DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

Altered Mental Status: An Important but Overlooked Presenting Symptom of COVID-19 in Older Adults.

OBJECTIVES: To determine whether altered mental status (AMS) as a presenting symptom in older adults with COVID-19 is independently associated with adverse outcomes. METHODS: A retrospective single center observational study of admitted patients (n = 421) age greater than 60 and a positive COVID-19 test. Outcomes included mortality, intubation, acute respiratory distress syndrome, acute kidney injury, and acute cardiac injury. Multivariate regression analysis was used to determine if presenting with AMS was associated with adverse outcomes. RESULTS: There was an increased risk of mortality (RR 1.29, 95% CI 1.05-1.57), intubation (RR 1.52, 95% CI 1.09-2.12) and AKI (RR 1.42, 95% CI 1.13-1.78) in patients that presented with AMS. CONCLUSIONS: During a global pandemic, prognostic indicators are vital to help guide the clinical course of patients, reduce healthcare cost, and preserve life. Our study suggests that AMS can play a major role in diagnostic algorithms in older adults with COVID-19.

Non-invasive positive pressure ventilation versus endotracheal intubation in treatment of COVID-19 patients requiring ventilatory support.

IMPORTANCE: Initial guidelines recommended prompt endotracheal intubation rather than non-invasive ventilation (NIV) for COVID-19 patients requiring ventilator support. There is insufficient data comparing the impact of intubation versus NIV on patient-centered outcomes of these patients. OBJECTIVE: To compare all-cause 30-day mortality for hospitalized COVID-19 patients with respiratory failure who underwent intubation first, intubation after NIV, or NIV only. DESIGN: Retrospective study of patients admitted in March and April of 2020. SETTING: A teaching hospital in Brooklyn, New York City. PARTICIPANTS: Adult COVID-19 confirmed patients who required ventilator support (non-invasive ventilation and/or endotracheal intubation) at discretion of treating physician, were included. EXPOSURES: Patients were categorized into three exposure groups: intubation-first, intubation after NIV, or NIV-only. PRIMARY OUTCOME: 30-day all-cause mortality, a predetermined outcome measured by multivariable logistic regression. Data are presented with medians and interquartile ranges, or percentages with 95% confidence intervals, for continuous and categorical variables, respectively. Covariates for the model were age, sex, qSOFA score ≥ 2, presenting oxygen saturation, vasopressor use, and greater than three comorbidities. A secondary multivariable model compared mortality of all patients that received NIV (intubation after NIV and NIV-only) with the intubation-first group. RESULTS: A total of 222 were enrolled. Overall mortality was 77.5% (95%CI, 72-83%). Mortality for intubation-first group was 82% (95%CI, 73-89%; 75/91), for Intubation after NIV was 84% (95%CI, 70-92%; 37/44), and for NIV-only was 69% (95%CI, 59-78%; 60/87). In multivariable analysis, NIV-only was associated with decreased all-cause mortality (odds ratio [OR]: 0.30, 95%CI, 0.13-0.69). No difference in mortality was observed between intubation-first and intubation after NIV. Secondary analysis found all patients who received NIV to have lower mortality than patients who were intubated only (OR: 0.44, 95%CI, 0.21-0.95). CONCLUSIONS & RELEVANCE: Utilization of NIV as the initial intervention in COVID-19 patients requiring ventilatory support is associated with significant survival benefit. For patients intubated after NIV, the mortality rate is not worse than those who undergo intubation as their initial intervention.

The impact of obesity on COVID-19 complications: a retrospective cohort study.

