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Abstract Background Community engagement (CE) interventions include a range of approaches to involve communities in the improvement of their health and wellbeing. Working with communities defined by location or some other shared interest, these interventions may be important in assisting equity and reach of communicable disease control (CDC) in low and lower-middle income countries (LLMIC). We conducted an umbrella review to identify approaches to CE in communicable disease control, effectiveness of these approaches, mechanisms and factors influencing success. Methods We included systematic reviews that: i) focussed on CE interventions; ii) involved adult community members; iii) included outcomes relevant to communicable diseases in LLMIC; iv) were written in English. Quantitative results were extracted and synthesised narratively. A qualitative synthesis process enabled identification of mechanisms of effect and influencing factors. We followed guidance from the Joanna Briggs Institute, assessed quality with the DARE tool and reported according to standard systematic review methodology. Results Thirteen systematic reviews of medium-to-high quality were identified between June and July 2017. Reviews covered the following outcomes: HIV and STIs (6); malaria (2); TB (1); child and maternal health (3) and mixed (1). Approaches included: CE through peer education and community health workers, community empowerment interventions and more general community participation or mobilisation. Techniques included sensitisation with the community and involvement in the identification of resources, intervention development and delivery. Evidence of effectiveness of CE on health outcomes was mixed and quality of primary studies variable. We found: i) significantly reduced neonatal mortality following women’s participatory learning and action groups; ii) significant reductions in HIV and other STIs with empowerment and mobilisation interventions with marginalised groups; iii) significant reductions in malaria incidence or prevalence in a small number of primary studies; iv) significant reductions in infant diarrhoea following community health worker interventions. Mechanisms of impact commonly occurred through social and behavioural processes, particularly: changing social norms, increasing social cohesion and social capacity. Factors influencing effectiveness of CE interventions included extent of population coverage, shared leadership and community control over outcomes. Conclusion Community engagement interventions may be effective in supporting CDC in LLMIC. Careful design of CE interventions appropriate to context, disease and community is vital.

Competing Interests: The authors have no conflicts of interest to declare.

Background: There are no randomized data to inform the extent to which transvenous cardiac leads cause tricuspid regurgitation (TR)., Objectives: This study sought to determine the effect of a transvenous implantable cardioverter-defibrillator (TV-ICD) on TR severity, and secondarily, on right ventricular (RV) size and function., Methods: We evaluated TR severity before and 6 months after implantable cardioverter-defibrillator insertion in a post hoc analysis of adults randomized to receive a transvenous (n = 252) or subcutaneous implantable cardioverter-defibrillator (S-ICD) (n = 251) device. TR and RV size and systolic function were assessed by echocardiographic images analyzed in a core laboratory., Results: At baseline, at least mild TR was present in 30% of individuals. At 6 months, the proportion of participants with any TR in the TV-ICD group was 42% vs 19% in the S-ICD group (P < 0.001). The proportion with moderate or severe TR was 7% in the TV-ICD group vs 2% in the S-ICD group (P = 0.021). At 6 months, the OR of at least 1 grade worsening of TR in the TV-ICD group as compared with the S-ICD group was 7.2 (95% CI: 3.3-15.8; P < 0.001). There were no differences between groups with respect to RV size or systolic function., Conclusions: Six months following TV-ICD insertion, there was a 7-fold increase in the risk of at least 1 grade worsening of TR, with 7% of individuals having TR that was moderate or severe. There was no detectable difference in RV size or function; however, longer follow-up is needed., Competing Interests: Funding Support and Author Disclosures This study was funded by Boston Scientific through an unrestricted research grant. Boston Scientific did not have any input into the preparation of this manuscript. Dr Leong has received consultancy fees from Boston Scientific. Dr Mondésert has received consultancy and speaking fees from Bostin Scientific, Abbott, Medtronic, and Biotronik. Dr Joza has received research support from Medtronic Inc; consulting fees from Boston Scientific; and honoraria from Biosense Webster Canada. Dr Healey has received research support and speaking fees from BMS/Pfizer, Boston Scientific, and Medtronic; speaking fees from Servier; and consultancy fees from Bayer and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Providers report needing higher sedative doses to achieve adequate sedation in patients with mental illnesses. These claims, however, have not been thoroughly assessed., Purpose: The purpose of the study was to measure the association between mental illness and the propofol dosage necessary to achieve a satisfactory level of anesthesia., Study Design, Setting, Sample: The study consisted of a single-center, retrospective cohort consisting of patients treated by oral and maxillofacial surgery at the University of Cincinnati Medical Center in 2020. The study was comprised of subjects 15 or older who were American Society of Anesthesiologists (ASA) classification I or II. Subjects under 15 or ASA III or higher were excluded from the study., Predictor Variable: The predictor variable was the presence or absence of mental illness., Main Outcome Variable(s): The primary outcome was the total dose of propofol, measured as the total amount of propofol administered divided by the patient's weight in kilograms divided by the length of the procedure in minutes (mg/kg/min). The secondary outcome was the Richmond Agitation-Sedation Scale (RASS) score achieved during sedation., Covariates: Sex, race, ethnicity, age, weight, body mass index, ASA score, prior tobacco use, marijuana use, use of adjunct midazolam, fentanyl, and ketamine during the procedure, and type of procedure served as covariates., Analyses: Test statistics were calculated using the Wilcoxon rank-sum test, Kruskal-Wallis test, Spearman rank correlation test, and χ 2 test for bivariate analyses. Linear and logistic regression models were used to estimate association while controlling for confounding. P values ≤ .05 were considered statistically significant., Results: The study sample was 409 subjects (36.92% male, mean age 28.27 ± 12.20 years). In bivariate analysis, mental illness did not show any association with propofol dose (mean dose with mental illness 150.85 ± 143.97 mg/kg/min, mean dose without mental illness 116.54 ± 104.16, P = .08) or RASS score (sufficiently sedated with mental illness 63.38%, sufficiently sedated without mental illness 58.80%, P = .36). After adjusting for all previously mentioned covariates, mental illness was statistically associated with propofol dose (P < .01). Adjusting for covariates, only sex had a statistically significant association with the RASS score (P < .05)., Conclusion and Relevance: The findings suggest that a patient's mental illness may influence the amount of sedative required to achieve satisfactory anesthesia., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: The advent of salt-based, high-nicotine electronic nicotine delivery systems [e-cigarettes] has contributed to their epidemic use among young people in the US, necessitating the need for policies to address the addictiveness of these products., Objective: To evaluate the effect of partial nicotine reduction on new-generation e-cigarette users' puffing behaviors., Design, Setting, and Participants: This randomized crossover clinical trial was conducted at the Clinical Research Lab for Tobacco Smoking at Florida International University in Miami between April 15, 2022, and October 17, 2023. Using a volunteering sampling method by distributing flyers and advertisements, current e-cigarette users (who preferred 5% nicotine concentration), aged 21 to 35 years, were included., Intervention: In a crossover design, participants completed 2 sessions of the same product (JUUL or NJOY) that differed by nicotine concentration (3% [JUUL] or 2.4% [NJOY] and 5% [JUUL or NJOY]) in random order. In each session, participants vaped up to 60 minutes ad libitum, preceded by 12 hours of nicotine abstinence., Main Outcomes and Measures: The primary outcomes were puffing topography parameters (eg, total session time, puffing time, total puffing number, interpuff interval, total inhaled volume, average puff volume, duration, and flow rate) measured during each session and plasma nicotine measured before and after each session., Results: Among 735 participants who were approached for eligibility, 675 were excluded, and 10 did not complete session 2. Of the 50 remaining current e-cigarette users (mean [SD] age, 23 [3] years; 56% men), 23 (46%) were low nicotine dependent. The median topography parameters were significantly higher during the e-cigarette use sessions with 3% or 2.4% nicotine concentration compared with 5% nicotine concentration for 3 outcomes: puffing time (1.3 minutes [IQR, 0.3-9.4 minutes] vs 1.2 minutes [IQR, 0.2-5.6 minutes]; P = .02), puff duration (2.6 seconds [IQR, 0.8-6.9 seconds] vs 2.4 seconds [IQR, 0.4-6.6 seconds]; P = .02), and total inhaled volume (1990.0 mL [IQR, 279.0-24 400.0 mL] vs 1490.0 mL [IQR, 148.0-14 300.0 mL]; P = .05). The median plasma nicotine boost observed in the 5% nicotine concentration condition (0.0060 mg/L [IQR, 0.0001-0.0249 mg/L]) was significantly higher than that in the 3% or 2.4% session (0.0043 mg/L [IQR, 0.0008-0.0225 mg/L]) (P = .001). Additionally, deeper puffing (increased average puff duration and average puff volume) was observed in participants with higher nicotine dependence (1.42 seconds [95% CI, 1.12-1.80 seconds]; P = .03) and male users (1.38 mL [95% CI, 1.09-1.75 mL]; P = .04) in response to nicotine reduction., Conclusions and Relevance: This randomized crossover clinical trial provides direct evidence that partial nicotine reduction in salt-based e-cigarettes was associated with acute compensatory puffing and the potential for increased exposure to toxicants. However, given the reduced nicotine delivery associated with nicotine reduction, the acute compensatory response observed in this study may not preclude a population benefit due to the marketing of less addictive products. These results suggest that at least for current e-cigarette users, partial nicotine reduction can lead to enhanced exposure to some toxicants in the short term., Trial Registration: ClinicalTrials.gov Identifier: NCT05205382.

