Early childhood neurodevelopmental milestones in children with allergic diseases: the Japan Environment and Children's Study (JECS).

This study investigated the potential link between early childhood allergic diseases and neurodevelopmental milestone attainment during the first 3 years of life. Utilizing data from a large-scale prospective birth cohort study in Japan, encompassing 87,986 children, we examined physician-diagnosed and caregiver-reported allergic conditions, including atopic dermatitis (AD), asthma, and food allergy (FA). Neurodevelopmental milestones were assessed using the Ages and Stages Questionnaires at 1, 1.5, 2, 2.5, and 3 years of age. Stabilized inverse probability-weighted generalized estimating equation models were employed to estimate odds ratios (ORs). Our analysis revealed no significant association of AD and asthma with delay in communication, gross motor, fine motor, problem-solving, and personal-social skills during the initial 3 years of life. However, children with FA showed an increased likelihood of experiencing gross motor delay compared with that shown by those without FA (weighted adjusted OR: 1.14). Despite this, no significant association of FA with other developmental domains was observed. Early childhood allergies may not influence neurodevelopmental delays. However, there is a potential association between FA and delays, specifically in gross motor skills, that warrants routine developmental monitoring and additional investigations.

Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero.

Importance: Corticosteroids and ß2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero exposure to these medications remain unclear. Objective: To investigate the association between timing of in utero exposure to corticosteroids and ß2-adrenergic agonists and offspring neurodevelopmental milestones during the first 3 years of life. Design, Setting, and Participants: This cohort study obtained data from the Japan Environment and Children's Study, an ongoing birth cohort study conducted in collaboration with 15 Regional Centers across Japan. Participants were mother-offspring pairs who were recruited between January 1, 2011, and March 31, 2014. Data were analyzed between January and February 2023. Exposure: Corticosteroids and ß2-adrenergic agonists were the exposure of interest. Timing of corticosteroid and ß2-adrenergic agonist exposure included early pregnancy (weeks 0-12), mid- to late pregnancy (weeks >12), and both stages of pregnancy. Main Outcomes and Measures: Offspring neurodevelopmental milestones (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition, at 6, 12, 18, 24, 30, and 36 months. Results: In total, 91 460 mother-offspring pairs were analyzed. Among mothers, the mean (SD) age at delivery was 31.20 (5.05) years. Among offspring, 46 596 (50.9%) were males and 44 864 (49.1%) were females, of whom 66.4% had a gestational age of 39 to 41 weeks. During early, mid- to late, and both stages of pregnancy, 401 (0.4%), 935 (1.0%), and 568 (0.6%) offspring, respectively, were exposed to corticosteroids, whereas 170 (0.2%), 394 (0.4%), and 184 (0.2%), respectively, were exposed to ß2-adrenergic agonists. No association of corticosteroid exposure during early, mid- to late, and both stages of pregnancy with all 5 neurodevelopmental milestones was found. Similarly, no association between ß2-adrenergic agonist use during early pregnancy and all 5 neurodevelopmental milestones was observed. An association was found between ß2-adrenergic agonist exposure during mid- to late pregnancy and delayed personal-social skills (adjusted odds ratio, 1.48; 95% CI, 1.01-2.32; P = .045). Conclusions and Relevance: Results of this study found no association between in utero corticosteroid and ß2-adrenergic agonist exposure and offspring neurodevelopmental outcomes, regardless of the timing of exposure. Despite the limitations and low power of the study, the findings suggest that corticosteroids and ß2-adrenergic agonists are safe for pregnant individuals with asthma and the neurodevelopment of their offspring.

Increased knowledge levels of patients with diabetes in resource-limited communities after receiving peer-led education.