BACKGROUND: Obesity is an epidemic in New York City, the global epicenter of the coronavirus pandemic. Previous studies suggest that obesity is a possible risk factor for adverse outcomes in COVID-19. OBJECTIVE: To elucidate the association between obesity and COVID-19 outcomes. DESIGN: Retrospective cohort study of COVID-19 hospitalized patients tested between March 10 and April 13, 2020. SETTING: SUNY Downstate Health Sciences University, a COVID-only hospital in New York. PARTICIPANTS: In total, 684 patients were tested for COVID-19 and 504 were analyzed. Patients were categorized into three groups by BMI: normal (BMI 18.50-24.99), overweight (BMI 25.00-29.99), and obese (BMI ≥ 30.00). MEASUREMENTS: Primary outcome was 30-day in-hospital mortality, and secondary outcomes were intubation, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute cardiac injury (ACI). RESULTS: There were 139 patients (27%) with normal BMI, 150 patients who were overweight (30%), and 215 patients with obesity (43%). After controlling for age, gender, diabetes, hypertension, and qSOFA score, there was a significantly increased risk of mortality in the overweight (RR 1.4, 95% CI 1.1-1.9) and obese groups (RR 1.3, 95% CI 1.0-1.7) compared with those with normal BMI. Similarly, there was a significantly increased relative risk for intubation in the overweight (RR 2.0, 95% CI 1.2-3.3) and obese groups (RR 2.4, 95% CI 1.5-4.0) compared with those with normal BMI. Obesity did not affect rates of AKI, ACI, or ARDS. Furthermore, obesity appears to significantly increase the risk of mortality in males (RR 1.4, 95% CI 1.0-2.0, P = 0.03), but not in females (RR 1.2, 95% CI 0.77-1.9, P = 0.40). CONCLUSION: This study reveals that patients with overweight and obesity who have COVID-19 are at increased risk for mortality and intubation compared to those with normal BMI. These findings support the hypothesis that obesity is a risk factor for COVID-19 complications and should be a consideration in management of COVID-19.

Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro.

BACKGROUND: Cerebral malaria (CM) is associated with morbidity and mortality despite the use of potent anti-malarial agents. Brain endothelial cell activation and dysfunction from oxidative and inflammatory host responses and products released by Plasmodium falciparum-infected erythrocytes (IE), are likely the major contributors to the encephalopathy, seizures, and brain swelling that are associated with CM. The development of adjunctive therapy to reduce the pathological consequences of host response pathways could improve outcomes. A potentially protective role of the nuclear factor E2-related factor 2 (NRF2) pathway, which serves as a therapeutic target in brain microvascular diseases and central nervous system (CNS) inflammatory diseases such as multiple sclerosis was tested to protect endothelial cells in an in vitro culture system subjected to tumour necrosis factor (TNF) or infected red blood cell exposure. NRF2 is a transcription factor that mediates anti-oxidant and anti-inflammatory responses. METHODS: To accurately reflect clinically relevant parasite biology a unique panel of parasite isolates derived from patients with stringently defined CM was developed. The effect of TNF and these parasite lines on primary human brain microvascular endothelial cell (HBMVEC) activation in an in vitro co-culture model was tested. HBMVEC activation was measured by cellular release of IL6 and nuclear translocation of NFκB. The transcriptional and functional effects of dimethyl fumarate (DMF), an FDA approved drug which induces the NRF2 pathway, on host and parasite induced HBMVEC activation was characterized. In addition, the effect of DMF on parasite binding to TNF stimulated HBMVEC in a semi-static binding assay was examined. RESULTS: Transcriptional profiling demonstrates that DMF upregulates the NRF2-Mediated Oxidative Stress Response, ErbB4 Signaling Pathway, Peroxisome Proliferator-activated Receptor (PPAR) Signaling and downregulates iNOS Signaling and the Neuroinflammation Signaling Pathway on TNF activated HBMVEC. The parasite lines derived from eight paediatric CM patients demonstrated increased binding to TNF activated HBMVEC and varied in their binding and activation of HBMVEC. Overall DMF reduced both TNF and CM derived parasite activation of HBMVEC. CONCLUSIONS: These findings provide evidence that targeting the NRF2 pathway in TNF and parasite activated HBMVEC mediates multiple protective pathways and may represent a novel adjunctive therapy to improve infection outcomes in CM.

Assessment of radon transportation and uranium content in the tectonically active zone of Himalaya, India.

The study shows how geology and tectonic activity affect the soil gas 222Rn concentration. The tectonically active zone, namely the Ghuttu region, which is located within the Himalayan seismic belt, was studied to decipher its impact on soil gas 222Rn concentrations. A soil gas 222Rn study was performed in the soil at a depth of 30 cm, and it varied from 426 ± 156 Bq m-3 to 24,057 ± 1110 Bq m-3 with an average of 5356.5 ± 1634.6 Bq m-3, and at 60 cm below the soil surface, the concentration varied from 1130 ± 416 Bq m-3 to 30,236 ± 1350 Bq m-3 with an average of 8928.5 ± 2039.5 Bq m-3. These concentrations vary in soil from -3.4 % to 437.3 % as the depth moves from 30 cm to 60 cm. The variation in uranium content also shows anomalies, and higher values of uranium content in the soil affect the radon concentration in the study area. The average soil gas 222Rn concentration in the Ghuttu window was found to be higher than that in its surrounding region. This is likely due to transportation from daughter products of uranium. 222Rn mass exhalation rate measurements were also carried out, and a weak correlation with the soil gas 222Rn concentration was observed. A significant variation in the mass exhalation rate was noticed in tectonically active areas. This study is vital to understanding the behavior of radon and uranium in tectonic regions.