Background: This study reports on the development of pictorial health warning labels for electronic nicotine delivery system (ENDS) using the Delphi approach with a panel of tobacco control experts. Twenty-four evidence-based ENDS-specific warnings corresponding to three themes (toxicity, health risks and specific harm) were developed and used in the Delphi study., Methods: We conducted a three-round online Delphi study among 60 experts (55% female) between June 2022 and April 2023. We balanced the panel in areas of expertise and positions relevant to ENDS (risks, benefits). In round 1, participants rated the warnings on attention, relevance to evidence and perceived effectiveness (harm perception, motivation to quit) and provided suggestions for improvement. In rounds 2 and 3, participants ranked the revised warnings based on importance in each theme. We assessed levels of agreement between participants using interquartile deviations and medians., Results: Warnings in theme 1, toxicity, received the highest ratings for perceived effectiveness on harm perception and encouraging quitting ENDS (p<0.05). Experts recommended using clear and affirmative text paired with emotion-provoking pictures and avoiding the rare side effects of ENDS. Most of the top-ranked warnings were from theme 3, ENDS-specific harm, pertained to lung damage, dual use of ENDS and cigarettes, nicotine addiction among youth, anti-ENDS industry sentiment and toxicity., Discussion: This study developed 24 evidence-based ENDS health warning labels using a systematic process that included several rounds of expert panel feedback. These warnings can be used to advance ENDS prevention and tobacco control policies and further target different populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

To improve the paper strength, a number of resins and polymeric materials are being used, which is not environmental friendly and sustainable. Therefore, bio-based paper additives for the papermaking industry are essential. In this investigation, a water soluble biopolymer like carboxymethyl chitosan (CMCh) was prepared. The degree of substitution of the prepared CMCh was 2.49. The solubility of the prepared CMCh was 2.0 (w/v) % at 50 °C, and the conductivity increased with the increase of CMCh concentration in water. The prepared CMCh was applied as dry and wet strength agent of unrefined and refined softwood pulps. Both pulp increased dry and wet strength with increasing CMCh dose. An addition of 2.0 % CMCh increased dry strength by 125 % and wet strength by 293 % of unrefined pulp. On the other hand, the dry and wet tensile index of refined pulp increased from 59.48 N·m/g to 66.11 N·m/g and 2.48 N·m/g to 3.47 N·m/g, respectively, with the addition of 1.0 % CMCh. The CMCh was also used in filler modification. The precipitated calcium carbonate (PCC) modified with CMCh increased the ash content in paper with improved strength properties. The CMCh can be used in papermaking both for improving paper strength and filler retention., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Cardiovascular disease, particularly acute coronary syndromes (ACS), is the leading cause of death in the United States. Minor fluctuations in hospital admissions for different conditions, including ACS, can be seen throughout the year. This study focuses on the impact of admission month on outcomes of acute coronary syndromes during the first year of the COVID-19 pandemic., Methods: This was a retrospective observational study of patients hospitalized with ACS from the National Inpatient Sample, during the years 2020 ( n  = 779,895) and 2019 ( n  = 935,975). We compared the monthly outcomes for every month to the outcomes for the month of January of that same year. The primary outcomes of interest were in-hospital mortality and time from admission to PCI., Results: Inpatient mortality for patients admitted with STEMI was significantly higher for admissions in the months of April, October and December of 2020 than January of that same year. For patients admitted with NSTEMI or UA, inpatient mortality was higher for admissions in April and December 2020 when compared to admissions in January 2020. Inpatient mortality for patients with STEMI, NSTEMI and UA was not different based on admission month in the year 2019., Conclusion: The month of admission significantly affected outcomes for patients admitted with ACS during the COVID-19 pandemic, with higher inpatient mortality and longer time from admission to PCI for certain months in 2020. Further studies should investigate disparities in monthly ACS outcomes for the year 2021 and onward, now that COVID-19 infections have been steadily declining.

