Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Elucidation of population stratifying markers and selective sweeps in crossbred Landlly pig population using genome-wide SNP data.

The present study was aimed at the identification of population stratifying markers from the commercial porcine SNP 60K array and elucidate the genome-wide selective sweeps in the crossbred Landlly pig population. Original genotyping data, generated on Landlly pigs, was merged in various combinations with global suid breeds that were grouped as exotic (global pig breeds excluding Indian and Chinese), Chinese (Chinese pig breeds only), and outgroup pig populations. Post quality control, the genome-wide SNPs were ranked for their stratifying power within each dataset in TRES (using three different criteria) and FIFS programs and top-ranked SNPs (0.5K, 1K, 2K, 3K, and 4K densities) were selected. PCA plots were used to assess the stratification power of low-density panels. Selective sweeps were elucidated in the Landlly population using intra- and inter-population haplotype statistics. Additionally, Tajima's D-statistics were calculated to determine the status of balancing selection in the Landlly population. PCA plots showed 0.5K marker density to effectively stratify Landlly from other pig populations. The A-score in DAPC program revealed the Delta statistic of marker selection to outperform other methods (informativeness and FST methods) and that 3000-marker density was suitable for stratification of Landlly animals from exotic pig populations. The results from selective sweep analysis revealed the Landlly population to be under selection for mammary (NAV2), reproductive efficiency (JMY, SERGEF, and MAP3K20), body conformation (FHIT, WNT2, ASRB, DMGDH, and BHMT), feed efficiency (CSRNP1 and ADRA1A), and immunity (U6, MYO3B, RBMS3, and FAM78B) traits. More than two methods suggested sweeps for immunity and feed efficiency traits, thus giving a strong indication for selection in this direction. The study is the first of its kind in Indian pig breeds with a comparison against global breeds. In conclusion, 500 markers were able to effectively stratify the breeds. Different traits under selective sweeps (natural or artificial selection) can be exploited for further improvement.

The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis.

BACKGROUND: Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear. METHODS: A systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined clinically as the relative risk of hospitalization/death during follow-up (≥14 days), and virologically as the SARS-CoV-2 viral clearance rate ratio (VCRR). The VCRR is the ratio of viral clearance rates between the intervention and control arms. The relationship between the clinical and virological treatment effects was assessed by mixed-effects meta-regression. RESULTS: From 57 potentially eligible RCTs, VCRRs were derived for 44 (52 384 participants); 32 had ≥1 clinical endpoint in each arm. Overall, 9.7% (R2) of the variation in clinical benefit was explained by variation in VCRRs with an estimated linear coefficient of -0.92 (95% CI: -1.99 to 0.13; P = 0.08). However, this estimate was highly sensitive to the inclusion of the recent very large PANORAMIC trial. Omitting this outlier, half the variation in clinical benefit (R2 = 50.4%) was explained by variation in VCRRs [slope -1.47 (95% CI -2.43 to -0.51); P = 0.003], i.e. higher VCRRs were associated with an increased clinical benefit. CONCLUSION: Methods of determining viral clearance in COVID-19 studies and the relationship to clinical outcomes vary greatly. As prohibitively large sample sizes are now required to show clinical treatment benefit in antiviral therapeutic assessments, viral clearance is a reasonable surrogate endpoint.

Understanding the association between intimate partner violence and sexually transmitted infections among women in India: a propensity score matching approach.

BACKGROUND: Intimate partner violence (IPV) against women can significantly impact their overall health. While numerous studies in developing nations highlight the association between IPV and sexually transmitted infections (STIs), the evidence available within the Indian context remains limited. Therefore, this study aims to fill this knowledge gap by investigating the relationship between exposure to different forms of IPV and the occurrence of STIs, using a quasi-experimental approach. METHODS: The study used a sample of 63 851 women aged 15-49 years from the latest National Family Health Survey-5. Propensity score matching (PSM) was employed to assess the 'treatment effect' from exposure to IPV (physical, emotional or sexual) in the past 12 months on STIs. RESULTS: About 12.2% of women (95% CI: 11.7% to 12.8%) reported symptoms of STIs at the time of the survey. Approximately 31.9% (95% CI: 31.2% to 32.7%) of women reported experiencing at least one form of IPV-either physical, emotional or sexual IPV. Of all forms of IPV, physical IPV was the most prevalent, reported by 28.6%, followed by emotional IPV (13.2%) and sexual IPV (5.7%). Women who experienced any form of IPV-whether physical, sexual or emotional-reported a higher prevalence of STIs (17.8%) as compared with those who did not experience any IPV (9.5%). The findings from the PSM analysis indicated that among the three forms of IPV, the impact of sexual IPV on STIs was the most pronounced. The average treatment effect on the treated from exposure to sexual IPV on STIs was 0.15 (95% CI 0.13 to 0.17). CONCLUSION: This study provides evidence of a significant association between IPV and STIs among women in India and underscores the urgent need for intensified efforts and interventions to address both IPV and STIs, to improve the overall health and well-being of women in India.

