Search

Background: Lead, a potent neurotoxin, causes irreversible damage to the nervous system, and low- and middle-income countries face huge health and economic productivity losses due to childhood lead exposure. In Bangladesh, informal Used Lead Acid Battery (ULAB) recycling sites are an important source of lead pollution. Little is known about lead awareness among communities exposed to ULAB recycling. Therefore, this study aims to assess knowledge, attitudes, and practices related to lead pollution among caregivers of young children and adolescents living adjacent to informal ULAB sites., Methods: A cross-sectional study was conducted among 732 mothers of young children and adolescents in 4 districts of Bangladesh (survey and observation). Simple and multiple linear regression was conducted to describe patterns and predictors of lead-related knowledge and practices., Results: 60% of respondents had heard the name 'lead' ("shisha"). The mean knowledge score was low (19 out of 44). Residents of high-risk districts, male respondents, and those with more than 5 years of schooling were significantly more likely to have higher knowledge scores than others. In terms of attitude, 52% of respondents perceived lead to be risky for human health but 43% thought lead pollution was controllable. Observation of households for lead exposure revealed that 63% of children and adolescents play or pass by ULAB sites, 29% ate non-food items, 41% of households had visible paint chips on the walls, 59% households used polished turmeric and 15% used lead-soldered cans to store foods. Among protective practices, 70% reported cleaning floors, 84% consumed iron-rich foods, and 48% consumed calcium-rich foods., Conclusions: The population had a high potential for lead exposure. Their knowledge about lead was limited, and risk perception was moderate. To reduce lead exposure and increase knowledge and awareness among the at-risk population, it is crucial to take measures such as mass awareness campaigns through media and schools. It is important to strengthen the implementation of existing policies, such as policies on leaded gasoline, paints, and lead-acid batteries, that can address the sources of lead exposure for the community., (© 2024. The Author(s).)

Targeting exhausted CD8+ T-cell (TEX)-induced aggravated cancer stem cells (CSC) holds immense therapeutic potential. In this regard, immunomodulation via Neem Leaf Glycoprotein (NLGP), a plant-derived glycoprotein immunomodulator is explored. Since former reports have proven immune dependent-tumor restriction of NLGP across multiple tumor models, we hypothesized that NLGP might reprogram and rectify TEX to target CSCs successfully. In this study, we report that NLGP's therapeutic administration significantly reduced TEX-associated CSC virulence in in vivo B16-F10 melanoma tumor model. A similar trend was observed in in vitro generated TEX and B16-F10/MCF7 coculture setups. NLGP rewired CSCs by downregulating clonogenicity, multidrug resistance phenotypes and PDL1, OCT4, and SOX2 expression. Cell cycle analysis revealed that NLGP educated-TEX efficiently pushed CSCs out of quiescent phase (G0G1) into synthesis phase (S), supported by hyper-phosphorylation of G0G1-S transitory cyclins and Rb proteins. This rendered quiescent CSCs susceptible to S-phase-targeting chemotherapeutic drugs like 5-fluorouracil (5FU). Consequently, combinatorial treatment of NLGP and 5FU brought optimal CSC-targeting efficiency with an increase in apoptotic bodies and proapoptotic BID expression. Notably a strong nephron-protective effect of NLGP was also observed, which prevented 5FU-associated toxicity. Furthermore, Dectin-1-mediated NLGP uptake and subsequent alteration of Notch1 and mTOR axis were deciphered as the involved signaling network. This observation unveiled Dectin-1 as a potent immunotherapeutic drug target to counter T-cell exhaustion. Cumulatively, NLGP immunotherapy alleviated exhausted CD8+ T-cell-induced CSC aggravation. Implications: Our study recommends that NLGP immunotherapy can be utilized to counter ramifications of T-cell exhaustion and to target therapy elusive aggressive CSCs without evoking toxicity., (©2024 American Association for Cancer Research.)

A worrying new outbreak of Monkeypox (Mpox) in humans is caused by the Mpox virus (MpoxV). The pathogen has roughly 28 hypothetical proteins of unknown structure, function, and pathogenicity. Using reliable bioinformatics tools, we attempted to analyze the MpoxV genome, identify the role of hypothetical proteins (HPs), and design a potential candidate vaccine. Out of 28, we identified seven hypothetical proteins using multi-server validation with high confidence for the occurrence of conserved domains. Their physical, chemical, and functional characterizations, including molecular weight, theoretical isoelectric point, 3D structures, GRAVY value, subcellular localization, functional motifs, antigenicity, and virulence factors, were performed. We predicted possible cytotoxic T cell (CTL), helper T cell (HTL) and linear and conformational B cell epitopes, which were combined in a 219 amino acid multiepitope vaccine with human β defensin as a linker. This multi-epitopic vaccine was structurally modelled and docked with toll-like receptor-3 (TLR-3). The dynamical stability of the vaccine-TLR-3 docked complexes exhibited stable interactions based on RMSD and RMSF tests. Additionally, the modelled vaccine was cloned in-silico in an E. coli host to check the appropriate expression of the final vaccine built. Our results might conform to an immunogenic and safe vaccine, which would require further experimental validation.Communicated by Ramaswamy H. Sarma.

Background: Despite global concerns of an opioid epidemic, there is no systematic literature review on how frequently these drugs are used in nursing home (NH) populations, including those living with dementia. Objective: This systematic review aims to describe the prevalence and incidence of opioid use in NHs. A secondary objective is to describe the use of these drugs in a subset of NH residents, namely among persons living with dementia. Methods: A systematic literature review was carried out using MEDLINE and Scopus (PROSPERO registration number CRD42021254210). Screening of title and abstract was carried out by 2 persons independently for studies published between January 1, 2011 and May 19, 2021. The main outcomes were annual prevalence, period prevalence, and duration of opioid use. Results: From a total of 178 identified studies, 29 were considered eligible for inclusion. The annual prevalence of any opioid use among all NH residents without any selection criteria ranged from 6.3% to 50% with a median annual prevalence of 22.9% (Q25-Q75: 19.5%-30.2%), based on 17 studies. Five studies measured the annual prevalence in NH residents living with dementia, finding that this ranged from 10% to 39.6%. Conclusions: More evidence is needed quantifying opioid use in NH, especially among persons living with dementia. Given that opioid use in NH is still a problem, implementation of a pain management protocol in NH or nationally would help improve clinical outcomes., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.B. has received honoraria and grant funding from Acadia Pharmaceuticals, Lundbeck, Takeda, and Axovant pharmaceutical companies, not related to this study. C.B. leads the Alzheimer’s disease psychosis (ADP) investigators group and has received honoraria from Lundbeck, Lilly, Otsuka, and Orion pharmaceutical companies, not related to this study. The other authors have no potential conflicts of interests to declare., (© The Author(s) 2023.)