Microalgae as next generation plant growth additives: Functions, applications, challenges and circular bioeconomy based solutions.

Sustainable agriculture practices involve the application of environment-friendly plant growth promoters and additives that do not negatively impact the health of the ecosystem. Stringent regulatory frameworks restricting the use of synthetic agrochemicals and the increase in demand for organically grown crops have paved the way for the development of novel bio-based plant growth promoters. In this context, microalgae biomass and derived agrochemicals offer novel sources of plant growth promotors that enhance crop productivity and impart disease resistance. These beneficial effects could be attributed to the presence of wide range of biomolecules such as soluble amino acid (AA), micronutrients, polysaccharides, phytohormones and other signaling molecules in microalgae biomass. In addition, their phototrophic nature, high photosynthetic efficiency, and wide environmental adaptability make them an attractive source of biostimulants, biofertilizers and biopesticides. The present review aims to describe the various plant growth promoting metabolites produced by microalgae and their effects on plant growth and productivity. Further, the effects elicited by microalgae biostimulants with respect to different modes of applications such as seed treatments, foliar spray and soil/root drenching is reviewed in detail. In addition, the ability of microalgae metabolites to impart tolerance against various abiotic and biotic stressors along with the mechanism of action is discussed in this paper. Although the use of microalgae based biofertilizers and biostimulants is gaining popularity, the high nutrient and water requirements and energy intensive downstream processes makes microalgae based technology commercially unsustainable. Addressing this challenge, we propose a circular economy model of microalgae mediated bioremediation coupled with biorefinery approaches of generating high value metabolites along with biofertilizer applications. We discuss and review new trends in enhancing the sustainability of microalgae biomass production by co-cultivation of algae with hydroponics and utilization of agriculture effluents.

Assessing the health risks associated with the usage of water-atomization shower systems in buildings.

In the context of climate change policies, buildings must implement solutions to reduce energy and water consumption. One such solution is showering with water atomization showerheads, which can significantly reduce water and energy usage. However, the lack of risk assessment for users' health has hindered the widespread adoption of this technology. To address this gap, we assess the risk of spreading bacteria, in particular the pathogenic bacterium Legionella pneumophila, from shower hose biofilms of different ages grown under controlled or uncontrolled conditions considering different levels of water hardness, during showering using water atomization showerheads (ECO) or continuous flow showerheads (STA). We compared the aerosol and bioaerosol emission - total, viable and cultivable - during a 10 min shower event between the two shower systems. We showed that the water-atomization showerhead emitted slightly more nanoparticles smaller than 0.45 µm and slightly fewer particles larger than 0.5 µm than the continuous flow showerhead. Additionally, ECO showerheads emitted fewer cultivable bacteria than STA, regardless of the biofilm's age or growth conditions. When Legionella pneumophila was detected in biofilms, ECO showerheads released slightly less cultivable Legionella in the first flush of shower water compared to the STA, ranging from 6.0 × 102 to 1.6 × 104 CFU·L-1. However, cultivable L. pneumophila was not detected in the aerosols emitted during showering with either showerhead. These findings suggest that emerging water-drop emission technologies might affect human exposure to aerosols differently than traditional systems, emphasizing the importance of assessing the health risks associated with any new shower system. Additionally, these findings provide valuable insights for achieving a balance between water and energy conservation.

Mitochondrial nanomotion measured by optical microscopy.

Nanometric scale size oscillations seem to be a fundamental feature of all living organisms on Earth. Their detection usually requires complex and very sensitive devices. However, some recent studies demonstrated that very simple optical microscopes and dedicated image processing software can also fulfill this task. This novel technique, termed as optical nanomotion detection (ONMD), was recently successfully used on yeast cells to conduct rapid antifungal sensitivity tests. In this study, we demonstrate that the ONMD method can monitor motile sub-cellular organelles, such as mitochondria. Here, mitochondrial isolates (from HEK 293 T and Jurkat cells) undergo predictable motility when viewed by ONMD and triggered by mitochondrial toxins, citric acid intermediates, and dietary and bacterial fermentation products (short-chain fatty acids) at various doses and durations. The technique has superior advantages compared to classical methods since it is rapid, possesses a single organelle sensitivity, and is label- and attachment-free.