The study was carried out to investigate the isolation of Escherichia coli from tracheal and oropharyngeal swab of clinically sick chickens. The antibiotic susceptibility patterns of the isolates to several antimicrobials were determined with a striking emphasis on oxytetracycline. The PCR technique was applied to detect tetA, tetB, and tetC in the tetracycline-resistant isolates. The isolates were initially screened for their resistance patterns against 6 antimicrobials of six different groups using the disc diffusion technique. The results showed that 41% tracheal, 51% oropharyngeal, and 34% samples from both sites were E. coli positive respectively. Antimicrobial resistance profiling of the isolates revealed that all the isolates were resistant to oxytetracycline and sulphamethoxazole-trimethoprim, and also 90 %, 82.9%, 63.4%, and 39% resistant to ciprofloxacin, amoxicillin, gentamicin, and colistin respectively. Notably, 82.9% isolates (95% CI 68.4%-91.8%) showed resistance to ≥3 groups of antimicrobials that means these were multi-drug resistant. Among the tetracycline-resistant isolates, 85.4% (95% CI 71.2%-93.5%), 29.3% (7.5%-44.6%), and 7.3% (1.8% - 20.1) were positive for tetA, tetB, and tetC genes respectively. The frequency of the isolation of E. coli is greater in oropharyngeal than tracheal and both kinds of samples. Commercial poultry with E . coli strains has acquired extensive resistance to oxytetracycline. This study suggests a possible association between the tetA gene and oxytetracycline resistance in E. coli isolates, but further investigations like knockdown, whole-genome sequencing, and rescue experiments are needed to establish a direct causal relationship., 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., (© 2023 The Authors.)

Background: Cryptosporidium spp. are responsible for significant diarrheal morbidity and mortality in under-5 children. There is no vaccine; thus, a focus on prevention is paramount. Prior studies suggest that person-to-person spread may be an important pathway for transmission to young children. Here we describe a longitudinal cohort study of 100 families with infants to determine rates of cryptosporidiosis within households during the coronavirus disease 2019 (COVID-19) pandemic., Methods: Families living in Mirpur, Bangladesh, with 1 infant aged 6-8 months were enrolled and followed with weekly illness survey and stool testing for Cryptosporidium for 8 months., Results: From December 2020 to August 2021, 100 families were enrolled. Forty-four percent of index children and 35% of siblings had at least 1 Cryptosporidium infection. Shedding of Cryptosporidium occurred for a mean (standard deviation) of 19 (8.3) days in index infants, 16.1 (11.6) days in children 1-5 years, and 16.2 (12.8) days in adults. A longer duration of Cryptosporidium shedding was associated with growth faltering in infants. There was a spike in Cryptosporidium cases in May 2021, which coincided with a spike in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases in the region., Conclusions: In this intensive, longitudinal study of Cryptosporidium infection in families we found high rates of cryptosporidiosis in infants and children, and prolonged parasite shedding, especially among malnourished children. These data support that transmission within the household is an important route of exposure for young infants and that treatment of nondiarrheal infection to interrupt person-to-person transmission within the home may be essential for preventing cryptosporidiosis in infants., Competing Interests: Potential conflicts of interest. M. A. reports grant-supported travel to the 2022 American Society of Tropical Medicine Hygiene conference (R01AI146123). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To remove the Ciprofloxacin (CIP) from aqueous solution, ZnO-Ag-Gp nanocomposite exhibited efficient photocatalytic properties. The biopersistent CIP is pervasive in surface water and also hazardous to human and animal health. This study utilized the hydrothermal technique to prepare Ag-doped ZnO hybridizing Graphite (Gp) sheet (ZnO-Ag-Gp) to degrade pharmaceuticals pollutant CIP from an aqueous medium. The structural and chemical compositions of the photocatalysts were determined by XRD, FTIR and XPS analysis. FESEM and TEM images revealed the nanorod ZnO with round shape Ag distributed on a Gp surface. The reduced bandgap of the ZnO-Ag-Gp sample enhanced the photocatalytic property which was measured by using UV-vis Spectroscopy. Dose optimization study found that 1.2 g/L is optimum for single (ZnO) and binary (ZnO-Gp and ZnO-Ag), where 0.3 g/L ternary (ZnO-Ag-Gp) exhibited maximum degradation efficiency (98%) within 60 min for 5 mg/L CIP. Pseudo 1st order reaction kinetics rate was found highest for ZnO-Ag-Gp (0.05983 min -1 ) and it decreased to 0.03428 min -1 for annealed sample. Removal efficiency decreased to only 90.97% at 5th run and hydroxyl radicals played a vital role to degrade CIP from aqueous solution. UV/ZnO-Ag-Gp will be a promising technique to degrade wide-ranging pharmaceutical antibiotics from the aquatic medium., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

The study aimed to estimate the dietary intake of vitamin A and its major food sources among rural pregnant women from the southwest region of Bangladesh. A multi-stage random cluster sampling method was used to select the respondents (N = 1012). A semi-structured questionnaire was used to collect the data, and statistical analysis was conducted using IBM SPSS 20.0. The mean age of the respondents was 23.27 ± 5.23 years, and the majority were in their second (48%) and third trimester (49%). The mean dietary intake of vitamin A was 392 ± 566 μg Retinol Activity Equivalent (RAE)/day (51% of Recommended Dietary Allowance). The contribution of β-carotene (plant source) and retinol (animal source) in vitamin A intake was about 60% and 40%, respectively. The major β-carotene contributing food groups were vegetables (dark and light) and tubers, and food items were colocasia, potato, beans, brinjal, and ripe tomatoes. On the other hand, the major retinol-contributing food groups were fish, eggs, and milk, and food items were small fish, Rui (carp) fish, and cow's milk. It was also observed that the consumption of food items from β-carotene and retinol-contributing food groups did not differ significantly among the three groups of respondents, but the variations in the amount of the different food items consumed were significant. Dietary vitamin A intake is low among pregnant women in the South-West region of Bangladesh. Hence, they are at a greater risk of adverse materno-fetal health outcomes associated with vitamin A deficiency., Competing Interests: The authors declare that there was no conflict of interest., (© 2023 The Authors.)

Background: In patients with ST-segment elevation myocardial infarction (STEMI), early initiation of high-intensity statin therapy, regardless of low-density lipoprotein (LDL) cholesterol levels, is the standard of practice worldwide.  Aims: We sought to determine the effect of a similar early initiation strategy, using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to the high-intensity statin, on LDL cholesterol in acute STEMI., Methods: In a randomised, double-blind trial we assigned 68 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) to early treatment with alirocumab 150 mg subcutaneously or to a matching sham control. The first injection was given before primary PCI regardless of the baseline LDL level, then at 2 and 4 weeks. The primary outcome was the percent reduction in direct LDL cholesterol up to 6 weeks, analysed using a linear mixed model.   Results: High-intensity statin use was 97% and 100% in the alirocumab and sham-control groups, respectively. At a median of 45 days, the primary outcome of LDL cholesterol decreased by 72.9% with alirocumab (2.97 mmol/L to 0.75 mmol/L) versus 48.1% with the sham control (2.87 mmol/L to 1.30 mmol/L), for a mean between-group difference of -22.3% (p<0.001). More patients achieved the European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guideline target of LDL ≤1.4 mmol/L in the alirocumab group (92.1% vs 56.7%; p<0.001). Within the first 24 hours, LDL declined slightly more rapidly in the alirocumab group than in the sham-control group (-0.01 mmol/L/hour; p=0.03) with similar between-group mean values.  Conclusions: In this randomised trial of routine early initiation of PCSK9 inhibitors in patients undergoing primary PCI for STEMI, alirocumab reduced LDL cholesterol by 22% compared with sham control on a background of high-intensity statin therapy. A large trial is needed to determine if this simplified approach followed by long-term therapy improves cardiovascular outcomes in patients with acute STEMI. (ClinicalTrials.gov: NCT03718286).

