate in growth monitoring and nutrition promotion. METHODS: We used data from the 2019-2020 Rwanda Demographic and Health Survey (RDHS), which included 8092under-5 children. Percentage was employed in univariate analysis. To examine the socioeconomic inequalities, concentration indices and Lorenz curves were used in growth monitoring and nutrition promotion among under-5 children. RESULTS: A weighted prevalence of 33.0% (95%CI: 30.6-35.6%) under-5 children growth monitoring and nutrition promotion was estimated. Growth monitoring and nutrition promotion among under-5 children had higher uptake in the most disadvantaged cohort, as the line of equality sags below the diagonal line in Lorenz curve. Overall, there was pro-poor growth monitoring and nutrition promotion among under-5 in Rwanda (Conc. Index = 0.0994; SE = 0.0111). Across the levels of child and mother's characteristics, the results show higher coverage of under-5 growth monitoring and nutrition promotion in the most socioeconomic disadvantaged cohort. CONCLUSION: The study found a pro-poor disparity in growth monitoring and nutrition promotion among under-5 children in Rwanda. By implication, the most disadvantaged children had a higher uptake of growth monitoring and nutrition promotion. The Rwanda government should develop policies and programmes to achieve the universal health coverage for the well-off and underserved population.

Test of a Homeopathic Algorithm for COVID-19: the Importance of a Broad Perspective.

BACKGROUND: Most of the symptoms of coronavirus disease 2019 (COVID-19) are covered by large repertory rubrics and hence many remedies have been proposed as "genus epidemicus". The aim of this study was to combine the information from various data collections to prepare a COVID-19 Bayesian mini-repertory/an algorithm-based application (app) and test it. METHODS: In July 2021, 1,161 COVID-19 cases from 100 practitioners globally were combined. These data were used to calculate "condition-confined" likelihood ratios (LRs) for 59 symptoms of COVID-19. Out of these, 35 symptoms of the 11 medicines that had at least 20 cases each were considered. The information was entered in a spreadsheet (algorithm) to calculate combined LRs of specific combinations of symptoms. The algorithm contained the medicines Arsenicum album, Belladonna, Bryonia alba, Camphora, Gelsemium sempervirens, Hepar sulphuris, Mercurius solubilis, Nux vomica, Phosphorus, Pulsatilla and Rhus toxicodendron. To test concordance, the doctors were then invited to re-enter the symptoms of their cases into this algorithm. RESULTS: The algorithm was re-tested on 358 cases, and concordance was seen in 288 cases. On analysis of the data, bias was noticed in the Merc group, which was therefore excluded from the algorithm. The remaining 10 medicines, representing 81.8% of all cases, were included in the preparation of the next version of the homeopathic mini-repertory and app. CONCLUSION: The Bayesian mini-repertory and app is based on qualitative clinical experiences of various doctors in COVID-19 and gives indications for specific medicines for common COVID-19 symptoms. It is freely available [English: https://hpra.co.uk/; Spanish: https://hpra.co.uk/es ] for further testing and utilization by the profession.

Homeopathic Medicines in Second Wave of COVID-19: Prognostic Factor Research.

BACKGROUND: The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave. METHODS: This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS: Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album, Pulsatilla nigricans, Belladonna, Gelsemium sempervirens, Hepar sulphuris, Phosphorus, Rhus toxicodendron and Mercurius solubilis. By calculating LR, the prescribing indications of these nine medicines were ascertained. CONCLUSION: Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines.

Effectiveness of sensory adaptive dental environments to reduce psychophysiology responses of dental anxiety and support positive behaviours in children and young adults with intellectual and developmental disabilities: a systematic review and meta-analyses.