Lead (Pb) is a neurotoxin, and children are vulnerable due to their evolving physiology and high-risk behaviours. Soil remediation interventions have proven effective in reducing Pb exposure. The primary objective is to measure the effectiveness of soil remediation at abandoned used lead acid battery (ULAB) recycling sites, nearby household cleaning, and community awareness in reducing blood lead levels (BLLs) in children. Additionally, this study aims to examine associations of Pb exposure with hematological, cardiovascular, renal, immunological, and endocrinological parameters in children aged 0-12 years. This study employs a quasi-experimental design, with abandoned ULAB sites as intervention sites and two control sites in Bangladesh. The intervention includes soil remediation coupled with community education. Data will be collected prior to the intervention and at a 12-month follow-up, including a comprehensive Pb exposure survey and collect environmental, turmeric samples, and blood from the child. Pb concentrations in environmental samples and turmeric samples will be determined using XRF analyser. Child BLL will be measured using Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) and proposed biochemical parameters will be analysed using routine laboratory methods. This study could provide valuable insights for designing targeted interventions in similar settings and mitigating exposure to Pb., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Deep Learning (DL) techniques have recently been used in medical image segmentation and the reconstruction of 3D anatomies of a human body. In this work, we propose a semi-supervised DL (SSDL) approach utilizing a CNN-based 3D U-Net model for femur segmentation from sparsely annotated quantitative computed tomography (QCT) slices. Specifically, QCT slices at the proximal end of the femur forming ball and socket joint with acetabulum were annotated for precise segmentation, where a segmenting binary mask was generated using a 3D U-Net model to segment the femur accurately. A total of 5474 QCT slices were considered for training among which 2316 slices were annotated. 3D femurs were further reconstructed from segmented slices employing polynomial spline interpolation. Both qualitative and quantitative performance of segmentation and 3D reconstruction were satisfactory with more than 90% accuracy achieved for all of the standard performance metrics considered. The spatial overlap index and reproducibility validation metric for segmentation-Dice Similarity Coefficient was 91.8% for unseen patients and 99.2% for validated patients. An average relative error of 12.02% and 10.75% for volume and surface area, respectively, were computed for 3D reconstructed femurs. The proposed approach demonstrates its effectiveness in accurately segmenting and reconstructing 3D femur from QCT slices., (© 2024. International Federation for Medical and Biological Engineering.)

Nivolumab is used to treat several different types of cancers. Although it is generally considered to be effective and well-tolerated, it has been associated with adverse effects requiring discontinuation of treatment, like many other drugs used for cancer. A 70-year-old male was switched from sunitinib to nivolumab for renal cell carcinoma. The patient developed persistent hypothyroidism, onycholysis, and pneumonitis at nivolumab cycle 6, 10, and 11, respectively. Using the Naranjo causality method, the likelihood of causality was deemed "probable" for pneumonitis and hypothyroidism and "possible" for onycholysis. Nivolumab was eventually discontinued due to disease progression, rather than safety concerns. Eudravigilance, the European pharmacovigilance database, was searched for all nivolumab-related individual case safety reports from Malta, up to September 4, 2023. Six reports were identified in Malta, although the 3 events identified in this case report were not reported, suggesting under-reporting in Malta. This case report identified an uncommon nivolumab adverse drug reaction (ADR), onycholysis and showed how, despite the occurrence of 3 ADRs, it was its lack of efficacy rather than its safety which led to its discontinuation in this particular patient., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To date, there is no published overview of the drug pipeline in granulomatosis with polyangiitis (GPA), a rare disease. The aim of this study was to identify clinical trials from two study repositories. A review of clinical trials was conducted using publicly available data. Clinicaltrials.gov and International Clinical Trials Registry Platform were searched from inception until 25 September 2022. Only GPA-specific studies were included; these were described in detail. A total of 137 studies were identified in the trial repositories, of which 108 (79%) studies were found to concern GPA. Of these 108 studies, 67 enrolled GPA patients to investigate pharmacotherapy in this disease (62%). Most studies included all severity types ( n  = 51; 76%); the scope of almost half of the studies was remission induction ( n  = 33; 49%). The drug class which was by the most widely investigated in trials was the non-corticosteroid immunosuppressant drug class (46; 68.7%), monoclonal antibodies (32; 47.8%), and corticosteroids (31; 46.3%). There is a need for more GPA trials to generate evidence on effectiveness in terms of severity-specificity and maintenance of remission., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Breast cancer (BC) is globally one of the leading killers among women. Within a breast tumor, a minor population of transformed cells accountable for drug resistance, survival, and metastasis is known as breast cancer stem cells (BCSCs). Several experimental lines of evidence have indicated that BCSCs influence the functionality of immune cells. They evade immune surveillance by altering the characteristics of immune cells and modulate the tumor landscape to an immune-suppressive type. They are proficient in switching from a quiescent phase (slowly cycling) to an actively proliferating phenotype with a high degree of plasticity. This review confers the relevance and impact of crosstalk between immune cells and BCSCs as a fate determinant for BC prognosis. It also focuses on current strategies for targeting these aberrant BCSCs that could open avenues for the treatment of breast carcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guha, Goswami, Sultana, Ganguly, Choudhury, Chakravarti, Bhuniya, Sarkar, Bera, Dhar, Das, Das, Baral, Bose and Banerjee.)