Wealth-based disparities in the prevalence of short birth interval in India: insights from NFHS-5.

BACKGROUND: Short birth interval (SBI) has profound implications for the health of both mothers and children, yet there remains a notable dearth of studies addressing wealth-based inequality in SBI and its associated factors in India. This study aims to address this gap by investigating wealth-based disparities in SBI and identifying the underlying factors associated with SBI in India. METHODS: We used information on 109,439 women of reproductive age (15-49 years) from the fifth round of the National Family Health Survey (2019-21). We assessed wealth-based inequality in SBI for India and its states using the Erreygers Normalised Concentration Index (ECI). Additionally, we used a multilevel binary logistic regression to assess the factors associated with SBI in India. RESULTS: In India, the prevalence of SBI was 47.8% [95% CI: 47.4, 48.3] during 2019-21, with significant variation across states. Bihar reported the highest prevalence of SBI at 61.2%, while Sikkim the lowest at 18.1%. SBI prevalence was higher among poorer mothers compared to richer ones (Richest: 33.8% vs. Poorest: 52.9%). This wealth-based inequality was visible in the ECI as well (ECI= -0.13, p < 0.001). However, ECI varied considerably across the states. Gujarat, Punjab, and Manipur exhibited the highest levels of wealth-based inequality (ECI= -0.28, p < 0.001), whereas Kerala showed minimal wealth-based inequality (ECI= -0.01, p = 0.643). Multilevel logistic regression analysis identified several factors associated with SBI. Mothers aged 15-24 (OR: 12.01, p < 0.001) and 25-34 (2.92, < 0.001) were more likely to experience SBI. Women who married after age 25 (3.17, < 0.001) and those belonging to Scheduled Caste (1.18, < 0.001), Scheduled Tribes (1.14, < 0.001), and Other Backward Classes (1.12, < 0.001) also had higher odds of SBI. Additionally, the odds of SBI were higher among mothers in the poorest (1.97, < 0.001), poorer (1.73, < 0.001), middle (1.62, < 0.001), and richer (1.39, < 0.001) quintiles compared to the richest quintile. Women whose last child had passed away were also significantly more likely to have SBI (2.35, < 0.001). Furthermore, mothers from communities with lower average schooling levels (1.18, < 0.001) were more likely to have SBI. Geographically, mothers from eastern (0.67, < 0.001) and northeastern (0.44, < 0.001) regions of India were less likely to have SBI. CONCLUSION: The significant wealth-based inequality in SBI in India highlights the need for targeted interventions focusing on economically disadvantaged women, particularly in states with high SBI prevalence. Special attention should be given to younger mothers and those from socially disadvantaged groups to enhance maternal and child health outcomes across the country.

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial.

In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. BACKGROUND: Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. METHODS: In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. RESULTS: In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. INTERPRETATION: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.

A district-level geospatial analysis of anaemia prevalence among rural men in India, 2019-21.