BACKGROUND: People with Intellectual and developmental disabilities (IDDs) experience oral health inequality due to myriad of risk factors and complex needs. Sensory processing difficulties, maladaptive behaviours and dental anxiety contribute to difficulties in receiving preventive and routine dental treatments. This study aimed to systematically review the evidence on the effectiveness of sensory adaptive dental environments (SADE) for children and young adults (up to the ages 24 years) with IDD to address cooperation and dental anxiety. METHODS: This review was reported according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE (Ovid), The Cochrane Library, Embase, Google Scholar, Web of Science and OT Seeker were searched using appropriate terms to identify Randomised Control Trails (RCTs) that matched inclusion criteria. Screening was conducted by two reviewers after de-duplication based on titles and abstracts followed by full text retrieval. Quality of the included studies was assessed using Cochrane Risk of Bias (ROB)-2 for crossover trials and data extracted by two reviewers. The details of the interventions and effectiveness were compared and discussed narratively, and comparable outcomes were included to meta-analyses using R software. RESULTS: A total of 622 articles were identified and five articles met eligibility for inclusion. Three studies used multi-sensory adaptations and one used single sensory adaptation of music. Narrative synthesis showed some evidence of SADE reducing magnitude and duration, although, questionable for reducing the number of maladaptive behaviours. Two studies demonstrated conflicting evidence of the effect of SADE on cooperation. Three studies demonstrated significant positive impact of SADE on psychophysiological outcomes. Despite an overall tendency to favour SADE, no statistically significant difference of maladaptive behaviours was found between SADE and regular dental environment (RDE) (Standardised mean change (SMC) = 0.51; 95% Confidence Interval (CI) -0.20 to 1.22; p = 0.161). SADE was superior to RDE (SMC -0.66; 95% CI -1.01 to -0.30; p = < 0.001) in reducing psychophysiological responses of dental anxiety. CONCLUSION: Current evidence suggests that adapting visual, tactile, and auditory aspects of the dental environment in a single or multi-sensory approach demonstrates small positive effects on psychophysiological responses and maladaptive behaviours of dental anxiety for people with IDD. TRIAL REGISTRATION: The title of this review was registered with PROSPERO (CRD42022322083).

Functional Proteins from Biovalorization of Peanut Meal: Advances in Process Technology and Applications.

Environmental costs associated with meat production have necessitated researchers and food manufacturers to explore alternative sources of high-quality protein, especially from plant origin. Proteins from peanuts and peanut-by products are high-quality, matching industrial standards and nutritional requirements. This review contributes to recent developments in the production of proteins from peanut and peanut meal. Conventional processing techniques such as hot-pressing kernels, use of solvents in oil removal, and employing harsh acids and alkalis denature the protein and damage its functional properties, limiting its use in food formulations. Controlled hydrolysis (degree of hydrolysis between 1 and 10%) using neutral and alkaline proteases can extract proteins and improve peanut proteins' functional properties, including solubility, emulsification, and foaming activity. Peanut proteins can potentially be incorporated into meat analogues, bread, soups, confectionery, frozen desserts, and cakes. Recently, pretreatment techniques (microwave, ultrasound, high pressure, and atmospheric cold plasma) have been explored to enhance protein extraction and improve protein functionalities. However, most of the literature on physicochemical pretreatment techniques has been limited to the lab scale and has not been analysed at the pilot scale. Peanut-derived peptides also exhibit antioxidant, anti-hypertensive, and anti-thrombotic properties. There exists a potential to incorporate these peptides into high-fat foods to retard oxidation. These peptides can also be consumed as dietary supplements for regulating blood pressure. Further research is required to analyse the sensory attributes and shelf lives of these novel products. In addition, animal models or clinical trials need to be conducted to validate these results on a larger scale.

The thermal resistance and targeting release of zein-sodium alginate binary complexes as a vehicle for the oral delivery of riboflavin.

Riboflavin (RF) is one kind of vitamin B, which has low bioavailability due to the low water solubility and the high photosensitivity during food processing and storage. The anti-solvent precipitation method was applied to fabricate a zein-sodium alginate (SA) binary complexes delivery system with the loading of RF, which was aimed to enhance the delivery efficiency, stability, and controlled release of RF in the gastrointestinal (GI) tract. The formation mechanism, physicochemical properties as well as the digestion behaviors were investigated. The incorporation of SA significantly increased the diameter and decreased the surface positive charge of the nanoparticles. The surface morphology of the nanoparticles was characterized using the scanning electron microscope. The FTIR analysis revealed that the electrostatic attraction was the dominant binding force in the formation of the zein-SA binary complexes nanoparticles. In addition, the study on the in vitro release process showed that the zein-SA nanoparticles could delay the release of the RF under the simulated GI tract conditions, which improved their oral bioavailability. In summary, the zein-SA nanoparticle is an effective vehicle for the oral delivery of RF as well as other vitamins and bioactives in the applications of food and nutrition.

Health-related quality of life outcomes after neoadjuvant chemoradiotherapy for rectal cancer in NRG Oncology/NSABP R-04.