Introduction: During the signal detection process, statistical methods are used to identify drug-event combinations (DECs) which are disproportionately reported when compared with other drugs and events in the entire database. We hypothesise that the high volume of COVID-19 vaccine adverse drug reaction (ADR) reports transmitted to EudraVigilance may have affected the performance of disproportionality statistics used in routine signal detection, potentially resulting in signals either being masked, or false associations being flagged as potential signals., Objective: Our aim was to study the impact of COVID-19 vaccine spontaneous reporting on statistical signal detection in EudraVigilance., Methods: We recalculated the reporting odds ratio (ROR) for signals that were previously discussed at the level of the Pharmacovigilance Risk Assessment Committee, or signals that were retrieved from EudraVigilance, by omitting COVID-19 vaccine reports from the standard ROR calculation and then comparing the lower confidence interval (LCI) of the recalculated ROR to the LCI of the actual ROR in EudraVigilance., Results: In total, 52 signals for 38 active substances were reviewed. For 35 signals, the LCI of the recalculated ROR value was lower than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had a positive effect on the strength of the signal) while for 15 signals the LCI of the recalculated ROR value was higher than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had an attenuating effect on the strength of the signal). For two signals, no change in the ROR was observed. In our analysis, six significant results were found. Five DECs were found to be masked: bleomycin and immune thrombocytopenia (actual ROR LCI = 0.94, recalculated ROR LCI = 1.02), vortioxetine and heavy menstrual bleeding (actual ROR LCI = 0.3, recalculated ROR LCI = 1.06), caplacizumab and heavy menstrual bleeding (actual ROR LCI = 0.98, recalculated ROR LCI = 3.47), ziprasidone and amenorrhoea (actual ROR LCI = 0.84, recalculated ROR LCI = 1.67), and azacitidine and pericarditis (actual ROR LCI = 0.81, recalculated ROR LCI = 2.01). For the DEC of adalimumab and immune reconstitution inflammatory syndrome, the LCI of the actual ROR value was 1.14 and removing COVID-19 vaccine reporting resulted in an LCI of the recalculated ROR value of 0.94 (below threshold)., Conclusions: We demonstrated five cases of masking and one case of false-positive association due to the influence of COVID-19 vaccine spontaneous reporting on the ROR. This suggests that the high number of adverse drug reaction reports for COVID-19 vaccines in EudraVigilance has the potential to affect routine statistical signal detection activities. The impact of COVID-19 vaccine ADR reports on current signal detection practices requires further evaluation and solutions to tackle masking issues in EudraVigilance may need to be developed., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Functioning of coastal wetland habitats is essential for the ecosystem integrity and sustainability of coastal development that enables human progress along transitional waterways. However, these habitats are continuously being affected by a variety of pollutants including metallic elements. In this study, seasonal variation, pollution status and ecological risks of heavy metals (Cr, Mn, Co, Ni, As, Cu, Zn and Pb) in surface sediment of the several types of coastal wetlands (estuaries, mudflats, sandy beaches, mangroves, and saltmarshes) were detected by using X-ray fluorescence (EDXRF) spectrometry. The results showed that the mean concentration level of metals in the surficial sediment samples followed the order of Cu (84.06 ± 8.60 μg/g) > Zn (51.00 ± 8.97 μg/g) > Mn (38.25 ± 11.34 μg/g) > Cr (3.52 ± 0.91 μg/g) > Pb (0.27 ± 0.13 μg/g) > Co (0.24 ± 0.13 μg/g) > As (0.21 ± 0.12 μg/g) > Ni (0.16 ± 0.08 μg/g). In comparison to the pre-monsoon period, the post-monsoon season had higher concentrations of heavy metals while the overall accumulation level of metals in the wetlands exhibited a pattern of estuarine wetland (28.47 ± 31.35 μg/g) > mangrove (22.23 ± 30.79 μg/g) > mudflat (21.79 ± 29.71 μg/g) > sandy beach (21.47 ± 28.15 μg/g) > saltmarsh (21.28 ± 30.02 μg/g). Although, the pollution assessment indices e.g., contamination factor (CF), degree of contamination (CD), geoaccumulation index (I geo ) and pollution load index (PLI) showed minimal levels of contamination in the studied sites, enrichment factor (EF) suggested greater enrichment of the metals in the pre-monsoon season but with the lowest ecological risk (RI < 40) in both seasons. Cluster analysis, principal component analysis (PCA), and Pearson's correlation were performed to determine the sources of heavy metals in collected samples which specified that Pb, As, Co and Ni predominantly came from natural sources whereas Cu, Mn, Zn and Cr emerged from anthropogenic sources such as industrial effluents, domestic wastewater, fertilizer or pesticide consumption on farmland along the riverbank, vessel emissions, and the confluence of tributary rivers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bilal Ahamad Paray reports financial support was provided by King Saud University., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Children in low- and middle-income countries face an increased risk of impaired cognitive development due to contaminated environments, poor nutrition, and inadequate responsive stimulation from caregivers. Implementing multi-component, community-level interventions may reduce these risks; however, there is little evidence supporting implementation of these interventions at scale. We assessed the feasibility of implementing a group-based intervention that included responsive stimulation, maternal and child nutrition, water and sanitation, and childhood lead exposure prevention through the government health system in Chatmohar, Bangladesh. After implementation, we conducted 17 in-depth interviews with frontline health service providers and 12 key informant interviews with their supervisors and managers to explore the facilitators and difficulties implementing such a complex programme within the health system. Factors facilitating implementation included: high quality training and skill level of providers, support from community members, family, and supervisors, positive relationships between providers and participants, and provision of children's toys and books free of cost. Difficulties included increased workload of the providers, complicated group-based yet stage-specific delivery where providers had to manage a large group of mother-child dyads representing many different child age-groups at once, and logistics difficulties in providing toys and books through a centralised health system process. Key informants made suggestions to ensure effective government-level scale-up including engaging relevant NGOs as partners, identifying feasible ways to make toys available, and offering providers meaningful even if non-monetary rewards. These findings can be used to shape the design and delivery of multi-component child development interventions to be delivered through the health system., (© 2023 John Wiley & Sons Ltd.)

Introduction: Prescription and drug order writing are key components of patient care allowing physicians communicate their therapeutic plans. Although electronic prescriptions are becoming more common, handwritten prescriptions are still quite prevalent and a persistent issue with handwritten prescriptions is the illegibility of physician handwritings. Prescriptions have to be legible to avoid delays in healthcare provision and consequences as serious as patient death., Areas Covered: We did a scoping review of multiple articles that assessed the legibility of prescriptions in different settings (inpatient, outpatient, and pharmacies) and countries, ranging from 1997 to 2020. Studies also elaborated on possible reasons for these suboptimal prescriptions and ways to address them., Expert Opinion: While the degree of legibility of prescriptions varies widely, it remains a concern because a single incorrectly read prescription can have severe consequences. Various measures exist to possibly minimize illegible prescriptions and while none alone is probably sufficient, combining is likely to yield great results. One is the sensitization and education of physicians and physicians-in-training. Another option is audits and a third and very potent option is the use of computerized provider order entry (CPOE) system which will help improve patient safety by reducing errors due to inappropriately read prescriptions.

The major center of attraction in renewable energy technology is the designing of an efficient material for both electrocatalytic and supercapacitor (SC) applications. Herein, we report the simple hydrothermal method to synthesize cobalt-iron-based nanocomposites followed by sulfurization and phosphorization. The crystallinity of nanocomposites has been confirmed using X-ray diffraction, where crystalline nature improves from as-prepared to sulfurized to phosphorized. The as-synthesized CoFe-nanocomposite requires 263 mV overpotential for oxygen evolution reaction (OER) to reach a current density of 10 mA/cm 2 whereas the phosphorized requires 240 mV to reach 10 mA/cm 2 . The hydrogen evolution reaction (HER) for CoFe-nanocomposite exhibits 208 mV overpotential at 10 mA/cm 2 . Moreover, the results improved after phosphorization showing 186 mV to reach 10 mA/cm 2 . The specific capacitance (C sp ) of as-synthesized nanocomposite is 120 F/g at 1 A/g, along with a power density of 3752 W/kg and a maximum energy density of 4.3 Wh/kg. Furthermore, the phosphorized nanocomposite shows the best performance by exhibiting 252 F/g at 1 A/g and the highest power and energy density of 4.2 kW/kg and 10.1 Wh/kg. This shows that the results get improved more than twice. The 97% capacitance retention after 5000 cycles shows cyclic stability of phosphorized CoFe. Our research thus offers cost-effective and highly efficient material for energy production and storage applications., (© 2023. The Author(s).)