Background: Effects of probiotics on intestinal microbiota and feeding tolerance remain unclear in extremely low-birth-weight (ELBW) infants., Methods: ELBW infants were randomly assigned to receive probiotics or no intervention. Stool samples were collected prior to, 2 and 4 weeks after initiation, and 2 weeks after probiotics cessation for infants in the probiotics group, and at matched postnatal age time points for infants in the control group., Results: Of the 102 infants assessed for eligibility, sixty-two were included. Infants who received probiotics reached full enteral feeds sooner (Mean difference (MD) -1.8; 95% CI:-3.7 to -0.01 day), had a tendency toward lower incidence of hematochezia before hospital discharge (22.6% vs 3.2%; P = 0.053), and were less likely to require extensively hydrolyzed- or amino acids-based formulas to alleviate signs of cow's milk protein intolerance in the first 6 months of life (19.4% vs 51.6%; P = 0.008). Infants on probiotics were more likely to receive wide-spectrum antibiotics (64.5% vs 32.2%; P = 0.01). Multi-strain probiotics resulted in significant increase in fecal Bifidobacterium (P < 0.001) and Lactobacillus (P = 0.005), and marked reduction in fecal candida abundance (P = 0.04)., Conclusion: Probiotics sustained intestinal Bifidobacterium and reduced time to achieve full enteral feeds in extremely preterm infants. Probiotics might improve tolerance for cow's milk protein supplements., Clinical Trial Registration: This trial has been registered at www., Clinicaltrials: gov (identifier NCT03422562)., Impact: Probiotics may help extremely preterm infants achieve full enteral feeds sooner. Probiotics may improve tolerance for cow's milk protein supplements. Multi-strain probiotics can sustain intestinal Bifidobacterium and Lactobacillus until hospital discharge., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Second-hand smoke exposure from tobacco significantly contributes to morbidity and mortality worldwide. A cluster RCT in Bangladesh compared a community-based smoke-free home (SFH) intervention delivered in mosques, with or without indoor air quality (IAQ) feedback to households to no intervention. Neither was effective nor cost-effective compared to no intervention using an objective measure of second-hand smoke. This paper presents the process evaluation embedded within the trial and seeks to understand this., Methods: A mixed method process evaluation comprising interviews with 30 household leads and six imams (prayer leader in mosque), brief questionnaire completed by 900 household leads (75% response), fidelity assessment of intervention delivery in six (20%) mosques and research team records. Data were triangulated using meta-themes informed by three process evaluation functions: implementation, mechanisms of impact and context., Results: IMPLEMENTATION: Frequency of SFH intervention delivery was judged moderate to good. However there were mixed levels of intervention fidelity and poor reach. Linked Ayahs (verses of the Qur'an) with health messages targeting SHS attitudes were most often fully implemented and had greatest reach (along with those targeting social norms). Frequency and reach of the IAQ feedback were good., Mechanisms of Impact: Both interventions had good acceptability. However, views on usefulness of the interventions in creating a SFH were mixed. Individual drivers to behaviour change were new SFH knowledge with corresponding positive attitudes, social norms and intentions. Individual barriers were a lack of self-efficacy and plans., Context: Social context drivers to SFH intervention implementation in mosques were in place and important. No context barriers to implementation were reported. Social context drivers to SHS behaviour change were children's requests. Barriers were women's reluctance to ask men to smoke outside alongside general reluctance to request this of visitors. (Not) having somewhere to smoke outside was a physical context (barrier) and driver., Conclusions: Despite detailed development and adaption work with relevant stakeholders, the SFH intervention and IAQ feedback became educational interventions that were motivational but insufficient to overcome significant context barriers to reduce objectively measured SHS exposure in the home. Future interventions could usefully incorporate practical support for SFH behaviour change. Moreover, embedding these into community wide strategies that include practical cessation support and enforcement of SFH legislation is needed., Trial Registration: Current Controlled Trials ISRCTN49975452., (© 2022. The Author(s).)

Objectives: This umbrella review aims to summarise the evidence about electronic nicotine delivery systems' (ENDS) risk and safety health profile to inform ENDS health communication strategies., Data Sources and Study Selection: Six databases were searched for systematic reviews presenting evidence on ENDS-related health effects. Ninety reviews divided into five categories were included: toxicity=20, health effects=40, role in smoking cessation=24, role in transition to combustible cigarettes (CCs)=13 and industry marketing claims=4., Data Extraction: Findings were synthesised in narrative summaries. Meta-analyses were conducted by study type when appropriate. Quality assessment was conducted using the Measurement Tool to Assess Systematic Reviews. The Institute of Medicine's Levels of Evidence Framework was used to classify the evidence into high-level, moderate, limited-suggestive and limited-not-conclusive., Data Synthesis: We found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes serious injuries due to explosion or poisoning; increases smoking cessation in clinical trials but not in observational studies; increases CC initiation; and exposure to ENDS marketing increases its use/intention to use. Evidence was moderate for ENDS association with mental health and substance use, limited-suggestive for cardiovascular, and limited-not-conclusive for cancer, ear, ocular and oral diseases, and pregnancy outcomes., Conclusions: As evidence is accumulating, ENDS communication can focus on high-level evidence on ENDS association with toxicity, nicotine addiction, respiratory disease, ENDS-specific harm (explosion, poisoning) and anti-ENDS industry sentiment. Direct comparison between the harm of CCs and ENDS should be avoided., Prospero Registration Number: CRD42021241630., Competing Interests: Competing interests: All authors (except TE) certify that they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. TE is a paid consultant in litigation against the tobacco industry and also the electronic cigarette industry and is named on one patent for a device that measures the puffing behaviour of electronic cigarette users, on another patent application for a smartphone app that determines electronic cigarette device and liquid characteristics, and a third patent application for a smoking cessation intervention. The CSTP is supported by grant number U54DA036105 from the National Institute on Drug Abuse of the National Institutes of Health and the Center for Tobacco Products of the US Food and Drug Administration. The content of this paper is solely the responsibility of the authors and does not necessarily represent the views of the NIH or the FDA., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The National Nutrition Services of Bangladesh aims to deliver nutrition services through the primary health care system. Little is known about the feasibility of reshaping service delivery to close gaps in nutrition intervention coverage and utilization. We used a scenario-based feasibility testing approach to assess potential implementation improvements to strengthen service delivery. We conducted in-depth interviews with 31 service providers and 12 policymakers, and 5 focus group discussions with potential beneficiaries. We asked about the feasibility of four hypothetical scenarios for preventive and promotive nutrition service delivery: community-based events (CBE) for pregnant women, well-child services integrated into immunization contacts; CBE for well-children, and well-child visits at facilities. Opinions on service delivery platforms were mixed; some recommended new platforms, but others suggested strengthening existing delivery points. CBE for pregnant women was perceived as feasible, but workforce shortages emerged as a key barrier. Challenges such as equipment portability, upset children and a fast-moving service environment suggested low feasibility of integrating nutrition into outreach immunization contacts. In contrast, CBE and facility-based well-child visits emerged as feasible options, conditional on having the necessary workforce, structural readiness and budget support. On the demand side, enabling factors include using interpersonal communication and involving community leaders to increase awareness, organizing events at a convenient time and place for both providers and beneficiaries, and incentives for beneficiaries to encourage participation. In conclusion, integrating preventive and promotive nutrition services require addressing current challenges in the health system, including human resource and logistic gaps, and investing in creating demand for preventive services., (© 2022 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