Microalgae as a sustainable source of edible proteins and bioactive peptides - Current trends and future prospects.

The global demand for protein ingredients is continuously increasing owing to the growing population, rising incomes, increased urbanization, and aging population. Conventionally, animal-derived products (dairy, egg, and meat) satisfy the major dietary protein requirements of humans. With the global population set to reach 9.6 billion by 2050, there would be a huge deficit in meeting dietary protein requirements. Therefore, it is necessary to identify sustainable alternative protein sources that could complement high-quality animal proteins. In recent years, microalgae have been advocated as a potential industrial source of edible proteins owing to their wide and excellent ecological adaptation. Microalgae can grow in marginal areas utilizing non-potable wastewaters with high photosynthetic efficiency. Previously microalgae species such as Arthospira, and Chlorella have been used as single-cell proteins (SCP) with limited application in pharmaceutical industries. In recent years, the demand for innovative and sustainable functional ingredients for food applications has renewed the interest worldwide in microalgae proteins. The present review aims to provide a holistic view of various aspects related to the production and processing of edible proteins from microalgae biomass. A critical review of available literature on the nutritional quality, techno-functional properties, applications in food and feed sectors, and biological activities is presented. Further, challenges associated with each stage of processing are discussed. From the literature review, it can be summarized that microalgae proteins are comparable to reference proteins both in terms of amino acid (AA) quality and techno-functional properties. However recalcitrant cell wall poses a challenge in digestibility and effective utilization of the microalgae proteins. Further, poor sensory scores and palatability of microalgae biomass limit its applications in the food and feed sector. Novel applications of microalgae proteins include meat analogues, emulsifying agents, and bioactive peptides. Development of low-cost cultivation strategies, wet biomass-based downstream processing along with the bio-refinery approach of complete biomass volarization would enhance the sustainability quotient for human food applications.

Liver Granulocytic Sarcoma With Megakaryocytic Differentiation: A Rare Extra Medullary Involvement That Warrants Liver Biopsy for Prompt Diagnosis.

Granulocytic sarcoma (GS) is an extramedullary manifestation of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms. The diagnosis depends on morphology, immunohistochemistry and flow cytometry. An unusual location of this tumor may mask its primary source, therefore, a strategy involving immediate symptom control, and investigation is crucial in preventing clinical deterioration. We present a case of a 53-year-old man who initially presented with tumor lysis syndrome and transaminitis, with a subsequent CT Scan that revealed multiple liver lesions. This case describes a rare clinical entity of granulocytic sarcoma as multiple hypoattenuating liver lesions mimicking metastatic disease in its radiographic appearance. Since the imaging features of hepatic masses are nonspecific, and considering the aggressive nature of AML with concomitant tumor lysis syndrome, a confirmatory prompt biopsy should routinely be considered.

Identifying causative mechanisms linking early-life stress to psycho-cardio-metabolic multi-morbidity: The EarlyCause project.

INTRODUCTION: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions. METHODS AND ANALYSIS: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

Socioeconomic Inequalities in Clustering of Health-Compromising Behaviours among Indian Adolescents.

BACKGROUND: The simultaneous occurrence of health-compromising behaviors can accentuate the risk of noncommunicable diseases (NCDs). This study aimed to examine the existence and patterns of clustering of four NCD risk behaviors among adolescents and its association with social position. In addition, socioeconomic inequalities in the occurrence of clustering of NCD risk behaviors were also assessed. METHODS: A cross-sectional study was undertaken among 1218 adolescents (14-19 years old) in the city of New Delhi, India. An interviewer-administered questionnaire was used to assess health-compromising behaviors (tobacco and alcohol use, fruit/vegetable intake, and physical inactivity). Clustering was assessed using pairwise correlations, counts of clustering of health-compromising behaviors, comparison of observed/expected ratios, and hierarchical agglomerative cluster analysis. Multivariable logistic regressions were used to test the associations of clustering with social position (education and wealth). The relative and slope indices of inequalities in the presence of clustering of behaviors according to education and wealth were estimated. RESULTS: Three major clusters of health behaviors emerged: (a) physical inactivity + lower fruit and vegetable intake, (b) tobacco + alcohol use, and (c) lower fruit and vegetable intake + tobacco + alcohol use. Pronounced clustering of health-compromising behaviors was observed with lower educational attainment and wealth. CONCLUSION: The presence of clustering of health-compromising behaviors was considerably higher among adolescents with lower educational attainment and wealth. The area of residence has an important influence on socioeconomic inequalities in clustering of NCD risk factors.