BACKGROUND: There has been limited evaluation of health-related quality of life (HRQOL) in rectal cancer patients receiving neoadjuvant chemoradiotherapy. HRQOL outcomes in the National Surgical Adjuvant Breast and Bowel Project R-04 trial are examined in this article. METHODS: Between 2004 and 2010, R-04 patients were invited to enroll in the HRQOL substudy, with questionnaires administered before randomization, after completion of chemoradiotherapy, and 1-year after surgery. HRQOL measures included: Functional Assessment of Cancer Therapy for colorectal cancer (FACT-C); Short Form-36v.2 Vitality scale; a treatment-specific symptom scale; and the FACT neurotoxicity scale. A 5-year postsurgery assessment was added to the protocol in 2012. Mixed-effects models examined neoadjuvant therapy treatment effects in the 1-year sample and models that explored associations of host factors and treatment impact on 5-year HRQOL. RESULTS: A total of 1373 patients completed baseline HRQOL and at least one additional assessment. The average age was 58 years (range, 23-85 years), male (68%), and 59% Stage II. There were no statistically significant differences in HRQOL outcomes by treatment arm, but HRQOL worsened from baseline to postneoadjuvant chemoradiotherapy, with statistically significant effect sizes changes ranging from 0.6 (Vitality) to 0.9 (FACT-C Trial Outcome Index). Neurotoxicity was greater in the oxaliplatin-treated groups. Obese/overweight patients had statistically significantly worse FACT-C Trial Outcome Index scores than did underweight/normal weight groups. At 5 years, younger patients and those with normal baseline weight had statistically significantly better physical function scores and older patients had better mental health outcomes. CONCLUSIONS: HRQOL did not differ across the four R-04 treatment arms; however, host factors explained significant variation in posttreatment HRQOL. CLINICALTRIALS: gov: NCT00058474 (https://ClinicalTrials.gov/ct2/show/NCT00058474). LAY SUMMARY: This article reports on the health-related quality of life (HRQOL) outcomes of patients treated with four different chemotherapy regimens combined with radiation in rectal cancer patients before definitive surgical treatment. There were no significant differences in HRQOL by treatment regimen, but all patients experienced decreased vitality (energy) and physical functioning. By 1 year after treatment, most patients had returned to pretreatment vitality and physical functioning, with the exception of increased neurotoxicity. In a subsample of patients assessed at 5 years after surgery, physical function was better in those who at pretreatment were younger, normal weight, and had better performance status. Mental function was better in those who at pretreatment were older and had better performance status.

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

BACKGROUND: Inflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling. METHODS: We conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg-1) over 6 months in patients with group 1 PAH. Co-primary end-points were safety, defined by incidence and severity of adverse events, and change in pulmonary vascular resistance. Separately, a mendelian randomisation study was undertaken on 11 744 individuals with European ancestry including 2085 patients with idiopathic/heritable disease for the IL-6 receptor (IL6R) variant (rs7529229), known to associate with circulating IL-6R levels. RESULTS: We recruited 29 patients (male/female 10/19; mean±sd age 54.9±11.4 years). Of these, 19 had heritable/idiopathic PAH and 10 had connective tissue disease-associated PAH. Six were withdrawn prior to drug administration; 23 patients received at least one dose of tocilizumab. Tocilizumab was discontinued in four patients owing to serious adverse events. There were no deaths. Despite evidence of target engagement in plasma IL-6 and C-reactive protein levels, both intention-to-treat and modified intention-to-treat analyses demonstrated no change in pulmonary vascular resistance. Inflammatory markers did not predict treatment response. Mendelian randomisation did not support an effect of the lead IL6R variant on risk of PAH (OR 0.99, p=0.88). CONCLUSION: Adverse events were consistent with the known safety profile of tocilizumab. Tocilizumab did not show any consistent treatment effect.

Identification of genetic loci simultaneously associated with multiple cardiometabolic traits.

BACKGROUND AND AIMS: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits. METHODS AND RESULTS: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple loci reached genome-wide levels of significance (N = 145-333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10-8). We sought replication of these four loci in an independent set of seven trait-specific GWAS meta-analyses. GRB14-COBLL1 showed the most consistent replication, revealing nominally significant associations (P < 0.05) with all traits except DBP. CONCLUSIONS: Our analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.

Experiences of young Australian mothers with infant feeding.