A priori power and sample size calculations are crucial to appropriately test null hypotheses and obtain valid conclusions from all clinical studies. Statistical tests to evaluate hypotheses in microbiome studies need to consider intrinsic features of microbiome datasets that do not apply to classic sample size calculation. In this review, we summarize statistical approaches to calculate sample sizes for typical microbiome study scenarios, including those that hypothesize microbiome features to be the outcome, the exposure or the mediator, and provide relevant R scripts to conduct some of these calculations. This review is intended to be a resource to facilitate the conduct of sample size calculations that are based on testable hypotheses across several dimensions of the microbiome. Implementation of these methods will improve the quality of human or animal microbiome studies, enabling reliable conclusions that will generalize beyond the study sample., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

An elemental diet (ED) reduces adverse effects of chemotherapy, including oral mucositis, in patients with cancer. However, the detailed mechanism(s) of the healing effects of an ED remains unclear. In the present study, the protective effects of the ED, Elental ® , were examined against 5-fluorouracil (5-FU)-induced oral mucositis and salivary gland atrophy in mice. Mucositis was induced in female ICR mice by injection of 5-FU. The mice were orally administered Elental ® (ED group) or saline (control group). After treatment, the mice body weight, salivary gland weight and the histological changes in the salivary gland granular duct area were monitored. The mice body weight remained stable in the ED group, but was significantly decreased in the control group. Moreover, the salivary gland weight was higher in the ED group compared with the control group. In addition, the salivary gland granular duct area cells were larger in the ED group compared with the control group. Whole transcriptome analysis and network analysis were conducted to understand the mechanisms of action of Elental ® against oral mucositis. Whole transcriptome analysis and Ingenuity Pathways Analysis data suggested that Elental ® contributed to the recovery of mitochondrial function in 5-FU-damaged salivary glands. Immunohistochemical analysis of salivary gland tissue demonstrated that the expression of cytochrome c oxidase subunit 4 and epidermal growth factor were higher in the ED group compared with the control group. Next, the rate of apoptosis in the salivary glands was examined using terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The number of TUNEL-positive cells in the salivary glands was lower in the ED group compared with the control group. These findings suggested that Elental ® may protect mouse salivary glands from 5-FU-induced atrophic changes, which suggests that ED treatment may improve xerostomia and alleviate oral mucositis in patients with cancer receiving 5-FU-based chemotherapy., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Harada et al.)

Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Daily administration of the mixture accelerated the transition into a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Bifidobacterium-driven microbiome maturation was also linked to an anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains are ecosystem engineers that lead to an acceleration of microbiome maturation and immunological consequences in extremely premature infants., Competing Interests: Declaration of interests T.A.T. was the Research Director at Lallemand Health Solutions, the manufacturers of FloraBABY. The other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Exposure to secondhand smoke (SHS) is a health risk to non-smokers. Indoor particulate matter (PM 2.5 ) is associated with SHS exposure and is used as a proxy measure. However, PM 2.5 is non-specific and influenced by a number of environmental factors, which are subject to geographical variation. The nature of association between SHS exposure and indoor PM 2.5 -studied primarily in high-income countries (HICs) context-may not be globally applicable. We set out to explore this association in a low/middle-income country setting, Dhaka, Bangladesh., Methods: A cross-sectional study was conducted among households with at least one resident smoker. We inquired whether smoking was permitted inside the home (smoking-permitted homes, SPH) or not (smoke-free homes, SFH), and measured indoor PM 2.5 concentrations using a low-cost instrument (Dylos DC1700) for at least 22 hours. We describe and compare SPH and SFH and use multiple linear regression to evaluate which variables are associated with PM 2.5 level among all households., Results: We surveyed 1746 households between April and August 2018; 967 (55%) were SPH and 779 (45%) were SFH. The difference between PM 2.5 values for SFH (median 27 µg/m 3 , IQR 25) and SPH (median 32 µg/m 3 , IQR 31) was 5 µg/m 3 (p<0.001). Lead participant's education level, being a non-smoker, having outdoor space and smoke-free rule at home and not using kerosene oil for cooking were significantly associated with lower PM 2.5 ., Conclusions: We found a small but significant difference between PM 2.5 concentrations in SPH compared with SFH in Dhaka, Bangladesh-a value much lower than observed in HICs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the availability and success of live-attenuated oral vaccines, rotavirus (RV) remains the leading cause of pediatric gastroenteritis worldwide. Next-generation vaccines targeting RV VP8∗ are under evaluation, but the role of VP8∗-specific antibodies in human immunity to RV and their potential as immune correlates of protection remains underexplored., Methods: We measured plasma RV VP8∗-binding antibodies in 2 cohorts of young children in Dhaka, Bangladesh. Plasma from a cohort study of 137 unvaccinated children aged 6-24 months old hospitalized with acute gastroenteritis was assessed for VP8∗ antibody seropositivity. VP8∗ antibodies were compared with the current standard for RV immunity, total RV-specific IgA (RV-IgA). Additionally, VP8∗ antibody responses were measured as part of an immunogenicity trial of a monovalent, oral, live-attenuated RV vaccine (Rotarix)., Results: Fewer children with acute RV gastroenteritis were seropositive for VP8∗-binding IgA or IgG antibodies at hospital admission compared with RV-IgA, suggesting that the absence of VP8∗-binding antibodies more accurately predicts susceptibility to RV gastroenteritis than RV-IgA in unvaccinated children. However, when present, these antibodies appeared insufficient to protect fully from disease and no threshold antibody level for protection was apparent. In vaccinated children, these antibodies were very poorly induced by Rotarix vaccine, suggesting that VP8∗-specific antibodies alone are not necessary for clinical protection following oral vaccination., Conclusions: This work suggests that VP8∗-binding antibodies may not be sufficient or necessary for protection from RV gastroenteritis following prior RV infection or oral vaccination; the role of VP8∗ antibodies induced by parenteral vaccination with non-replicating vaccines remains to be determined., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Molecular diagnostic methods improve the detection of Shigella , yet their ability to detect Shigella drug resistance on direct stool specimens is less clear. We tested 673 stool specimens from a Shigella treatment study in Bangladesh, including 154 culture-positive stool specimens and their paired Shigella isolates. We utilized a TaqMan array card that included quantitative PCR (qPCR) assays for 24 enteropathogens and 36 antimicrobial resistance (AMR) genes. Shigella was detected by culture in 23% of stool specimens (154/673), while qPCR detected Shigella at diarrhea-associated quantities in 49% (329/673; P < 0.05). qPCR for AMR genes on the Shigella isolates yielded >94% sensitivity and specificity compared with the phenotypic susceptibility results for azithromycin and ampicillin. The performance for trimethoprim-sulfamethoxazole susceptibility was less robust, and the assessment of ciprofloxacin was limited because most isolates were resistant. The detection of AMR genes in direct stool specimens generally yielded low specificities for predicting the resistance of the paired isolate, whereas the sensitivity and negative predictive values for predicting susceptibility were often higher. For example, the detection of ermB or mphA in stool yielded a specificity of 56% but a sensitivity of 91% and a negative predictive value of 91% versus the paired isolate's azithromycin resistance result. Patients who received azithromycin prior to presentation were universally culture negative (0/112); however, qPCR still detected Shigella at diarrhea-associated quantities in 34/112 (30%). In sum, molecular diagnostics on direct stool specimens greatly increase the diagnostic yield for Shigella , including in the setting of prior antibiotics. The molecular detection of drug resistance genes in direct stool specimens had low specificity for confirming resistance but could potentially "rule out" macrolide resistance.