The obesity epidemic is not only limited to high-income or urbanized societies, but has also become prevalent among rural communities, even in India. Approaches to modifiable behaviors, like unhealthy dietary habits or a sedentary lifestyle, could bring positive results among obese populations. This research aimed to assess the effectiveness of lifestyle intervention programs to prevent obesity and cardio-metabolic risks among Bengali obese adults (Body Mass Index of 25-30kg/m 2 ). The population was selected from rural and urban communities of Hooghly district in west Bengal, India and included 121 participants (20-50 years), divided into four groups (rural male, rural female, urban male, and urban female) who underwent a 12-month intervention program. Anthropometric parameters, systolic and diastolic blood pressure, biochemical parameters (fasting blood glucose, fasting plasma insulin, Homeostatic Model Assessment for Insulin Resistance [HOMA-IR] and lipid profile), dietary habits, and physical activity profiles were assessed before the study (baseline), after 12 months of intervention (post-intervention), and after 24 months (follow-up), among all groups, to evaluate changes in data within and between the groups (rural vs. urban). The results showed a significant decline in anthropometric parameters and fasting blood glucose levels among all intervention groups, HOMA-IR in rural females, and serum triglyceride levels in urban groups. A significant improvement was noted regarding dietary habits and physical activity, even during follow-up. The impact of the intervention program did not show any rural-urban difference. The lifestyle intervention program was effective in reducing obesity and related health risks and promoting a healthy lifestyle among the target population., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Background: Medication error is a common cause of patient harm. The study aims to propose a way to manage the risk of medication errors in a novel way, by identifying practice areas where mitigating patient harm should be prioritized using a risk management approach., Methods: Suspected Adverse Drug Reactions (sADRs) in Eudravigilance database over three years were reviewed to identify preventable medication errors. These were classified using a new method based upon the root cause underlying pharmacotherapeutic failure. The correlation between severity of harm and type of medication error, and other clinical parameters was investigated., Results: Overall, 2294 medication errors were identified from Eudravigilance, of which 1300 (57%) were due to pharmacotherapeutic failure. Most cases of preventable medication error involved prescribing (41%) and administration (39%). The variables which significantly predicted severity of medication errors were pharmacological group, patient age, number of drugs prescribed, and route of administration. The drug classes most strongly associated with harm included cardiac drugs, opioids, hypoglycaemics, antipsychotics, sedatives, and antithrombotic agents., Conclusion: The findings of this study highlight the feasibility of using a novel conceptual framework to identify areas of practice at risk of pharmacotherapeutic failure where Interventions by healthcare professionals in these areas are most likely to improve medication safety.

Introduction: Migraine is common in females of childbearing age and negatively impacts quality of life. The majority of those with migraine who become pregnant see an improvement in their condition but not all do. Providing evidence-based recommendations for the pharmacological management of migraine in pregnancy is challenging., Areas Covered: This narrative review provides an update on the safety of drugs used for migraine in pregnancy. National and international guidelines on the management of episodic migraine in adults were used to select the drugs of relevance to pregnant women. The final list of drugs was chosen by a pain specialist who categorized them according to drug class and use in acute management or prevention. PubMed was searched from inception to 31st July 2022 for evidence on drug safety., Expert Opinion: Obtaining high-quality drug safety data in pregnant migraineurs is difficult not least because exposing a fetus to research-related risks is often considered unethical. There is reliance on observational studies which often group drugs together and lack specificities pertinent to drug prescribing like timing, dosing and duration. Improved statistical tools, study designs and the creation of international collaborative frameworks are ways to advance knowledge on drug safety in pregnancy.

Background: Reliable and valid measurement of early child development are necessary for the design of effective interventions, programs, and policies to improve early child outcomes. One widely used measure in low- and middle-income countries (LMICs) is the Bayley Scales of Infant and Toddler Development III (Bayley-III). Alternatively, the Bangladeshi-adapted Ages and Stages Questionnaire Inventory (ASQ:I) can be administered more quickly, inexpensively, and with less training than the Bayley-III. We aimed to assess the concurrent validity of the Bangladeshi-adapted ASQ:I with the Bayley-III in children 4-27 months old in rural Bangladesh., Methods: The sample was a sub-sample (n = 244) of endline participants from an evaluation of an early child development intervention (July-August 2018). We assessed concurrent validity between internally age-standardized domain-specific and total scores using Pearson correlations both overall and stratified by age and intervention status. We also assessed correlations between scores and variables theoretically related to child development including maternal education and stimulation in the home., Results: The overall correlation between ASQ:I and Bayley-III total scores was moderate (r = 0.42 95% CI: 0.30-0.53), with no systematic differences by intervention status. Overall, concurrent validity was highest for the gross motor domain (r = 0.51, 0.40-0.60), and lowest for the fine motor domain (r = 0.20, 0.04-0.33). Total ASQ:I and Bayley-III scores were positively correlated with child stimulation and maternal education., Conclusion: The Bangladeshi-adapted ASQ:I is a low-cost tool that can be feasibly administered in rural Bangladesh, is moderately correlated with the Bayley-III, and can be used to measure child development when human, time, or financial resources are constrained., (© 2023. The Author(s).)

The exponential rise of healthcare problems like human aging and road traffic accidents have developed an intrinsic challenge to biomedical sectors concerning the arrangement of patient-specific biomedical products. The additively manufactured implants and scaffolds have captured global attention over the last two decades concerning their printing quality and ease of manufacturing. However, the inherent challenges associated with additive manufacturing (AM) technologies, namely process selection, level of complexity, printing speed, resolution, biomaterial choice, and consumed energy, still pose several limitations on their use. Recently, the whole world has faced severe supply chain disruptions of personal protective equipment and basic medical facilities due to a respiratory disease known as the coronavirus (COVID-19). In this regard, local and global AM manufacturers have printed biomedical products to level the supply-demand equation. The potential of AM technologies for biomedical applications before, during, and post-COVID-19 pandemic alongwith its relation to the industry 4.0 (I4.0) concept is discussed herein. Moreover, additive manufacturing technologies are studied in this work concerning their working principle, classification, materials, processing variables, output responses, merits, challenges, and biomedical applications. Different factors affecting the sustainable performance in AM for biomedical applications are discussed with more focus on the comparative examination of consumed energy to determine which process is more sustainable. The recent advancements in the field like 4D printing and 5D printing are useful for the successful implementation of I4.0 to combat any future pandemic scenario. The potential of hybrid printing, multi-materials printing, and printing with smart materials, has been identified as hot research areas to produce scaffolds and implants in regenerative medicine, tissue engineering, and orthopedic implants., Competing Interests: Conflict of interestAuthors declare no conflict of interest or personal relationships that could have appeared to influence this work., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, corrected publication 2023Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Transforming growth factor beta induced ( TGFBI ) gene mutations have been reported as the cause of a group of genetically inherited, visually debilitating, corneal dystrophies (CD). A scoping literature review to identify and categorize compounds that inhibit corneal TGFBI expression and/or promote TGFBIp degradation was performed. Emphasis was given to their potential to be used as a cost-effective approach via drug repurposing., Areas Covered: We performed a thorough search of original peer-reviewed literature using electronic bibliographic databases and selected articles according to a set of criteria. The total number of articles retrieved from the search terms applied to the databases was 2344. The number of relevant full-text articles included added up to 19. We identified 16 compounds that can theoretically reduce the levels of mutant TGFBIp in human corneal cells., Expert Opinion: Currently, the only temporary treatments available for this condition are lubricant drops and surgery. Here, we explored the crosstalk between cascades that regulate TGFBI expression and identified compounds that target these pathways. Compounds that inhibit DNA synthesis and function, increase elimination of TGFBIp or bind to mutant TGFBIp were also explored with the aim of highlighting promising compounds that can be used in future cost-effective drug-repurposing studies.

Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson's disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia., (© 2022. The Author(s).)

Extent of metastasis influences activation of platelets in tumor-microenvironment. Activated platelets potentiate mesenchymal-stem-cells (MSCs) to migrate in secondary metastatic sites without participation in process of invasion. Presence of higher percentage of MSCs along with activated-platelets induces formation of vascular-mimicry (VM). The pathophysiology, VM, has already been reported in multiple types of cancer including lung, ovary, melanoma etc. and related to poor-prognosis. Interaction of MSCs with platelets in cell-to-cell contact dependent manner is essential for their migration, thereby, VM. Evidences are obtained suggesting that under influence of tumor-associated-activated-platelets, expressions of vimentin, ve-cadherin are increased, along with decrease in e-cadherin on CD105 + MSCs in both mRNA and protein levels that may help in formation of vessel like structure in VM. Adoptive transfer of MSCs along with tumor-activated-platelets causes greater B16 melanoma metastasis at lungs in comparison to MSCs with non-activated platelets. Presence of CD105 + Vimentin + MSCs in vessel like structure in the metastatic lung confirms the involvement of platelet-activated-MSCs in VM, thereby, in metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC) and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMI of >40 kg/m 2 and >35 kg/m 2 with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Zaman et al.)

Acute promyelocytic leukemia (APML) is defined as a balanced chromosomal translocation between chromosomes 15 and 17 t(15;17)(q24;q21), which results in the formation of promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) fusion protein. A widespread recommendation for APML treatment is combined all-trans retinoic acid (ATRA)/arsenic trioxide (ATO) therapy. Differentiation syndrome (DS), or retinoic acid syndrome, is one of the well-known complications of APML treated with ATRA or ATO. The presenting symptoms of APML-induced DS are diverse, and rare symptoms are easily misdiagnosed. However, unexplained fever, dyspnea, weight gain > 5 kg, leukocytosis, acute renal failure, and a chest radiograph demonstrating pleural or pericardial effusion are the most common manifestations of DS. Early recognition and prompt initiation of corticosteroids are key factors in the management of DS. As soon as ATRA/ATO therapy is started, prophylactic treatment with steroids has been recommended to minimize the severity of DS. It is proposed that ATRA/ATO should be stopped or held once the signs and symptoms of DS develop. This case report describes a 45-year-old male who was diagnosed with APML after he developed episodes of hematuria and nose bleeding at home. The patient was also given an empiric steroid along with ATRA/ATO to lessen the intensity of DS. Our study suggests that early initiation of prophylactic steroid treatment can improve the prognosis and mortality of patients with APML-induced DS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sultana et al.)

Acromegaly is a rare disease characterized by an excessive production of growth-hormone and insulin-like growth factor 1, typically resulting from a GH-secreting pituitary adenoma. This study was aimed at comparing and measuring accuracy of newly and previously developed coding algorithms for the identification of acromegaly using Italian claims databases. This study was conducted between January 2015 and December 2018, using data from the claims databases of Caserta Local Health Unit (LHU) and Sicily Region in Southern Italy. To detect acromegaly cases from the general target population, four algorithms were developed using combinations of diagnostic, surgical procedure and co-payment exemption codes, pharmacy claims and specialist's visits. Algorithm accuracy was assessed by measuring the Youden Index, sensitivity, specificity, positive and negative predictive values. The percentage of positive cases for each algorithm ranged from 7.9 (95% CI 6.4-9.8) to 13.8 (95% CI 11.7-16.2) per 100,000 inhabitants in Caserta LHU and from 7.8 (95% CI 7.1-8.6) to 16.4 (95% CI 15.3-17.5) in Sicily Region. Sensitivity of the different algorithms ranged from 71.1% (95% CI 54.1-84.6%) to 84.2% (95% CI 68.8-94.0%), while specificity was always higher than 99.9%. The algorithm based on the presence of claims suggestive of acromegaly in ≥ 2 different databases (i.e., hospital discharge records, copayment exemptions registry, pharmacy claims and specialist visits registry) achieved the highest Youden Index (84.2) and the highest positive predictive value (34.8; 95% CI 28.6-41.6). We tested four algorithms to identify acromegaly cases using claims databases with high sensitivity and Youden Index. Despite identifying rare diseases using real-world data is challenging, this study showed that robust validity testing may yield the identification of accurate coding algorithms., (© 2022. The Author(s).)

Background: While the prevalence of undernutrition in children has decreased in many low- and middle-income countries since the 1990s, prevalences of overweight and obesity have increased. Frequent consumption of sugar-sweetened food might have contributed to this change, although very little is known about sugar-sweetened food consumption in early life., Objectives: The objective of this study was to explore the associations between individual, household, and maternal factors and the prevalence of sugar-sweetened food consumption in 6- to 24-month-old children in Bangladesh., Methods: Multistage sampling was used to select households with children aged 6-24 months in rural Chatmohar, a subdistrict of Bangladesh (n = 1635). Research assistants conducted a 24-hour qualitative dietary recall questionnaire with the enrolled child's primary caregiver to measure maternal and child dietary patterns. We examined factors associated with the prevalence of child sugar-sweetened food consumption with multivariate logistic regression models. We conducted tests of heterogeneity to explore differential associations between the child sugar-sweetened food consumption prevalence and household income by maternal nutrition knowledge and wealth., Results: Primary caregivers reported that 62% of toddlers had consumed sugar-sweetened food in the past 24 hours. A higher prevalence of child sugar-sweetened food consumption was associated with both a higher dietary diversity score (OR, 1.19; 95% CI, 1.09-1.29) and a higher prevalence of maternal sugar-sweetened food consumption (OR, 2.54; 95% CI, 1.97-3.28). At higher levels of maternal nutrition knowledge and wealth, more household income was associated with a lower prevalence of child sugar-sweetened food consumption., Conclusions: Almost two-thirds of 6- to 24-month-old children in rural Chatmohar, Bangladesh, had consumed sugar-sweetened food in the last day. This is a high and concerning prevalence, and the associated factors identified in this study should be investigated further to identify potential areas of intervention to decrease the prevalence of child sugar consumption in Bangladesh., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Describe drug utilisation and clinical outcomes of intravitreal anti-VEGF drug and dexamethasone use in the real-world setting in Southern Italy using data from multi-centre study of retinal disease. Clinical data of retinal disease patients treated with anti-VEGF drugs and dexamethasone implant in 6 out-patient ophthalmology centres from Southern Italy were collected by means of an electronic case report form. Patients receiving at least one intravitreal injection/implant of the study drugs were followed for up to two years and described in terms of demographics and clinical characteristics. Drug utilisation patterns were described. A sign-rank test was used to compare clinical data on visual acuity and other ophthalmic parameters from baseline at different follow-up times for each indication. Data from 1327 patients was collected. Most patients were diagnosed with age-related macular degeneration (AMD) (660, 49.7%), followed by diabetic macular oedema (423, 31.9%), retinal vein occlusion (164, 12.3%), and myopic choroidal neovascularization (80, 6.0%). Patients were followed for a median of 10.3 months (interquartile range: 3.6 - 24.7 months). Mean patient age was 69.7 (±10.9) years and 54.2% were males. Ranibizumab (55.4%) and aflibercept (27.5%) were the most commonly used drugs. Baseline visual acuity significantly improved by about 0.05 to 0.1 logMAR at all follow-up times for AMD and RVO but less consistently for the other diseases. Intravitreal ranibizumab use accounted for half of all treatment for retinal diseases in a Southern Italian out-patient setting. Patients treated with anti-VEGF drugs for AMD and RVO in Southern Italy experienced significant improvement in VA.