BACKGROUND: Despite its considerable impact on health and productivity, anemia among men has received limited attention. In a country as diverse as India, characterized by extensive geographic variations, there is a pressing need to investigate the nuanced spatial patterns of anemia prevalence among men. The identification of specific hotspots holds critical implications for policymaking, especially in rural areas, where a substantial portion of India's population resides. METHODS: The study conducted an analysis on a sample of 61,481 rural men from 707 districts of India, utilizing data from the National Family Health Survey-5 (2019-21). Various analytical techniques, including Moran's I, univariate LISA (Local Indicators of Spatial Association), bivariate LISA, and spatial regression models such as SLM (Spatial Lag Model), and SEM (Spatial Error Model) were employed to examine the geographic patterns and spatial correlates of anaemia prevalence in the study population. RESULTS: In rural India, three out of every ten men were found to be anemic. The univariate Moran's I value for anaemia was 0.66, indicating a substantial degree of spatial autocorrelation in anaemia prevalence across the districts in India. Cluster and outlier analysis identified five prominent 'hotspots' of anaemia prevalence across 97 districts, primarily concentrated in the eastern region (encompassing West Bengal, Jharkhand, and Odisha), the Dandakaranya region, the Madhya Pradesh-Maharashtra border, lower Assam, and select districts in Jammu and Kashmir. The results of SLM revealed significant positive association between anaemia prevalence at the district-level and several key factors including a higher proportion of Scheduled Tribes, men in the 49-54 years age group, men with limited or no formal education, individuals of the Muslim faith, economically disadvantaged men, and those who reported alcohol consumption. CONCLUSIONS: Substantial spatial heterogeneity in anaemia prevalence among men in rural India suggests the need for region-specific targeted interventions to reduce the burden of anaemia among men in rural India and enhance the overall health of this population.

Lower Airway Dysbiosis Augments Lung Inflammatory Injury in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke is a causative factor; however, not all heavy smokers develop COPD. Microbial colonization and infections are contributing factors to disease progression in advanced stages. Objectives: We investigated whether lower airway dysbiosis occurs in mild-to-moderate COPD and analyzed possible mechanistic contributions to COPD pathogenesis. Methods: We recruited 57 patients with a >10 pack-year smoking history: 26 had physiological evidence of COPD, and 31 had normal lung function (smoker control subjects). Bronchoscopy sampled the upper airways, lower airways, and environmental background. Samples were analyzed by 16S rRNA gene sequencing, whole genome, RNA metatranscriptome, and host RNA transcriptome. A preclinical mouse model was used to evaluate the contributions of cigarette smoke and dysbiosis on lower airway inflammatory injury. Measurements and Main Results: Compared with smoker control subjects, microbiome analyses showed that the lower airways of subjects with COPD were enriched with common oral commensals. The lower airway host transcriptomics demonstrated differences in markers of inflammation and tumorigenesis, such as upregulation of IL-17, IL-6, ERK/MAPK, PI3K, MUC1, and MUC4 in mild-to-moderate COPD. Finally, in a preclinical murine model exposed to cigarette smoke, lower airway dysbiosis with common oral commensals augments the inflammatory injury, revealing transcriptomic signatures similar to those observed in human subjects with COPD. Conclusions: Lower airway dysbiosis in the setting of smoke exposure contributes to inflammatory injury early in COPD. Targeting the lower airway microbiome in combination with smoking cessation may be of potential therapeutic relevance.

Development of Rapid and Affordable Virus-Mimicking Artificial Positive Controls.

A major bottleneck in the development of detection assays is the availability of positive controls. Their acquisition can be problematic, their maintenance is expensive, and without them, assays cannot be validated. Herein, we present a novel strategy for the development of virus-mimicking artificial positive controls (ViMAPCs). The time between design and application is less than 5 days, unlike alternatives which normally take several weeks to obtain and implement. The ViMAPCs provide a realistic representation of natural infection unlike alternatives and allow for an effortless recognition of laboratory-based contamination. The feasibility and adaptability of the strategy was evaluated using several RNA and DNA plant viruses. ViMAPCs can be used in diagnostics laboratories but also in the monitoring of pathogen outbreaks where rapid response is of utmost importance.

More than Mycobacterium tuberculosis: site-of-disease microbial communities, and their functional and clinical profiles in tuberculous lymphadenitis.