Introduction: Small intestine bacterial overgrowth (SIBO) is common in children from low-income countries and has been cross-sectionally associated with growth stunting. We sought to determine whether SIBO was associated with poor growth and neurodevelopmental in a longitudinal analysis., Methods: We measured SIBO by glucose hydrogen breath test (GHBT) at 18, 52, 78, and 104 weeks of life in a prospective longitudinal birth cohort of Bangladeshi children. Sociodemographic information and measures of enteric inflammation were analyzed as covariates. Diarrheal samples were tested for enteropathogens using polymerase chain reaction. Regression models were created using standardized mean GHBT area under the H2 curve (AUC) to determine associations with linear growth and cognitive, language, and motor scores on the Bayley-III Scales of Infant and Toddler Development at 2 years. We also investigated associations between GHBT AUC and enteropathogen exposure., Results: A 1-ppm increase in standardized mean GHBT AUC was associated with a 0.01-SD decrease in length-for-age Z score (P = 0.03) and a 0.11-point decrease in Bayley language score (P = 0.05) at 2 years of age in adjusted analysis. Enteroaggregative Escherichia coli, Enteropathogenic Escherichia coli, Giardia, and Enterocytozoon bieneusi were associated with increased GHBT AUC, whereas Clostridium difficile, norovirus GI, sapovirus, rotavirus, and Cryptosporidium were associated with decreased GHBT AUC. None were consistent across all 4 time points., Discussion: SIBO in the first 2 years of life is associated with growth stunting and decreased language ability in Bangladeshi infants and may represent a modifiable risk factor in poor growth and neurodevelopment in low-income countries., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background/aim: This study aimed to identify the most useful components of Elental ® in the treatment of 5-fluorouracil (FU)-induced mucositis and salivary gland atrophy in mice., Materials and Methods: Mice (except the control group) were intraperitoneally injected with 5-FU. The mice received saline (control group and 5-FU group), dextrin (Dextrin group), amino acids (17AA group), or Elental ® (Elental ® group)., Results: The volume and weight of salivary glands was higher in 17AA and Elental ® groups compared to 5-FU group. The number of mucous glands was higher, whereas the number of damaged granular ductal epithelial cells was lower in the salivary glands of all groups except the 5-FU group. Salivation was also decreased in the 5-FU group compared to the other groups., Conclusion: Amino acids could be the most effective components of Elental ® for protecting mouse salivary glands from 5-FU-induced atrophic changes, and might be useful in the treatment of oral mucositis in cancer patients., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: TAS-102 is effective against unresectable advanced or recurrent colorectal and gastric cancer. However, its effect on oral squamous cell carcinoma (OSCC) is still unknown. Here, we tried to clarify the possible effect of TAS-102 against angiogenesis and proliferation of human OSCC cells., Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, migration assay and mice xenograft models were used to determine the effect of TAS-102 on growth and migration of OSCC. The activity of phosphorylated nuclear factor kappa light-chain-enhancer of activated B-cells (NF-κB) (p-p65) in cells was detected by immunocytochemistry. The expression of p-AKT serine/threonine kinase 1 (p-AKT), p-p65, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF2) and CD31 in mouse tumors were detected by immunohistochemistry., Results: TAS-102 significantly inhibited growth and migration of OSCC both in vitro and in vivo. It suppressed the activity of NF-κB in cells. TAS-102 down-regulated the expression of p-AKT, VEGF, FGF2 and CD31, which was associated with reduced vascularization of HSC2 tumor lesions., Conclusion: These findings suggest that TAS-102 might inhibit angiogenesis and proliferation of OSCC cells., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The application of low-dimensional nanomaterials in clinical practice as efficient sensors has been increasing day by day due to progress in the field of nanoscience. In this research work, we have conducted a theoretical investigation to nominate a potential electrochemical sensor for the allopurinol (APN) drug molecule via studying the fundamental interactions of the drug molecule with two nanocages (carbon nanocage/CNC - C 24 and boron nitride nanocage/BNNC - B 12 N 12 ) and two nanosheets (graphene - C 54 H 18 and boron nitride - B 27 N 27 H 18 ) by means of the DFT B3LYP/6-31G(d,p) level of theory in both gas and water phases. The adsorption energies of APN-BNNC conjugated structures are in the range of -20.90 kcal mol -1 to -22.33 kcal mol -1 , which indicates that weak chemisorption has occurred. This type of interaction happened due to charge transfer from the APN molecule to BNNC, which was validated and characterized based on the quantum theory of atoms in molecules, natural bond analysis, and reduced density gradient analysis. The highest decreases in energy gap (36.22% in gas and 26.79% in water) and maximum dipole moment (10.48 Debye in gas and 13.88 Debye in water) were perceived for the APN-BNNC conjugated structure, which was also verified via frontier molecular orbital (FMO) and MEP analysis. Also, the highest sensitivity (BNNC > BNNS > CNC > GNS) and favorable short recovery time (in the millisecond range) of BNNC can make it an efficient detector for the APN drug molecule., 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., (This journal is © The Royal Society of Chemistry.)