Introduction: This study aimed to establish which worldwide population cohorts have a genetic make-up closest to that of a large sample of the Maltese population with regard to corneal dystrophy (CD) genes., Methods: Single nucleotide polymorphisms (SNPs) in the Maltese cohort were compared with worldwide cohorts. Fixation index (F ST ) values were calculated to evaluate population differentiation. The genetic prevalence of CD subtypes in worldwide and Maltese cohorts were calculated, and single nucleotide missense mutations present in the Maltese cohort were evaluated for potential pathogenicity., Results: F ST values showed that CD-related genes differ substantially among the studied cohorts. F ST values for each SNP showed greatest differentiation between the Maltese and African cohorts and least differentiation with the Puerto Rican, Mexican, and Colombian cohorts. One TGFBI casual CD mutation, 502V, which causes a Bowman's layer CD/atypical Thiel-Behnke CD was identified in the Maltese cohort. The KRT3 NC&#95;000012.11:g.53186088G>C mutation was potentially deleterious., Conclusion: Identifying populations with least genetic differentiation can facilitate and help guide future diagnostic and treatment strategies for Maltese individuals with CDs in the absence of comparable Maltese data. Analysing the previously unknown CD genetic pool present in a large Maltese cohort adds to the global genetic bank that researchers rely on for medical progress., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Groundwater aquifers are a common source of drinking water in Bangladesh. However, groundwater contamination is a major public health concern across the country. This research aims to examine the groundwater quality and health concerns using a random sampling process. Multivariate statistical and health risk analyses of elements were performed to determine the source of contaminants and their effects on human health. A total of 24 parameters were analyzed, where Na + , NH 4 + , K + , Mg 2+ , F - , NO 3 - , Mn, Fe, Se, U, and As concentrations were found to be high in different sampling points compared to the Department of Environment of Bangladesh (DoE), and the World Health Organization (WHO) groundwater quality standards. Principal Component Analysis (PCA) and Cluster Analysis (CA) identified the dominant and potential sources of contaminants in the groundwater aquifer, including geogenic, salinity intrusion, industrial, and agricultural. The results of the degree of contamination level (C d ) and the heavy metal pollution index (HPI) showed that 28% and 12% of the sampling points had high levels of heavy metal contamination, indicating a high risk for human health issues. Cr concentrations were found to have a higher carcinogenic (cancer) risk than As and Cd concentrations. Hazard quotient (HQ) and hazard index (HI) scores expressed the hazardous status and possible chronic effects in the context of individual sampling points. For both child and adults, 44% and 36% of the sampling points had a high HI score, indicating the possibility of long-term health risks for local populations., (Copyright © 2022. Published by Elsevier B.V.)

Esophageal cancer is the sixth leading cause of cancer death, and esophageal squamous cell carcinoma (ESCC) is the most prevalent type worldwide, with a poor prognosis due to late diagnosis. The search for new molecular prognostic biomarkers revealed that dysregulation of anaphase promoting complex/cyclosome (APC/C) activation due to altered expression of APC molecules might lead to perturbed mitotic progression leading to malignancy. We analyzed the expression of the four different subunits of the APC/C complex-APC3, APC4, APC5 and APC7-by Real Time Polymerase Chain Reaction (RT-PCR). The findings were then correlated with clinicopathological parameters and different lifestyle factors. Significant upregulation of APC7 (tissue and blood: N = 50; 3.72 ± 1.21 and 4.45 ± 1.18, respectively) and APC3 (tissue and blood: N = 52 and 55 and 4.50 ± 1.41 and 4.58 ± 1.06, respectively) suggests their role in uncontrolled cell proliferation. In addition to their association with increasing age, their significant association with tumor size, node stage (only APC7 (p < 0.05)), and dysphagia grade supports a potential role in tumorigenic transformation in ESCC. Furthermore, several exclusive lifestyle-associated factors play a crucial supporting role in the development of ESCC in the Northeast Indian population. Various lifestyle factors, such as the duration of smoking, tobacco and betel nut consumption, and the duration of alcohol consumption, are significantly associated with the expression of APC. Analysis based on Pearson's correlation coefficient indicated a positive correlation among the gene expression levels ofAPC3 (both blood and tissue), APC5 (tissue) and APC3 (tissue), APC7 (tissue) and APC3 (tissue), and APC7 (tissue) and APC3 (blood). Additionally, a positive correlation was found between APC7 expression in blood and tissue samples. However, no significant correlation was found between APC 7 expression and APC4 and APC5 expression in either blood or tissue samples., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Background: The use of chemical pesticides in developing countries like Bangladesh and their impacts on human health and food security is a global concern. Bangladesh is an agricultural dependent country for the growing population demand for food security and food safety. We conduct this study to assess public health threats of commonly utilised pesticides including malathion and nitrobenzene in female rabbit model., Methods: Thirty New Zealand White healthy rabbit was divided randomly into three groups; and subjected to distilled water as control, malathion@ 5 mg/kg body weight and nitrobenzene@ 5 mg/kg body i.p daily for the next 15 days. Hematology, serum biochemistry and hormonal assay were performed., Results: Red blood cell (RBC) concentrations (TEC, Hb, PCV%) were reduced in rabbits exposed to malathion and nitrobenzene. The neutrophil and eosinophil percentage were increased in the malathion and nitrobenzene exposed juvenile rabbit group. We found that serum aspartate aminotransferase (AST) and creatinine were increased in the nitrobenzene exposed group in infants, whereas malathion exposure increased serum alanine aminotransferase (ALT). In contrast, the juvenile group exposed to malathion increased the ALT level. There was no change in AST or creatinine levels in juvenile rabbits exposed to malathion or nitrobenzene. Serum estradiol levels were significantly lower in rabbits exposed to malathion and nitrobenzene. Serum testosterone concentration was increased in juvenile rabbits exposed to malathion and nitrobenzene, but progesterone was decreased in malathion exposed juvenile rabbits., Conclusion: However, this study highlights the importance of rigorous monitoring and testing of agricultural products. In addition, strengthen research and extension in the fields of agro economy, organic farming, local universities and farmer associations., (© 2022. The Author(s).)