Understanding the cumulative risk of maternal prenatal biopsychosocial factors on birth weight: a DynaHEALTH study on two birth cohorts.

BACKGROUND: There are various maternal prenatal biopsychosocial (BPS) predictors of birth weight, making it difficult to quantify their cumulative relationship. METHODS: We studied two birth cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) born in 1985-1986 and the Generation R Study (from the Netherlands) born in 2002-2006. In NFBC1986, we selected variables depicting BPS exposure in association with birth weight and performed factor analysis to derive latent constructs representing the relationship between these variables. In Generation R, the same factors were generated weighted by loadings of NFBC1986. Factor scores from each factor were then allocated into tertiles and added together to calculate a cumulative BPS score. In all cases, we used regression analyses to explore the relationship with birth weight corrected for sex and gestational age and additionally adjusted for other factors. RESULTS: Factor analysis supported a four-factor structure, labelled closely to represent their characteristics as 'Factor1-BMI' (body mass index), 'Factor2-DBP' (diastolic blood pressure), 'Factor3-Socioeconomic-Obstetric-Profile' and 'Factor4-Parental-Lifestyle'. In both cohorts, 'Factor1-BMI' was positively associated with birth weight, whereas other factors showed negative association. 'Factor3-Socioeconomic-Obstetric-Profile' and 'Factor4-Parental-Lifestyle' had the greatest effect size, explaining 30% of the variation in birth weight. Associations of the factors with birth weight were largely driven by 'Factor1-BMI'. Graded decrease in birth weight was observed with increasing cumulative BPS score, jointly evaluating four factors in both cohorts. CONCLUSION: Our study is a proof of concept for maternal prenatal BPS hypothesis, highlighting the components snowball effect on birth weight in two different European birth cohorts.

DNA methylation links prenatal smoking exposure to later life health outcomes in offspring.

BACKGROUND: Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. METHODS: We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. RESULTS: We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10-7) associated with exposure to maternal smoking in adolescents and adults. Mendelian randomization analyses provided evidence for a causal role of four maternal smoking-related CpG sites on an increased risk of inflammatory bowel disease or schizophrenia. Further mediation analyses showed some evidence of cg25189904 in GNG12 gene mediating the effect of exposure to maternal smoking on schizophrenia-related outcomes. CONCLUSIONS: DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.

The aberrant extraction of a maxillary canine and two lower incisors.

Extractions are a common place in orthodontics. The present article discusses a rare case, in which a left maxillary canine along with two lower incisors was extracted. Atypical extractions such as these need to be duly justified and thought over before being carried out. In the case mentioned, all these teeth in question were ectopically erupted. When attempts were made to retract the canine in its right position, it exhibited gingival recession which would only go on increasing further as the distance from the transposed position in between the left central and lateral incisor to the original position was considerably large. It was planned that the 1st premolar would be converted to canine on completion of the treatment. The lower incisors too would have shown severe periodontal damage had attempts to align them was made. Not only were these two teeth lingually erupted but they also were rotated along their long axis. Derotation along with labial movement would have caused breakage of the supracrestal and transseptal fibers resulting in periodontal breakdown leading to mobility of these teeth. An esthetically and functionally balanced outcome was achieved following these extractions. In the upper arch, although the midline remained compromised, it was not worsened. In the lower arch alignment was achieved with preservation of the intercanine width. Complicated cases such as these require a thorough scrutiny of all available options. Whatever the treatment plan may be, the ultimate goal of functional and esthetic balance should be achieved.

Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults.

BACKGROUND: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. METHODS: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). FINDINGS: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10-7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10-8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. INTERPRETATION: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. FUND: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.

Socioeconomic inequalities and determinants of oral hygiene status among Urban Indian adolescents.