BACKGROUND: Lymphadenitis is the most common extrapulmonary tuberculosis (EPTB) manifestation. The microbiome is important to human health but uninvestigated in EPTB. We profiled the site-of-disease lymph node microbiome in tuberculosis lymphadenitis (TBL). METHODS: Fine-needle aspiration biopsies were collected from 158 pretreatment presumptive TBL patients in Cape Town, South Africa. 16S Illumina MiSeq rRNA gene sequencing was done. RESULTS: We analysed 89 definite TBLs (dTBLs) and 61 non-TBLs (nTBLs), which had similar α- but different ß-diversities (p=0.001). Clustering identified five lymphotypes prior to TB status stratification: Mycobacterium-dominant, Prevotella-dominant and Streptococcus-dominant lymphotypes were more frequent in dTBLs whereas a Corynebacterium-dominant lymphotype and a fifth lymphotype (no dominant taxon) were more frequent in nTBLs. When restricted to dTBLs, clustering identified a Mycobacterium-dominant lymphotype with low α-diversity and non-Mycobacterium-dominated lymphotypes (termed Prevotella-Corynebacterium, Prevotella-Streptococcus). The Mycobacterium dTBL lymphotype was associated with HIV-positivity and features characteristic of severe lymphadenitis (eg, larger nodes). dTBL microbial communities were enriched with potentially proinflammatory microbial short-chain fatty acid metabolic pathways (propanoate, butanoate) vs nTBLs. 11% (7/61) of nTBLs had Mycobacterium reads BLAST-confirmed as Mycobacterium tuberculosis complex. CONCLUSIONS: TBL at the site-of-disease is not microbially homogeneous. Distinct microbial community clusters exist that, in our setting, are associated with different clinical characteristics, and immunomodulatory potentials. Non-Mycobacterium-dominated dTBL lymphotypes, which contain taxa potentially targeted by TB treatment, were associated with milder, potentially earlier stage disease. These investigations lay foundations for studying the microbiome's role in lymphatic TB. The long-term clinical significance of these lymphotypes requires prospective validation.

Spatiotemporal change in socioeconomic inequality in hygienic menstrual product use among adolescent girls in India during 2015-2019.

BACKGROUND: The use of hygienic products, such as sanitary napkins, tampons, and menstrual cups, to absorb menstrual blood is vital for the health and well-being of adolescent girls in India. However, the degree of inequity in the use of such products among this subpopulation remains inadequately explored. To fill this critical knowledge gap, this study aims to investigate the spatiotemporal dynamics of hygienic product use among adolescent girls in India from 2015 to 2020. METHODS: In this cross-sectional study, we analyzed data from 117,749 to 114,839 adolescent girls aged 15-19, obtained from two consecutive rounds of the National Family Health Survey (NFHS) conducted in India during 2015-16 and 2019-21. Our approach involved utilizing Erreygers' Concentration Index (ECI) and Concentration Curve to quantitatively assess and visually represent socioeconomic inequality in hygienic product usage. Additionally, we investigated the spatiotemporal variation in this inequality over the study period and decomposed the ECI to identify the key contributing factors. RESULTS: The findings reveal that hygienic product usage among adolescent girls in India has increased by 13 percentage points (PP), from 37% in 2015-16 to 50% in 2019-21. This increase is also visible across all household wealth quintiles. However, the bottom quintiles experienced a greater rise (+ 15 to 16 PP) than the top quintile (+ 8 PP). During the study period, the ECI reduced marginally, from 0.48 in 2015-16 to 0.43 in 2019-21. However, the extent of this reduction varied across different states. The greatest reduction in ECI was recorded in Punjab (-0.23 points), Telangana (-0.16 points), and West Bengal (-0.14 points). In contrast, there were a number of states with high socioeconomic inequality (ECI > 0.30) in 2015-16, where inequality reduction was minimal (< 0.05 points) over the study period. This included more developed states of Kerala, Karnataka, Maharashtra and Gujarat and relatively less developed states of Odisha, Jharkhand, Chhattisgarh, Uttar Pradesh, and Assam. Some states, such as Bihar and Madhya Pradesh, recorded an increase in socioeconomic inequality over the study period, with ECI rising to 0.31 and 0.46 (highest in the country) in 2019-21. The decomposition analysis revealed that the inequality in using hygienic products was primarily explained by place of residence, exposure to mass-media, education, and region of residence. CONCLUSIONS: The findings suggest the need for targeted policies to reduce existing socioeconomic inequality in the usage of hygienic products among adolescent girls in India. Specifically, interventions should target regions with low use of hygienic products, economically disadvantaged groups, and poor and vulnerable populations. State-specific policies and programs are also necessary to address the disparities in socioeconomic inequality. Additionally, efforts to reduce inequality should address the underlying factors contributing to inequality.

Transfluthrin is Associated with High Susceptibility to Asthma in Children with Promoter Variants of Beta Chain of High-Affinity Receptor IgE and Tumour Necrosis Factors-α Genes.