Background: In health research, culturally and linguistically diverse (CALD) health care consumers are cited as hidden or hard to reach. This paper evaluates the approach used by researchers to attract and retain hard-to-reach CALD research participants for a study investigating health communication barriers between CALD health care users and health care professionals in regional Australia. As the study was taking place during the COVID-19 pandemic, subsequent restrictions emerged. Thus, recruitment and retention methods were adapted. This evaluation considered the effectiveness of recruitment and retention used throughout the pre-COVID and during-COVID periods., Objective: This evaluation sought to determine the effectiveness of recruitment and retention efforts of researchers during a study that targeted regional hard-to-reach CALD participants., Methods: Recruitment and retention methods were categorized into the following 5 phases: recruitment, preintervention data collection, intervention, postintervention data collection, and interviews. To compare the methods used by researchers, recruitment and retention rates were divided into pre-COVID and during-COVID periods. Thereafter, in-depth reflections of the methods employed within this study were made., Results: This paper provides results relating to participant recruitment and retainment over the course of 5 research phases that occurred before and during COVID. During the pre-COVID recruitment phase, 22 participants were recruited. Of these participants, 15 (68%) transitioned to the next phase and completed the initial data collection phase. By contrast, 18 participants completed the during-COVID recruitment phase, with 13 (72%) continuing to the next phase. The success rate of the intervention phase in the pre-COVID period was 93% (14/15), compared with 84.6% (11/13) in the during-COVID period. Lastly, 93% (13/14) of participants completed the postintervention data collection in the pre-COVID period, compared with 91% (10/11) in the during-COVID period. In total, 40 participants took part in the initial data collection phase, with 23 (58%) completing the 5 research phases. Owing to the small sample size, it was not determined if there was any statistical significance between the groups (pre- and during-COVID periods)., Conclusions: The success of this program in recruiting and maintaining regional hard-to-reach CALD populations was preserved over the pre- and during-COVID periods. The pandemic required researchers to adjust study methods, thereby inadvertently contributing to the recruitment and retention success of the project. The maintenance of participants during this period was due to flexibility offered by researchers through adaptive methods, such as the use of cultural gatekeepers, increased visibility of CALD researchers, and use of digital platforms. The major findings of this evaluation are 2-fold. First, increased diversity in the research sample required a high level of flexibility from researchers, meaning that such projects may be more resource intensive. Second, community organizations presented a valuable opportunity to connect with potential hard-to-reach research participants., (©Genevieve Perrins, Tabassum Ferdous, Dawn Hay, Bobby Harreveld, Kerry Reid-Searl. Originally published in JMIR Formative Research (https://formative.jmir.org), 02.11.2021.)

Exosomes are vesicles secreted by various kinds of cells, and they are rich in cholesterol, sphingomyelin (SM), phosphatidylcholine, and phosphatidylserine. Although cellular sphingolipid-mediated exosome release has been reported, the involvement of other lipid components of cell membranes in the regulation of exosome release is poorly understood. Here, we show that the level of exosome release into conditioned media is significantly reduced in cultured astrocytes prepared from apolipoprotein E (ApoE) knock-out mice when compared to those prepared from wild-type (WT) mice. The reduced level of exosome release was accompanied by elevated levels of cellular cholesterol. The addition of cholesterol to WT astrocytes significantly increased the cellular cholesterol levels and reduced exosome release. PI3K/Akt phosphorylation was enhanced in ApoE-deficient and cholesterol-treated WT astrocytes. In contrast, the depletion of cholesterol in ApoE-deficient astrocytes due to treatment with β-cyclodextrin recovered the exosome release level to a level similar to that in WT astrocytes. In addition, the reduced levels of exosome release due to the addition of cholesterol recovered to the control levels after treatment with a PI3K inhibitor (LY294002). The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway., 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 © 2021 Abdullah, Nakamura, Ferdous, Gao, Chen, Zou and Michikawa.)

Vascular endothelial growth factor (VEGF) serves an important role in new blood vessel formation or angiogenesis, which is a critical event in tumor growth and metastasis. Bevacizumab is a humanized monoclonal antibody against VEGF-A, whereas S-1 is a fluoropyrimidine antineoplastic agent that induces apoptosis in various types of cancer cells. The present study evaluated the antitumor effects of bevacizumab in combination with 5-fluorouracil (5-FU) or S-1 against oral squamous cell carcinoma (OSCC) in vitro and in vivo . Two human OSCC cell lines were used, namely the high VEGF-A-expressing HSC-2 cells and the low VEGF-A-expressing SAS cells. MTT assay was used to evaluate the effect of bevacizumab and/or 5-FU against HSC-2 and SAS cell proliferation. Additionally, the antitumor effect of bevacizumab was evaluated alone and in combination with S-1 against HSC-2 tumors in nude mice. S-1 (6.9 mg/kg/day) was administered orally every day for 3 weeks, and bevacizumab (5 ml/kg/day) was injected intraperitoneally twice per week for 3 weeks. Apoptotic cells in mouse tumors were detected using the TUNEL method, and cell proliferation and microvessel density (MVD) were determined by immunohistochemical staining of Ki-67 and CD31, respectively. Bevacizumab alone did not inhibit OSCC cell proliferation in vitro , and did not exhibit any synergistic inhibitory effect in combination with 5-FU in vitro . However, combined bevacizumab and S-1 therapy exerted synergistic and significant antitumor effects in vivo on HSC-2 tumor xenografts, and induced apoptosis in tumor cells. Furthermore, this combination therapy led to decreased MVD and cell proliferative abilities, as well as increased apoptosis in residual tumors. The present findings suggested that the bevacizumab plus S-1 combination therapy may exert antitumor effects in high VEGF-A-expressing OSCC cells., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Itashiki et al.)