Diabetes self-management education through peer support has been beneficial, especially in regions with limited medical resources. Studying the effects of education offered by trained peers of patients will facilitate tailoring the peer-led education programs to the regions' specific needs. Here, we evaluated changes in diabetes-related indicators in Filipino patients who received a peer-led education. We used data on 23 patients (age, 67.83 ± 6.69 years; 82.6% female) who participated in all five surveys performed every 6 months from March 2017 to March 2019. After the second survey until the end of this study, the participants were educated in diabetes self-management by their 13 peers who previously had received the training in diabetes self-management. Participants' knowledge of diabetes and the related 'cause, risk factors, nature of diabetes and complications' subindicator were greater on all surveys after starting the peer-led education compared with those on the second survey (i.e. before starting the education); these values did not differ between the first two surveys. Because increasing patients' knowledge can enhance their ability to self-manage their disease and thus improve their quality of life, strategies to expand patients' knowledge about diabetes should be included when organizing peer-led education in regions with limited medical resources.

Cognitive and Emotional Changes in Peer Educators of Type 2 Diabetes Patients After Starting Peer-Support Activities.

Background: Diabetes self-management education through peer support has beneficial effects, especially in regions with limited medical resources. To ensure peer educators continue to provide peer-led education programs, it is important that they remain motivated to instruct patients. Here, to explore measures to enhance peer-educators' motivation toward such programs, we examined the cognitive and emotional changes in Filipino type 2 diabetics after 7-month activities as peer educators. Methods: We individually performed semi-structured interviews with 13 peer educators with 20 years of age or above in August 2017 (immediately before starting their peer-education activities) and in March 2018 (7 months after the start). The first interview was performed after the peer educators had received 2-day training of diabetes self-management. In both interviews, we asked the peer educators about their feelings toward peer-led educational activities (e.g., satisfaction, difficulty, reward, confidence, and challenges). Their replies about their own cognition and emotions were interpreted and integrated, and then analyzed qualitatively. Results: Four and seven categories were extracted from the first and second interviews, respectively. The category "Cognition of patients' active learning attitudes and of positive changes in patients' physical conditions and behavior" observed in the second interview led to "Cognition of growth as a peer educator" and "Satisfaction with supporting patients as a peer educator." These two feelings gave the peer educators' "Increased motivation to continue the activities as a peer educator." This motivation was also associated with "Active collaboration among peer educators," which was affected by "Difficulties and concerns in working as a peer educator." Conclusion: To sustain diabetic peer-led education programs, we suggest that interventions be implemented that increase peer educators' motivation toward their activities and stimulate their awareness of the importance of collaborating with one another. Such collaboration should help to overcome the difficulties they may face in providing peer-led education.

Volatile compounds of Bacillus pseudomycoides induce growth and drought tolerance in wheat (Triticum aestivum L.).

The plant growth-boosting biofilm-forming bacteria Bacillus pseudomycoides is able to promote growth and drought stress tolerance in wheat by suppressing the MYB gene, which synthesizes Myb protein (TaMpc1-D4) through secreted volatile compounds. In the present study, Triticum aestivum seeds were inoculated with five distinct bacterial strains. The growth, germination rate, root-shoot length, RWC, and chlorophyll content of seedlings were investigated. Furthermore, the levels of soluble sugars, proteins, H2O2, NO, cell death, and antioxidant enzymes (CAT, SOD, POD, and APX) were observed throughout the growth stage. All of the results showed that B. pseudomycoides had a substantially higher ability to form biofilm and promote these traits than the other strains. In terms of molecular gene expression, B. pseudomycoides inoculation strongly expressed the Dreb1 gene by silencing the expression of MYB gene through secreted volatile compounds. For identifying the specific volatile compound that silenced the MYB gene, molecular docking with Myb protein was performed. Out of 45 volatile compounds found, 2,6-ditert-butylcyclohexa-2,5-diene-1,4-dione and 3,5-ditert-butylphenol had a binding free energy of - 6.2 and - 6.5, Kcal/mol, respectively, which predicted that these compounds could suppress this protein's expression. In molecular dynamics simulations, the RMSD, SASA, Rg, RMSF, and hydrogen bonding values found assured the docked complexes' binding stability. These findings suggest that these targeted compounds may be suppressing Myb protein expression as well as the expression of Dreb1 and other drought response genes in wheat. More research (field trial) into plant growth and drought stress is needed to support the findings of this study.