This study investigates the genetic variations in FcεR1ß-109 C/T (rs512555) and TNF-α-308 G/A (rs1800629) genes and examines whether the mosquito repellent transfluthrin (TFT) modifies the risk for asthmatic children. A case-control study was conducted involving 130 asthmatic children and 123 age-sex matched controls. Differential leukocyte counts, IgE, and hs-CRP levels were estimated using a five-part haematology analyzer and Beckman Coulter (AU480), respectively. Genetic variations in FcεR1ß-109 and TNF-α-308 were analysed using restriction fragment length polymorphism. Serum TFT levels were measured using gas chromatography-tandem mass spectrometry. Asthmatic children had significantly increased total leukocyte, neutrophil, lymphocyte, eosinophil, and basophil counts (p < 0.0001), while their monocyte counts were lower compared to controls (p < 0.0001). TFT levels were higher in asthmatic children (1.38 ± 0.91 vs. control 0.69 ± 0.41µg/L, p < 0.0001), which predominantly induced wheezing. Elevated TFT levels were associated with an increased risk of childhood asthma (OR: 3.08, p < 0.0001). Children with the FcεRIß TT (OR: 2.39, p < 0.017) and TNF-α GG genotypes (OR: 7.17, p < 0.0001) were more susceptible to asthma. TFT synergistically enhanced the risk of asthma in both FcεRIß-109 TT (OR: 5.3, p = 0.001) and TNF-α-308 GG (OR: 17.18, p < 0.0001) genotypes. TFT levels were correlated with IgE (r = 0.363; p = 0.006), hs-CRP (r = 0.324; p = 0.049) and eosinophil (r = 0.300; p = 0.038), respectively. IgE and eosinophils were correlated (r = 0.599, p = 0.001) in the FcεRIß TT genotype-carrying asthmatic children. Similarly, neutrophils and hs-CRP were correlated (r = 0.768, p < 0.0001) in asthmatic children with TNF-α GG genotype. The risk of asthma is inherently higher in children with FcεRIß TT and TNF-α GG variants. TFT exposure amplifies the risk of asthma in children among all the subgenotypes of both genes. TFT influences IgE and eosinophil in FcεRIß TT genotype while it influences neutrophils and hs-CRP in TNF-α GG genotypes.

Short birth interval and associated factors in rural India: A cross-sectional study.

Short Birth Interval (SBI) is one of the main causes of adverse maternal and child health outcomes. A 33-month birth-to-birth interval between two successive live births should be followed to minimize the risk of adverse maternal and child health. This study aimed to examine the prevalence of SBI and the associated factors in rural India. Information on 98,522 rural mothers from the fourth round of National Family Health Survey data was analyzed. Bivariate statistics, logistic regression, Moran's I, and Cluster and Outlier Analysis have been used to assess the prevalence and spatial pattern of SBI in rural India. Results revealed that about half of the mothers in rural India had experienced SBI. Rural Indian mothers whose child was not alive (OR = 1.76, 95% CI = 1.63-1.90), were not using any contraceptive methods (OR = 1.42, 95 % CI = 1.37-1.48) and not breastfeeding (OR = 2.73, 95% CI = 2.50-2.97) were more likely to experience SBI. On the other hand, rural mothers from the middle, richer and richest wealth quintiles (OR = 0.91, 95% CI = 0.86-0.97; OR = 0.84, 95% CI = 0.80-0.92; OR = 0.60, 95% CI = 0.55-0.66) and of age over 30 years (OR = 0.38., 95% CI = 0.36-0.39) were less likely to experience SBI. Analysis of spatial patterns revealed clear east-west differences in the prevalence of SBI. There was strong clustering of high values of SBI in most districts across the central, northern, western, and southern regions. The study suggests the need to introduce appropriate interventions and programs focused on reducing the prevalence of SBI in rural India.

Inhibitory Effects of Loganin on Adipogenesis In Vitro and In Vivo.

Obesity is characterized by the excessive accumulation of mature adipocytes that store surplus energy in the form of lipids. In this study, we investigated the inhibitory effects of loganin on adipogenesis in mouse preadipocyte 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) in vitro and in mice with ovariectomy (OVX)- and high-fat diet (HFD)-induced obesity in vivo. For an in vitro study, loganin was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs, lipid droplets were evaluated by oil red O staining, and adipogenesis-related factors were assessed by qRT-PCR. For in vivo studies, mouse models of OVX- and HFD-induced obesity were orally administered with loganin, body weight was measured, and hepatic steatosis and development of excessive fat were evaluated by histological analysis. Loganin treatment reduced adipocyte differentiation by accumulating lipid droplets through the downregulation of adipogenesis-related factors, including peroxisome proliferator-activated receptor γ (Pparg), CCAAT/enhancer-binding protein α (Cebpa), perilipin 2 (Plin2), fatty acid synthase (Fasn), and sterol regulatory element binding transcription protein 1 (Srebp1). Loganin administration prevented weight gain in mouse models of obesity induced by OVX and HFD. Further, loganin inhibited metabolic abnormalities, such as hepatic steatosis and adipocyte enlargement, and increased the serum levels of leptin and insulin in both OVX- and HFD-induced obesity models. These results suggest that loganin is a potential candidate for preventing and treating obesity.