Stroke is one of the major health problems with major disability and loss of daily life. Serum ferritin damages the ischemic part of the brain by production of free radicals. The generation of free radical hydroxyl is catalyzed by iron released from the intracellular stores like ferritin during ischemia. Increase in ferritin may also cause progression of stroke by enhancing the release of glutamate from the brain cells. Glutamate triggers biochemical reactions that lead to brain cell death including the production of free radical in the brain tissue. The inflammatory marker ferritin has gained clinical interest as a prognostic marker in acute ischemic stroke., Material: The study was a hospital based cross sectional study conducted in 100 consecutive cases of acute ischemic stroke meeting the selection criteria. Serum ferritin was measured as soon as patient got admitted in the hospital. National Institute of Health Stroke Scale(NIHSS) scoring was applied at the time of admission and these patients were grouped into mild, moderate and severe. Modified Rankin Scale(MRS) was applied to know the recovery of the patients after 4 weeks., Observation: The minimum and maximum mean values of serum ferritin in the study were 31.7 and 511.5 respectively, with an average mean of 328.33. 61(61%) cases had high serum ferritin values and 39 (39%) cases had normal serum ferritin. Among the 61 cases having high serum ferritin levels, 26 (40%) were in moderate category and 35(60%) were in severe category of NIHSS. On the other hand, among the remaining 39 cases who had normal serum ferritin, all the 39 cases come under moderate group and none in severe group. Out of 61 cases with high serum ferritin, 12 cases were in good outcome category and 49 cases in poor outcome category of MRS scores., Conclusion: Pearson's r correlation reveals positive correlation between serum ferritin and NIHSS score(p value =0.00001). Pearson's r correlation analysis also reveals positive correlation between serum ferritin and MRS (p value =0.00001). The patients with higher serum ferritin levels at admission tend to deteriorate more when compared to patients with normal levels. Thus serum ferritin can be used as a prognostic marker in acute ischemic stroke patients., (© Journal of the Association of Physicians of India 2011.)

Water splitting using renewable energy resources is an economic and green approach that is immensely enviable for the production of high-purity hydrogen fuel to resolve the currently alarming energy and environmental crisis. One of the effective routes to produce green fuel with the help of an integrated solar system is to develop a cost-effective, robust, and bifunctional electrocatalyst by complete water splitting. Herein, we report a superhydrophilic layered leaflike Sn 4 P 3 on a graphene-carbon nanotube matrix which shows outstanding electrochemical performance in terms of low overpotential (hydrogen evolution reaction (HER), 62 mV@10 mA/cm 2 , and oxygen evolution reaction (OER), 169 mV@20 mA/cm 2 ). The outstanding stability of HER at least for 15 days at a high applied current density of 400 mA/cm 2 with a minimum loss of potential (1%) in acid medium infers its potential compatibility toward the industrial sector. Theoretical calculations indicate that the decoration of Sn 4 P 3 on carbon nanotubes modulates the electronic structure by creating a higher density of state near Fermi energy. The catalyst also reveals an admirable overall water splitting performance by generating a low cell voltage of 1.482 V@10 mA/cm 2 with a stability of at least 65 h without obvious degradation of potential in 1 M KOH. It exhibited unassisted solar energy-driven water splitting when coupled with a silicon solar cell by extracting a high stable photocurrent density of 8.89 mA/cm 2 at least for 90 h with 100% retention that demonstrates a high solar-to-hydrogen conversion efficiency of ∼10.82%. The catalyst unveils a footprint for pure renewable fuel production toward carbon-free future green energy innovation.

The coronavirus disease 2019 (COVID-19) infection has most commonly led to patients presenting with pulmonary disease, including severe acute respiratory syndrome. However, in about 14-53% of patients with a newly diagnosed COVID-19 infection, the liver is the organ most drastically affected, as opposed to the lungs. In patients with preexisting liver damage, the first symptom of a COVID-19 infection may come from worsening liver failure such as hepatic encephalopathy or worsening ascites. This case report highlights this unusual presentation of a COVID-19 infection in a patient with preexisting alcoholic liver cirrhosis. We report this case to heed warning that acutely worsening liver failure may be the first presenting symptom of a superimposed COVID-19 infection on preexisting liver disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Chowdhury et al.)

Introduction: It is generally acknowledged that the ocular safety profile of intravitreal anti-VEGF drugs is acceptable, while the burden of systemic safety of these intravitreal agents is still being debated. The evaluation of the systemic safety of these drugs using real-world data (RWD), such as spontaneous reporting systems (SRS), electronic medical records (EMRs) and claims databases has several advantages, including the capture of outcomes among real-world populations over long observation periods. Nevertheless, there is a relatively small body of research exploring the post-marketing safety of these drugs., Areas Covered: The aim of this scoping review is to outline and discuss some of the methodological challenges to be faced when investigating the systemic safety of intravitreal anti-VEGF drugs using different sources of RWD., Expert Opinion: Such challenges include the selection of the most suitable data source, taking into account how well drug utilization is captured and whether the outcomes and covariates of interest can be captured. The strengths and limitations of some analytic methods that can be used to quantify risk, such as the intention-to-treat approach and the as-treated approach, complement each other, and using these together provides a more balanced analysis.

The decision-making process and the information flow from physicians to patients regarding deliveries through cesarean section (C-section) has not been adequately explored in Bangladeshi context. Here, we aimed to explore the extent of information received by mothers and their family members and their involvement in the decision-making process. We conducted a qualitative exploratory study in four urban slums of Dhaka city among purposively selected mothers ( n = 7), who had a cesarean birth within one-year preceding data collection, and their family members ( n = 12). In most cases, physicians were the primary decision-makers for C-sections. At the household level, pregnant women were excluded from some crucial steps of the decision-making process and information asymmetry was prevalent. All interviewed pregnant women attended at least one antenatal care visit; however, they neither received detailed information regarding C-sections nor attended any counseling session regarding decisions around delivery type. In some cases, pregnant women and their family members did not ask health care providers for detailed information about C-sections. Most seemed to perceive C-sections as risk-free procedures. Future research could explore the best ways to provide C-section-related information to pregnant women during the antenatal period and develop interventions to promote shared decision-making for C-sections in urban Bangladeshi slums.