BACKGROUND: Despite the overwhelming evidence of health and other benefits of breastfeeding and recommendations to breastfeed by peak health bodies, breastfeeding rates are significantly lower than recommended in Australia and globally. Young mothers are identified as being at high risk of not breastfeeding their infants according to infant feeding recommendations. This study aimed to gain an in-depth understanding of young Australian mothers' experiences of infant feeding, and to explore the factors which facilitated or hindered adherence to recommended breastfeeding practices. METHODS: Purposive and snowball sampling were used to recruit young mothers in Australia (n = 17) aged 18-25 years who had given birth to their first child within the last two years. Data were collected through semi-structured interviews via online videoconferencing. Interviews were audio-recorded, transcribed verbatim, coded, and subsequently analysed. Thematic analysis was conducted using Quirkos, a qualitative data management and analysis software. RESULTS: Four major themes were identified: Breastfeeding is challenging; Feeling judged about infant feeding choices; Experiences with breastfeeding support; and Experiences and views on breastfeeding education. Most mothers reported experiencing breastfeeding challenges, particularly those arising from lactation difficulties, yet many were able to overcome these challenges through their determination to breastfeed. Many mothers expressed perceiving judgement from others for breastfeeding in public. Some mothers who were bottle feeding their infants, whether with expressed breast milk or infant formula, felt that they were being judged for using a bottle. Many mothers reported professional, partner, family, and peer support as critical facilitators to the continuation of breastfeeding. Most mothers shared positive experiences of attending breastfeeding education sessions, but indicated the need for community education to reduce judgement toward mothers' infant feeding decisions. CONCLUSIONS: The barriers and enablers to infant feeding experienced by young mothers are similar to those experienced by mothers of all ages. Young mothers experience significant breastfeeding challenges and need support from partner, family, peers, and professionals to continue breastfeeding in line with recommendations. Breastfeeding campaigns to support young mothers should be aimed at the wider community to increase awareness of breastfeeding challenges, reduce stigma associated with breastfeeding in public, and to support mothers in their infant feeding decisions.

Prevalence and determinants of hypertension among urban slum dwellers in Bangladesh.

BACKGROUND: In low- and middle- income countries such as Bangladesh, urban slum dwellers are particualry vulnerable to hypertension due to inadequate facilities for screening and management, as well as inadequate health literacy among them. However, there is scarcity of evidence on hypertension among the urban slum dwellers in Bangladesh. The present study aimed to determine the prevalence and factors associated with hypertension among urban slum dwellers in Bangladesh. METHODS: Data were collected as part of a large-scale cross-sectional survey conducted by Building Resources Across Communities (BRAC) between October 2015 and January 2016. The present analysis was performed among 1155 urban slum dwellers aged 35 years or above. A structured questionnaire was adminstered to collect data electronically and blood pressure measurements were taken using standardised procedures. Binary logistic regression with generalized estimating equation modelling was performed to estimate the factors associated with hypertension. RESULTS: The prevalence of hypertension was 28.3% among urban slum dwellers aged 35 years and above. In adjusted analysis, urban slum dwellers aged 45-54 years (AOR: 1.64, 95% CI: 1.17-2.28), 55-64 years (AOR: 2.47, 95% CI: 1.73-3.53) and ≥ 65 years (AOR: 2.34, 95% CI: 1.47-3.72), from wealthier households (AOR: 1.94, 95% CI: 1.18-3.20), sleeping < 7 h per day (AOR: 1.87, 95% CI: 1.39-2.51), who were overweight (AOR: 1.53, 95% CI: 1.09-2.14) or obese (AOR: 2.34, 95% CI: 1.71-3.20), and having self-reported diabetes (AOR: 3.08, 95% CI: 1.88-5.04) had an increased risk of hypertension. Moreover, 51.0% of the participants were taking anti-hypertensive medications and 26.4% of them had their hypertension in control. CONCLUSIONS: The findings highlight a high burden of hypertension and poor management of it among the slum dwellers in Bangladesh requiring a novel approach to improve care. It is integral to effectively implement the available national non-communicable disease (NCD) control guidelines and redesign the current urban primary health care system to have better coordination.

Occurrence of Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Patients with Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

BACKGROUND: Whether cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations contribute to the high prevalence of allergic bronchopulmonary aspergillosis (ABPA) in India remains unknown. We aimed to evaluate the occurrence of CFTR mutations in subjects with ABPA complicating asthma. METHODS: We sequenced the CFTR gene using genomic DNA from blood on the Illumina NextSeq500 platform. Before undertaking zygosity analysis by genome analysis toolkit, the known or novel single nucleotide polymorphisms (SNPs) and indels were called. For rigorous analysis, we included only high-quality SNPs (scores > 500) and coverage ranging from 30 × 150x. RESULTS: We included 18, 12, and eight adult participants of ABPA, asthma, and healthy controls, respectively. The frequency of SNPs was higher in asthmatic subjects than ABPA or healthy controls, albeit not statistically significant (9/12 [75%] vs. 11/18 [61.1%] vs. 3/8 [37.5%], p = 0.24). Of the 38 subjects, 23 yielded 50 variants (healthy controls [n = 5], ABPA [n = 22], asthma [n = 23]) corresponding to six SNPs not previously linked with ABPA. Of these, four SNPs (rs213950, rs200735475, rs1800113, and rs1800136) were catalogued in the NCBI database. We identified two novel SNPs (chr7:117250703, chr7:117282655) in four (ABPA [n = 1], asthma [n = 3]) subjects without corresponding reference SNP. Most SNPs (85.5%) were heterozygous. The frequency of SNPs was higher in ABPA subjects with high-attenuation mucus (52.2%) and bronchiectasis (39.1%) than serological ABPA (8.7%). CONCLUSIONS: Our study suggests the role of CFTR mutations in the pathogenesis of ABPA. The SNPs in the CFTR gene may contribute to disease severity in ABPA. Larger studies are required to confirm our findings.