Effect of Different Chemical Solvents on Bond Strength of Orthodontic Brackets: An In Vitro Study.

AIM: The purpose of the present study was to evaluate the impact of various chemical solvents on bond strength of orthodontic brackets. MATERIALS AND METHODS: One hundred healthy human premolars with undamaged buccal surfaces that were extracted for orthodontic purposes were gathered. Using 37% orthophosphoric acid, primer, and Transbond XT adhesive, ceramic 0.018" × 0.022" slot orthodontic brackets were adhered to the tooth surface. Following thermocycling, all samples were divided into four groups, with 25 samples in each group: group I: control; group II: application of ethanol; group III: application of acetone; and group IV: application of dimethyl sulfoxide (DMSO). Following the debonding tests, a double-ocular stereomicroscope was used to inspect the tooth surfaces. Additionally, adhesive remnant index (ARI) values were evaluated at 40× magnification. Data were recorded and statistically analyzed. RESULTS: The bond strength was lesser in acetone applied group (16.18 ± 3.64) followed by DMSO applied group (22.08 ± 2.86), ethanol applied group (24.36 ± 4.02), and control group (27.14 ± 3.68). There was a highly significant difference found between the chemical solvents group. The ARI score 3 was present in control (12%), ethanol (8%), and DMSO (4%), and it was absent in acetone applied group. The ARI score 0 was more in acetone applied group (24%). CONCLUSION: The present study concluded that the reduced debonding force was found with the application of acetone solvent followed by DMSO, ethanol, and control groups. Applying acetone can be a substitute technique to help with ceramic bracket debonding. CLINICAL SIGNIFICANCE: Orthodontic bracket debonding cannot occur without shear bond strength (SBS). The need for an ideal debonding technique for ceramic brackets without negative consequences arises from the risk of enamel damage that frequently follows the process. Acetone treatment prior to ceramic bracket debonding could be an alternate clinical technique to preventing enamel damage and facilitating debonding. How to cite this article: Bhushan R, Singh S, Sam G, et al. Effect of Different Chemical Solvents on Bond Strength of Orthodontic Brackets: An In Vitro Study. J Contemp Dent Pract 2023;24(12):940-943.

Dynamic Changes in Circulatory Cytokines and Chemokines Levels in Mild to Severe COVID-19 Patients.

Immune dysregulation is a key feature of the coronavirus disease-2019 (COVID-19). However, disparities in responses across ethnic groups are underappreciated. This study aimed to determine the relationship between chemokines and cytokines and the severity of COVID-19. Multiplex magnetic bead-based Luminex-100 was used to assess chemokine and cytokine levels in COVID-19 patients at admission (day-1) and after 4 days. The mean age of the patients recruited was 54.3 years, with 19 (63.3%) males. COVID-19 patients had significantly lower lymphocyte, monocyte, hemoglobin and eosinophil levels than controls (p < 0.05). COVID-19 patients showed significantly higher neutrophil levels than controls (p < 0.05). The baseline levels of IL-2, IL-6, IL-8, IL-10, and IFN-α/γ significantly increased in COVID-19 patients (p < 0.05). Chemokine levels (IP-10, MCP-1, MIG, and CCL-5) were significantly in COVID-19 patients. IL-8, IP-10, and MIG levels were significantly higher in the patients with severe COVID-19 (p < 0.05). Individuals with mild COVID-19 showed significantly higher levels of INF-α, IL-2, IL-6, and IL-8, whereas IL-10 levels were significantly lower (p < 0.05). TNF-levels decreased significantly in individuals with severe COVID-19, whereas IL-6, IL-8, and MIG levels increased (p < 0.05). After 4 days, INFα-, IL-2, IL-6, IL-8, IP-10, and MIG levels were significantly higher in patients with mild disease, whereas IL-6, MIG, and TNF-αlevels were significantly higher in patients with severe disease (p < 0.05). Thus, we conclude that COVID-19 is characterized by INF-α/γ, IL-6, IL-10, IP-10, MCP-1, MIG, and CCL5 dysregulation. IL-8, MIG, and IP-10 levels distinguish between moderate and severe COVID-19. Changes in INF-α, IL-2, IL-6, IL-8, IP-10, and MIG levels can be used to monitor disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01108-x.