Plant-derived compounds effectively inhibit the main protease of SARS-CoV-2: An in silico approach.

The current coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus 2 (SARS-CoV-2), involves severe acute respiratory syndrome and poses unprecedented challenges to global health. Structure-based drug design techniques have been developed targeting the main protease of the SARS-CoV-2, responsible for viral replication and transcription, to rapidly identify effective inhibitors and therapeutic targets. Herein, we constructed a phytochemical dataset of 1154 compounds using deep literature mining and explored their potential to bind with and inhibit the main protease of SARS-CoV-2. The three most effective phytochemicals Cosmosiine, Pelargonidin-3-O-glucoside, and Cleomiscosin A had binding energies of -8.4, -8.4, and -8.2 kcal/mol, respectively, in the docking analysis. These molecules could bind to Gln189, Glu166, Cys145, His41, and Met165 residues on the active site of the targeted protein, leading to specific inhibition. The pharmacological characteristics and toxicity of these compounds, examined using absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses, revealed no carcinogenicity or toxicity. Furthermore, the complexes were simulated with molecular dynamics for 100 ns to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen profiles from the simulation trajectories. Our analysis validated the rigidity of the docked protein-ligand. Taken together, our computational study findings might help develop potential drugs to combat the main protease of the SARS-CoV-2 and help alleviate the severity of the pandemic.

Short- and Long-Term Effects of Drought on Selected Causes of Mortality in Northern Bangladesh.

Drought has exacerbated morbidity and mortality worldwide. Here, a time series study was conducted in northern Bangladesh to evaluate the impact of drought on selected causes of mortality during 2007-2017. Rainfall and temperature data from six meteorological stations were used to analyze drought and non-drought periods and to categorize mild, moderate, severe, and extreme drought based on the 3-month and 12-month Standardized Precipitation Index (SPI) and Standardized Precipitation Evaporation Index (SPEI). A generalized linear model with Poisson regression with log link, a negative binomial with log link, and a zero-inflated Poisson model were used to determine associations between drought severity and mortality. The SPI and SPEI produced slightly different analysis results. Compared with the SPEI, the SPI showed a stronger and more sensitive correlation with mortality. The relative risk for respiratory disease mortality was high, and Saidpur was the most vulnerable area. Health care expenditure was negatively associated with mortality. High temperatures during the drought period were associated with suicide-related mortality in Rajshahi. The impact of drought on mortality differed with small changes in climate. The findings of this study improve our understanding of the differences between the two most used drought indicators and the impact of drought on mortality.

Phytomedicines to Target Hepatitis B Virus DNA Replication: Current Limitations and Future Approaches.

Hepatitis B virus infection (HBV) is one of the most common causes of hepatitis, and may lead to cirrhosis or hepatocellular carcinoma. According to the World Health Organization (WHO), approximately 296 million people worldwide are carriers of the hepatitis B virus. Various nucleos(t)ide analogs, which specifically suppress viral replication, are the main treatment agents for HBV infection. However, the development of drug-resistant HBV strains due to viral genomic mutations in genes encoding the polymerase protein is a major obstacle to HBV treatment. In addition, adverse effects can occur in patients treated with nucleos(t)ide analogs. Thus, alternative anti-HBV drugs of plant origin are being investigated as they exhibit excellent safety profiles and have few or no side effects. In this study, phytomedicines/phytochemicals exerting significant inhibitory effects on HBV by interfering with its replication were reviewed based on different compound groups. In addition, the chemical structures of these compounds were developed. This will facilitate their commercial synthesis and further investigation of the molecular mechanisms underlying their effects. The limitations of compounds previously screened for their anti-HBV effect, as well as future approaches to anti-HBV research, have also been discussed.