In this investigation, the relationship between fiber properties and papermaking properties of 22 non-wood materials at the unrefined and refined states was assessed. The fiber length had positive and the cell wall thickness had negative correlation on the strength properties for the refined pulp. The relationship between papermaking properties with pulp quality, such as fines, curl index, kink index, external fibrillation, and coarseness, was also determined. The correlations of multiple regression equations of fiber quality parameters were 70.4% for the tensile index and 84.9% for the tear index for the refined pulp. The correlations of multiple regression equations of chemical characteristics of the samples were 81.9% for the pulp yield and 42.7% for the kappa number. Holocellulose and α-cellulose had a positive and lignin had a negative effect on the pulp yield., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Diarrheal pathogens have been associated with linear growth deficits. The effect of diarrheal pathogens on growth is likely due to inflammation, which also adversely affects neurodevelopment. We hypothesized that diarrheagenic pathogens would be negatively associated with both growth and neurodevelopment., Methods: We conducted a longitudinal birth cohort study of 250 children with diarrheal surveillance and measured pathogen burden in diarrheal samples using quantitative polymerase chain reaction. Pathogen attributable fraction estimates of diarrhea over the first 2 years of life, corrected for socioeconomic variables, were used to predict both growth and scores on the Bayley-III Scales of Infant and Toddler Development., Results: One hundred eighty children were analyzed for growth and 162 for neurodevelopmental outcomes. Rotavirus, Campylobacter, and Shigella were the leading causes of diarrhea in year 1 while Shigella, Campylobacter, and heat-stable toxin-producing enterotoxigenic Escherichia coli were the leading causes in year 2. Norovirus was the only pathogen associated with length-for-age z score at 24 months and was positively associated (regression coefficient [RC], 0.42 [95% confidence interval {CI}, .04 to .80]). Norovirus (RC, 2.46 [95% CI, .05 to 4.87]) was also positively associated with cognitive scores while sapovirus (RC, -2.64 [95% CI, -4.80 to -.48]) and typical enteropathogenic E. coli (RC, -4.14 [95% CI, -8.02 to -.27]) were inversely associated. No pathogens were associated with language or motor scores. Significant maternal, socioeconomic, and perinatal predictors were identified for both growth and neurodevelopment., Conclusions: Maternal, prenatal, and socioeconomic factors were common predictors of growth and neurodevelopment. Only a limited number of diarrheal pathogens were associated with these outcomes., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Local delivery of active agents using injectable or implantable hydrogels for tissue and bone regeneration is a promising therapy, but it remains challenging for controlling dose and duration of release. Simvastatin (SMV), a hydrophobic drug, has shown potential for osteogenic stimulation. Secure loading of hydrophobic drugs by physical interactions is particularly difficult to establish in hydrophilic polymer matrices, and their sustained release over several months for long-term regeneration has rarely been reported. Additionally, mechanical properties of hydrogels must be improved for a sufficient support while maintaining eventual biodegradability. This study assesses the effect of controlled SMV release from 3D-printed triple-network hydrogels for osteogenic stimulation and characterizes their mechanical and biological properties as an implant. SMV is loaded into polymeric micelles of polylactide/poly(ethylene glycol) triblock copolymers (PLA-PEG-PLA) and mixed with N-methacryloyl chitosan and PEG dimethacrylate to fabricate hydrogels by photo-cross-linked 3D printing. The hydrogel properties and drug release profiles have shown significant dependance on the polymer compositions. The SMV release from the triple-polymer-network hydrogel has continued for 17 weeks of observation. Cytocompatibility of hydrogels with various formulations is confirmed. The tunable triple-network hydrogels loaded with SMV provide a potential therapeutic value for bone regeneration., (© 2021 Wiley-VCH GmbH.)

Background: Azithromycin is frequently used to treat shigellosis; however, clinical outcomes are uncertain., Methods: We performed an observational cohort study in Bangladesh of patients with invasive diarrhea treated empirically with azithromycin. Susceptibility testing was performed by broth microdilution and disk diffusion post hoc on all Shigella isolates and clinical response was correlated with in vitro susceptibility., Results: There were 149 Shigella culture-positive patients in the primary analysis. Infection with Shigella with decreased susceptibility to azithromycin was significantly associated with persistence of diarrhea at day 5 (31% vs 12%; relative risk [RR], 2.66; 95% confidence interval [CI], 1.34-5.28), culture positivity at day 5 or 6 (35% vs 5%; RR, 5.26; 95% CI, 1.84-14.85), and a higher rate of overnight hospitalization (58% vs 39%; RR, 1.49; 95% CI, 1.06-2.09). Shigella flexneri was more common than Shigella sonnei (58% vs 36%); however, S. sonnei constituted most of the isolates with decreased susceptibility to azithromycin (67%) and most of the multidrug-resistant strains (54%); thus, poor clinical outcomes were associated with S. sonnei. The current epidemiological cutoff for S. flexneri of ≥16 µg/mL to define decreased susceptibility to azithromycin was clinically predictive of poor outcome. Patients with S. sonnei and a low MIC (4 µg/mL) still had elevated rates of persistent diarrhea and culture positivity., Conclusions: This study documents worse clinical outcomes for S. flexneri with decreased susceptibility to azithromycin, as well as S. sonnei, and supports the utility of susceptibility testing and clinical breakpoints for azithromycin. S. sonnei is an emerging drug-resistant threat., Clinical Trials Registration: NCT03778125., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE., Study Design: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition., Setting: Stakeholders from the United Kingdom., Subjects and Methods: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition., Results: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'., Conclusion: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life., Competing Interests: The authors have declared that no competing interests exist.

Background: Exposure to second-hand smoke from tobacco is a major contributor to global morbidity and mortality. We aimed to evaluate the efficacy and cost-effectiveness of a community-based smoke-free-home intervention, with or without indoor-air-quality feedback, in reducing second-hand-smoke exposure in homes in Bangladesh., Methods: We did a three-arm, cluster-randomised, controlled trial in Dhaka, Bangladesh, and randomly assigned (1:1:1) mosques and consenting households from their congregations to a smoke-free-home intervention plus indoor-air-quality feedback, smoke-free-home intervention only, or usual services. Households were eligible if they had at least one resident attending one of the participating mosques, at least one adult resident (age 18 years or older) who smoked cigarettes or other forms of smoked tobacco (eg, bidi, waterpipe) regularly (on at least 25 days per month), and at least one non-smoking resident of any age. The smoke-free-home intervention consisted of weekly health messages delivered within an Islamic discourse by religious leaders at mosques over 12 weeks. Indoor-air-quality feedback comprised providing households with feedback on their indoor air quality measured over 24 h. Households in the usual services group received no intervention. Masking of participants and mosque leaders was not possible. The primary outcome was the 24-h mean household airborne fine particulate matter (<2·5 microns in diameter [PM 2·5 ]) concentration (a marker of second-hand smoke) at 12 months after randomisation. Cost-effectiveness was estimated using incremental cost-effectiveness ratios (ICERs). This trial is registered with ISRCTN, 49975452., Findings: Between April 11 and Aug 2, 2018, we enrolled 1801 households from 45 mosques. 640 households (35·5%) were assigned to the smoke-free-home intervention plus indoor-air-quality feedback group, 560 (31·1%) to the smoke-free-home intervention only group, and 601 (33·4%) to the usual services group. At 12 months, the adjusted mean difference in household mean 24-h PM 2·5 concentration was -1·0 μg/m 3 (95% CI -12·8 to 10·9, p=0·88) for the smoke-free-home intervention plus indoor-air-quality feedback group versus the usual services group, 5·0 μg/m 3 (-7·9 to 18·0, p=0·45) for the smoke-free-home intervention only group versus the usual services group, and -6·0 μg/m 3 (-18·3 to 6·3, p=0·34) for the smoke-free-home intervention plus indoor-air-quality feedback group versus the smoke-free-home intervention only group. The ICER for the smoke-free-home intervention plus indoor-air-quality feedback versus usual services was US$653 per quality-adjusted life-year (QALY) gained, which was more than the upper limit of the Bangladesh willingness-to-pay threshold of $427 per QALY., Interpretation: The smoke-free-home intervention, with or without indoor-air-quality feedback, was neither effective nor cost-effective in reducing household second-hand-smoke exposure compared with usual services. These interventions are therefore not recommended for Bangladesh., Funding: Medical Research Council UK., Translation: For the Bengali translation of the abstract see Supplementary Materials section., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)