A non-canonical promoter element drives spurious transcription of horizontally acquired bacterial genes.

RNA polymerases initiate transcription at DNA sequences called promoters. In bacteria, the best conserved promoter feature is the AT-rich -10 element; a sequence essential for DNA unwinding. Further elements, and gene regulatory proteins, are needed to recruit RNA polymerase to the -10 sequence. Hence, -10 elements cannot function in isolation. Many horizontally acquired genes also have a high AT-content. Consequently, sequences that resemble the -10 element occur frequently. As a result, foreign genes are predisposed to spurious transcription. However, it is not clear how RNA polymerase initially recognizes such sequences. Here, we identify a non-canonical promoter element that plays a key role. The sequence, itself a short AT-tract, resides 5 base pairs upstream of otherwise cryptic -10 elements. The AT-tract alters DNA conformation and enhances contacts between the DNA backbone and RNA polymerase.

Menstrual hygiene practices among adolescent women in rural India: a cross-sectional study.

BACKGROUND: Exclusive use of hygienic methods (sanitary napkins, locally prepared napkins, tampons, and menstrual cups) to prevent the visibility of bloodstains during menstruation is still considerably low among adolescent women in rural India. However, no prior research has explored the prevalence and determinants of exclusive hygienic methods among rural Indian adolescent women. To address this gap, this study examines the factors affecting adolescent women's exclusive use of hygienic methods in rural India. Additionally, this study explores state- and district-level geographical disparities in the exclusive use of hygienic methods among adolescent women in rural India. METHODS: Information on 95,551 adolescent women from rural India from the latest round of National Family Health Survey (NFHS-5) was analyzed. Bivariate statistics and multilevel logistic regression analysis were used to assess the Individual- and community-level factors associated with exclusive use of hygienic methods among adolescent women in rural India. Choropleth maps were used to discern the geographical disparities in the exclusive use of hygienic methods. RESULTS: In rural India, only 42% of adolescent women exclusively used hygienic methods, with substantial geographic disparities at the state and district levels. At the state level, the exclusive use of hygienic methods varied from 23% in Uttar Pradesh to 85% in Tamil Nadu. Even greater variation was observed at the district level. There was a clear north-south divide in the exclusive use of hygienic methods among adolescent women in rural India. The results of multilevel logistic regression indicated a considerable amount of variation in the exclusive use of hygienic methods at community level which further reduced when controlled for individual and community-level factors. Rural Indian adolescent women with higher education (AOR:3.20, 95% CI: 2.81-3.64), from general category (AOR: 1.14, 95% CI: 1.07-1.21), with medium mass media exposure (AOR: 1.43, 95% CI: 1.35-1.51), and from richest wealth quintile (AOR: 3.98, 95% CI: 3.69-4.30) were more likely to use hygienic methods exclusively. CONCLUSION: Wide differential across biodemographic and socioeconomic groups, and substantial geographic disparities at state- and district-level in the exclusive use of hygienic methods suggests a need to adopt context-specific interventions for adolescent women in rural India. Distribution of subsidized or free menstrual hygiene methods to disadvantaged adolescent women, and in the low-prevalence districts may increase the level of exclusive use of hygienic methods remarkably.

Widespread suppression of intragenic transcription initiation by H-NS.

Widespread intragenic transcription initiation has been observed in many species. Here we show that the Escherichia coli ehxCABD operon contains numerous intragenic promoters in both sense and antisense orientations. Transcription from these promoters is silenced by the histone-like nucleoid structuring (H-NS) protein. On a genome-wide scale, we show that 46% of H-NS-suppressed transcripts in E. coli are intragenic in origin. Furthermore, many intergenic promoters repressed by H-NS are for noncoding RNAs (ncRNAs). Thus, a major overlooked function of H-NS is to prevent transcription of spurious RNA. Our data provide a molecular description for the toxicity of horizontally acquired DNA and explain how this is counteracted by H-NS.

Effects of Loganin on Bone Formation and Resorption In Vitro and In Vivo.

Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast-osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.