Dermal Papilla Cell-Derived Extracellular Vesicles Increase Hair Inductive Gene Expression in Adipose Stem Cells via ß-Catenin Activation.

Recently, extracellular vesicle (EV)-mediated cell differentiation has gained attention in developmental biology due to genetic exchange between donor cells and recipient cells via transfer of mRNA and miRNA. EVs, also known as exosomes, play a role in maintaining paracrine cell communication and can induce cell proliferation and differentiation. However, it remains unclear whether adipose-derived stem cells (ASCs) can adopt dermal papilla (DP)-like properties with dermal papilla cell-derived extracellular vesicles (DPC-EVs). To understand the effect of DPC-EVs on cell differentiation, DPC-EVs were characterized and incubated with ASCs, of monolayer and spheroid cell cultures, in combination with the CAO1/2FP medium specialized for dermal papilla cells (DPCs). DPC-like properties in ASCs were initially evaluated by comparing several genes and proteins with those of DPCs via real-time PCR analysis and immunostaining, respectively. We also evaluated the presence of hair growth-related microRNAs (miRNAs), specifically mir-214-5P, mir-218-5p, and mir-195-5P. Here, we found that miRNA expression patterns varied in DPC-EVs from passage 4 (P4) or P5. In addition, DPC-EVs in combination with CAP1/2FP accelerated ASC proliferation at low concentrations and propagated hair inductive gene expression for versican (vcan), alpha-smooth muscle actin (α-sma), osteopontin (opn), and N-Cam (ncam). Comparison between the expression of hair inductive genes (vcan, α-sma, ctnb, and others), the protein VCAN, α-SMA and ß-Catenin (CTNB), and hair inductive miRNAs (mir-214-5P, mir-218-5p, and mir-195-5p) of DPC-EVs revealed similarities between P4 DPC-EVs-treated ASCs and DPCs. We concluded that early passage DPC-EVs, in combination with CAP1/2FP, enabled ASCs to transdifferentiate into DPC-like cells.

The Influence of Atopic Dermatitis on Health-Related Quality of Life in Bangladesh.

Atopic dermatitis (AD) is the foremost non-fatal skin-related disease that affects all age groups. Despite the growing prevalence of AD in low- and middle-income countries, its physiological consequences remain overlooked in countries like Bangladesh. Therefore, we aim to assess and characterize the influence of AD on the health-related quality of life (HRQoL) in Bangladeshi patients. A cross-sectional study comprising 184 eligible adults (83 men and 101 women; mean age, 33.46 ± 15.44 years) was conducted at the dermatology outpatient department of Shaheed Suhrawardy Medical College Hospital (a tertiary hospital in Dhaka, Bangladesh). AD was determined using the UK Working Party criteria. A structured questionnaire, Eczema Area and Severity Index (EASI), and Dermatology Life Quality Index (DLQI) were administered to obtain information on patient characteristics, AD severity, and HRQoL. The mean DLQI score for the entire sample was 11.29 ± 5.27 (range, 1-26), and 51.60% reported the disease greatly affected their lives. Bivariate analysis revealed significant differences in self-rated health measures of DLQI scores in terms of self-reported AD severity, overall health, and the EASI. In multivariable regression models adjusted for patient characteristics, the self-perceived severe AD group reported significantly higher DLQI scores (coefficient = 2.72; 95% confidence interval (CI) = 0.38-5.05; p = 0.022) than the mild group. Concurrently, we observed a substantial increase in the DLQI scores among patients with moderate and severe EASI scores (coefficient = 1.96, 95% CI = 0.08-3.92, p < 0.05 and coefficient = 4.35, 95% CI = 1.98-6.72, p < 0.001, respectively) than in those with mild EASI scores, suggesting that HRQoL was markedly influenced by greater AD severity. These findings highlight the need for a more patient-centric approach to the management of AD in order to alleviate patient suffering and, thereby, improve HRQoL.