Two-dimensional (2D) transition-metal carbides (MXenes) are emerging as promising materials for a wide range of applications owing to their intriguing electrical, optical, and optoelectronic properties. However, the modulation of metallic Ti 3 C 2 T x MXene electronic properties is the key challenge to fabricate functional nanoelectronic devices. Here, we demonstrate a solution-processable route to fabricate Ti 3 C 2 T x MXene/CuI nanoparticle heterointerfaces by employing a layer-by-layer assembly process. The charge transfer at the heterointerfacial assembly is monitored qualitatively from the quenched photoluminescence emission of CuI. The stable electrical conductivity and consistent Raman spectra of the 3-LBL assembly (three sequential stacks of CuI/MXene) signify the oxidation stability of Ti 3 C 2 T x thin films even after exposure to the ambient environment for 2 months. Furthermore, the 3-LBL assembly exhibited a three-dimensional (3D) variable-range hopping-based electrical conduction in the temperature range 2 ≤ T < 100 K, contrary to the weak localized transport phenomenon in Ti 3 C 2 T x MXene. The difference in charge transport mechanism is supported by distinct magnetoresistance (MR) of the Ti 3 C 2 T x MXene (negative MR, -0.4%) and 3-LBL assembly (positive MR, 1.6%). Therefore, the modulated electrical transport and superior oxidation stability of the Ti 3 C 2 T x MXene in the 3-LBL assembly have the potential to develop next-generation optoelectronic and memory devices.

In low- and middle-income countries, most latrines are not accessible to young children. We explored how to modify existing pit latrines to make them child friendly. We conducted four focus group discussions with mothers to explore barriers to child latrine use. We then enrolled 20 households with a child aged 3-7 years old to test six enabling technologies developed based on the identified barriers. Two to three weeks after installing the selected enabling technologies in each household, researchers conducted 19 in-depth interviews with caregivers to explore the technologies' acceptance and feasibility. Common barriers included the discomfort of squatting on a large pan, fear of darkness, and fear of a slippery floor. Of the potential solutions, a ring to stabilize the child while squatting in the latrine was preferred by children and was affordable and available. A wooden board with a smaller hole than the usual pan reduced fears of falling and helped eliminate discomfort but was inconvenient to handle and clean. A transparent fiberglass roof tile was affordable, available, increased visibility, and kept the latrine floor dry. In conclusion, the fiberglass roof tile and stability ring were two affordable and locally available technologies that facilitated latrine use by children aged 3-7 years.

Background: Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs., Methods: MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool., Results: Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk., Conclusions: This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients., (© 2021. The Author(s).)

Early child development has been influenced directly and indirectly by the COVID-19 pandemic, and these effects are exacerbated in contexts of poverty. This study estimates effects of the pandemic and subsequent population lockdowns on mental health, caregiving practices, and freedom of movement among female caregivers of children 6-27 months (50% female), in rural Bangladesh. A cohort (N = 517) was assessed before and during the pandemic (May-June, 2019 and July-September, 2020). Caregivers who experienced more food insecurity and financial loss during the pandemic reported larger increases in depressive symptoms (0.26 SD, 95% CI 0.08-0.44; 0.21 SD, 0.04-0.40) compared to less affected caregivers. Stimulating caregiving and freedom of movement results were inconsistent. Increases in depressive symptoms during the pandemic may have consequences for child development., (© 2021 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Lead exposure is harmful at any time in life, but pre-natal and early childhood exposures are particularly detrimental to cognitive development. In Bangladesh, multiple household-level lead exposures pose risks, including turmeric adulterated with lead chromate and food storage in lead-soldered cans. We developed and evaluated an intervention to reduce lead exposure among children and their caregivers in rural Bangladesh. We conducted formative research to inform theory-based behavioral recommendations. Lead exposure was one of several topics covered in the multi-component intervention focused on early child development. Community health workers (CHWs) delivered the lead component of the intervention during group sessions with pregnant women and mother-child dyads (<15 months old) in a cluster-randomized trial. We administered household surveys at baseline (control n = 301; intervention n = 320) and 9 months later at endline (control n = 279; intervention n = 239) and calculated adjusted risk and mean differences for primary outcomes. We conducted two qualitative assessments, one after 3 months and a second after 9 months, to examine the feasibility and benefits of the intervention. At endline, the prevalence of lead awareness was 52 percentage points higher in the intervention arm compared to the control (adjusted risk difference: 0.52 [95% CI 0.46 to 0.61]). Safe turmeric consumption and food storage practices were more common in the intervention versus control arm at endline, with adjusted risk differences of 0.22 [0.10 to 0.32] and 0.13 [0.00 to 0.19], respectively. Semi-structured interviews conducted with a subset of participants after the intervention revealed that the perceived benefit of reducing lead exposure was high because of the long-term negative impacts that lead can have on child cognitive development. The study demonstrates that a group-based CHW-led intervention can effectively raise awareness about and motivate lead exposure prevention behaviors in rural Bangladesh. Future efforts should combine similar awareness-raising efforts with longer-term regulatory and structural changes to systematically and sustainably reduce lead exposure., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Beta-thalassemia is an autosomal recessive hereditary anemia characterized by reduced or absent β-globin chain synthesis, affecting about 60,000 people peryear. Management for β-thalassemia major includes regular blood transfusions followed by iron chelating therapy and drug targeting ineffective erythropoiesis. Areas covered: The safety of licensed drugs for the management of β-thalassemia is reviewed, using evidence from clinical trials and observational research. Such drugs include the iron chelators and the erythrocyte maturation agent luspatercept. The safety of emerging treatment, such as hydroxyurea and thalidomide is also reviewed. Expert opinion : Beta-thalassemia is arare disease, and is not surprising that there are limited studies investigating the safety of drugs used in this disease. Indeed, although observational studies are the main source of drug safety information in areal-world setting, only eleven studies were identified for iron-chelators and none of these estimated the risk of agiven safety outcome. Future work should aim to better leverage existing sources of real-world datato investigate drug safety in thalassemia.

Community Health Workers (CHWs) can effectively implement maternal and child health interventions, but there is paucity of evidence on how to integrate child stimulation into these interventions, and their delivery at scale. In rural Bangladesh, CHWs implemented an intervention integrating psychosocial stimulation, nutrition, maternal mental health, water, sanitation, hygiene (WASH) and lead exposure prevention. In each of 16 intervention villages, one CHW worked with 20 households. CHWs bi-weekly held group meetings or alternated group meetings and home visits with pregnant women and lactating mothers. We assessed the intervention through five focus groups, four interviews and one group discussion with CHWs and their supervisors to explore success factors of implementation. CHWs' training, one-on-one supervision and introduction by staff to their own community, and adoption of tablet computers as job aids, enabled successful session delivery to convey behavioral recommendations. CHWs reported difficulties delivering session due to the complexity of behavioral recommendations and struggled with age-specific intervention material. Young children's attendance in group sessions generated distractions that undermined content delivery. We identified ways to minimize the difficulties to strengthen intervention-delivery during implementation, and scale-up. Iterative revisions of similarly integrated interventions based on qualitative evaluation findings could be delivered feasibly by CHWs and allow for implementation at scale.