OBJECTIVES: To assess the socioeconomic inequalities in oral hygiene and to explore the role of various socioeconomic and psychosocial factors as determinants of these inequalities among adolescents residing in Delhi National Capital Territory. METHODS: A cross-sectional study was conducted among 1386 adolescents aged 12-15 years from three different socioeconomic groups according to their area of residence (middle-class areas, resettlement colonies and urban slum colonies). Level of oral hygiene was examined clinically using the Simplified Oral Hygiene Index (OHI-S), and an interviewer-administered questionnaire was used to measure key socio-demographic variables and psychosocial and health-related behaviours. Logistic regression analysis tested the association between area of residence and poor oral hygiene. RESULTS: Poor oral hygiene was observed in 50.2% of the adolescents. There was a socioeconomic gradient in poor oral hygiene, with higher prevalence observed at each level of deprivation. These differences were only partly explained, and the differences between adolescent groups remained statistically significant after adjusting for various demographic variables, standard of living, social capital, social support and health-affecting behaviours (OR: 1.96, 95% CI: 1.30-2.76; and OR: 2.50, 95% CI: 1.60-3.92 for adolescents from resettlement colonies and urban slums, respectively, than middle-class adolescents). CONCLUSION: Area of residence emerged as a strong socioeconomic predictor of prevalence of poor oral hygiene among Indian adolescents. Various material, psychosocial and behavioural factors did not fully explain the observed inequalities in poor oral hygiene among different adolescent groups.

Determinants of Socioeconomic Inequalities in Traumatic Dental Injuries among Urban Indian Adolescents.

OBJECTIVES: To assess socioeconomic inequalities in traumatic dental injuries (TDIs) in adolescents in New Delhi and examine the role of material, psychosocial and behavioural factors in explaining these inequalities. METHODS: We conducted a cross sectional study of 1386 adolescents aged between 12-15 years residing in three diverse areas of New Delhi. A non-invasive clinical examination was used to estimate the prevalence of TDIs, and an interviewer-administered questionnaire was used to gather relevant behavioural and socio-demographic data. Multiple logistic regression models were used to assess the association between area based socioeconomic position and TDIs. RESULTS: The overall prevalence of TDIs was 10.9%. Social inequalities in the prevalence of TDIs were observed across the adolescent population according to their area of residence. Socio-economic group differences in the prevalence of TDIs remained statistically significant after adjusting for demographic factors, material resources, social capital, social support and health affecting behaviours (OR 3.36, 95% CI 1.75-6.46 and OR 3.99, 95% CI 1.86-8.56 for adolescents from resettlement areas and urban slums respectively in comparison to middle class adolescents). Different psychosocial, material and socio-demographic variables did not attenuate the estimates for the relationship between area socioeconomic position and TDIs. CONCLUSION: Area of residence was a strong predictor of TDIs in adolescents with a higher prevalence in more deprived areas. Social inequalities in TDIs were not explained by psychosocial and behavioural variables. Health promoting policies aimed at improving the physical environment in which adolescents reside might be instrumental in reducing the prevalence of TDIs and associated inequalities.

Tungsten disulfide nanotubes reinforced biodegradable polymers for bone tissue engineering.

In this study, we have investigated the efficacy of inorganic nanotubes as reinforcing agents to improve the mechanical properties of poly(propylene fumarate) (PPF) composites as a function of nanomaterial loading concentration (0.01-0.2 wt.%). Tungsten disulfide nanotubes (WSNTs) were used as reinforcing agents in the experimental group. Single- and multi-walled carbon nanotubes (SWCNTs and MWCNTs) were used as positive controls, and crosslinked PPF composites were used as the baseline control. Mechanical testing (compression and three-point bending) shows a significant enhancement (up to 28-190%) in the mechanical properties (compressive modulus, compressive yield strength, flexural modulus and flexural yield strength) of WSNT-reinforced PPF nanocomposites compared to the baseline control. In comparison to the positive controls, significant improvements in the mechanical properties of WSNT nanocomposites were also observed at various concentrations. In general, the inorganic nanotubes (WSNTs) showed mechanical reinforcement better than (up to 127%) or equivalent to that of carbon nanotubes (SWCNTs and MWCNTs). Sol fraction analysis showed significant increases in the crosslinking density of PPF in the presence of WSNTs (0.01-0.2 wt.%). Transmission electron microscopy (TEM) analysis on thin sections of crosslinked nanocomposites showed the presence of WSNTs as individual nanotubes in the PPF matrix, whereas SWCNTs and MWCNTs existed as micron-sized aggregates. The trend in the surface area of nanostructures obtained by Brunauer-Emmett-Teller (BET) surface area analysis was SWCNTs>MWCNTs>WSNTs. The BET surface area analysis, TEM analysis and sol fraction analysis results taken together suggest that chemical composition (inorganic vs. carbon nanomaterials), the presence of functional groups (such as sulfide and oxysulfide) and individual dispersion of the nanomaterials in the polymer matrix (absence of aggregation of the reinforcing agent) are the key parameters affecting the mechanical properties of nanostructure-reinforced PPF composites and the reason for the observed increases in the mechanical properties compared to the baseline and positive controls.