Rainwater harvesting and water balance simulation-optimization scheme to plan sustainable second crop in small rain-fed systems.

Environmental degradation in the form of water shortage and uncertainty has severely affected the food systems across the globe. Especially in India, which is dominated by rain-fed farmers, the need for sustainable water resource and its management at farm level is imperative for farming livelihoods and food security of the country. Rainwater harvesting in on-farm reservoirs (OFR) can enable crop diversification, year round cropping and seasonal vegetable cultivation in rain-fed farming systems in India. However appropriate sizing of OFR remains a serious concern especially for small and marginal farmers with limited land holdings. In this study, a novel and comprehensive simulation-optimization model was developed to determine the optimal size and utilization of OFR. The simulation consisted of water balance of soil and OFR using hydrological analysis for last 28 years, through which supplement irrigation needs and, rainwater harvesting potential was estimated. Optimal use of available water in OFR was designed using a multi-stage process wherein the model generated, compared and screened appropriate vegetable plans for Rabi cultivation. The model was simulated for different OFR sizes and the optimal size was chosen based on its economic feasibility. To demonstrate the model, a case study was simulated wherein high supplement irrigation was estimated, indicating a severe limitation in rain-fed farming. A minimum OFR size of 9.9% of the total land was required. With an increase in OFR sizes, the profits increased however, the growth rate declined as the cropping area was reduced. An OFR size of 15.5% of total land was found to be optimal which gave benefit-cost ratio and payback period of 2.4 and 6.8 years respectively. Trends in cultivation plans for different sizes of OFR was observed wherein for small OFR sizes, the model generated fewer options of cultivation plans and preferred crops with high water productivity over crops with high profitability. The proposed model is generic and applicable at multiple scales and scenarios. The model could be used by environmental decision makers, farm managers, policy makers and researchers to determine the feasibility of any water resource intervention using an ecosystem centric approach when multiple scenarios of cultivation are possible.

Barriers and enablers in the implementation and sustainability of toothbrushing programs in early childhood settings and primary schools: a systematic review.

BACKGROUND: Untreated dental caries negatively impacts a child's quality of life including overall health and wellbeing, growth and development, social interaction ability, and school attendance. School-based toothbrushing programs have been recognised as an effective intervention to reduce the burden of dental caries. However, limited information is available to understand the real-world enablers and challenges in the implementation and sustainability of toothbrushing programs. This review aims to understand the barriers and enablers in the implementation and sustainability of toothbrushing programs in early childhood settings and primary schools. METHODS: Five electronic databases [i.e., CINAHL (EBSCO), Medline (EBSCO), EMBASE (Ovid), Web of Science, and PsycINFO] and backward citation chasing were performed. The last updated databases searches were conducted in May 2022. Studies reporting on barriers and enablers in the implementation and sustainability of toothbrushing programs in early childhood settings or primary schools were included in the review. The methodological quality of included studies was assessed by using Joanna Briggs Institute [JBI] and mixed methods appraisal tool [MMAT] critical appraisal tools and results were reported in accordance with PRISMA guidelines. RESULTS: A total of six studies met the eligibility criteria and were included in the review. Toothbrushing programs in early childhood settings and primary schools were mostly implemented under the supervision of staff and teachers. A positive attitude of the staff, the flexibility of toothbrushing sessions, involvement of community volunteers and parents were a few of the identified enablers. However, the timing of the communication of the program, inadequate transfer of information among staff, frequent staffing turnover, lack of parental support, and staff feeling overburdened while acting as pseudo parents were frequently reported as barriers. CONCLUSION: The results of this systematic review identify key enablers and barriers for toothbrushing programs in early childhood settings and primary schools which need to be considered for developing oral health promotion initiatives.