Disease In Later Life Research Articles

Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being "at risk" in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

Cost-effectiveness of reducing children’s sedentary time and increasing physical activity at school: the Transform-Us! intervention

BackgroundImproving physical activity and reducing sedentary behavior represent important areas for intervention in childhood in order to reduce the burden of chronic disease related to obesity and physical inactivity in later life. This paper aims to determine the cost-effectiveness of a multi-arm primary school-based intervention to increase physical activity and/or reduce sedentary time in 8–9 year old children (Transform-Us!).MethodsModelled cost-utility analysis, using costs and effects from a cluster randomized controlled trial of a 30-month intervention that used pedagogical and environmental strategies to reduce and break up sedentary behaviour (SB-I), promote physical activity (PA-I), or a combined approach (PA + SB-I), compared to current practice. A validated multiple-cohort lifetable model (ACE-Obesity Policy model) estimated the obesity and physical activity-related health outcomes (measured as change in body mass index and change in metabolic equivalent task minutes respectively) and healthcare cost-savings over the cohort’s lifetime from the public-payer perspective, assuming the intervention was delivered to all 8–9 year old children attending Australian Government primary schools. Sensitivity analyses tested the impact on cost-effectiveness of varying key input parameters, including maintenance of intervention effect assumptions.ResultsCost-effectiveness results demonstrated that, when compared to control schools, the PA-I and SB-I intervention arms were “dominant”, meaning that they resulted in net health benefits and healthcare cost-savings if the intervention effects were maintained. When the costs and effects of these intervention arms were extrapolated to the Australian population, results suggested significant potential as obesity prevention measures (PA-I: 60,780 HALYs saved (95% UI 15,007-109,413), healthcare cost-savings AUD641M (95% UI AUD165M-$1.1B); SB-I: 61,126 HALYs saved (95% UI 11,770 − 111,249), healthcare cost-savings AUD654M (95% UI AUD126M-1.2B)). The PA-I and SB-I interventions remained cost-effective in sensitivity analysis, assuming the full decay of intervention effect after 10 years.ConclusionsThe PA-I and SB-I Transform-Us! intervention arms represent good value for money and could lead to health benefits and healthcare cost-savings arising from the prevention of chronic disease in later life if intervention effects are sustained.Trial registrationInternational Standard Randomized Controlled Trial Number (ISRCTN83725066). Australia and New Zealand Clinical Trials Registry Number (ACTRN12609000715279).

Disentangling the link between maternal influences on birth weight and disease risk in 36,211 genotyped mother–child pairs

Epidemiological studies have robustly linked lower birth weight to later-life disease risks. These observations may reflect the adverse impact of intrauterine growth restriction on a child’s health. However, causal evidence supporting such a mechanism in humans is largely lacking. Using Mendelian Randomization and 36,211 genotyped mother-child pairs from the FinnGen study, we assessed the relationship between intrauterine growth and five common health outcomes (coronary heart disease (CHD), hypertension, statin use, type 2 diabetes and cancer). We proxied intrauterine growth with polygenic scores for maternal effects on birth weight and took into account the transmission of genetic variants between a mother and a child in the analyses. We find limited evidence for contribution of normal variation in maternally influenced intrauterine growth on later-life disease. Instead, we find support for genetic pleiotropy in the fetal genome linking birth weight to CHD and hypertension. Our study illustrates the opportunities that data from genotyped parent-child pairs from a population-based biobank provides for addressing causality of maternal influences.

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life.

Neonatal stress disrupts brain development and increases the risk of neurological disorders later in life. However, the impact of neonatal stress on the development of the glymphatic system and susceptibility to Parkinson's disease (PD) remains largely unknown. Neonatal maternal deprivation (NMD) was performed on mice for 14 consecutive days to model chronic neonatal stress. Adeno-associated virus expressing A53T-α-synuclein (α-syn) was injected into the substantia nigra to establish PD model mice. Glymphatic activity was determined using invivo magnetic resonance imaging, exvivo fluorescence imaging and microplate assay. The transcription and expression of aquaporin-4 (AQP4) and other molecules were evaluated by qPCR, western blotting, and immunofluorescence. Animal's responses to NMD and α-syn overexpression were observed using behavioral tests. Glymphatic activity was impaired in adult NMD mice. AQP4 polarization and platelet-derived growth factor B (PDGF-B) signaling were reduced in the frontal cortex and hippocampus of both young and adult NMD mice. Furthermore, exogenous α-syn accumulation was increased and PD-like symptoms were aggravated in adult NMD mice. The results demonstrated that NMD could disrupt the development of the glymphatic system through PDGF-B signaling and increase the risk of PD later in life, indicating that alleviating neonatal stress could be beneficial in protecting the glymphatic system and reducing susceptibility to neurodegeneration.

Associations between diet diversity during infancy and atopic disease in later life: Systematic review

The incidence of allergic disease remains high, and many studies have focused on the association between food diversity in infancy and allergic disease later in life, but their conclusions are still controversial. We aimed to synthesize the literature on the association between childhood diet diversity and atopic disease. We searched the PubMed, Cochrane Library, Embase, Scopus, VPCS, and Wanfang databases for studies about food diversity and atopic disease. Seventeen high-quality studies, 14 cohort studies, and 1 case-control study were included from 5244 studies with sample sizes ranging from 100 to 5225. All high-quality cohort studies showed that increasing food diversity in infancy can effectively prevent the occurrence of food allergies (5/5). Moderate evidence showed that increased food diversity reduced the risk of asthma (4/6), food sensitization (3/5), and atopic dermatitis (3/5). However, its effect on eczema (5), allergic rhinitis (4), and other diseases remains controversial. Increasing food diversity during infancy is a potential method for preventing food allergy, asthma, atopic dermatitis, and food sensitization later in life. There is little or no comparative evidence about the protective effect of food diversity on other atopic diseases.

Abnormal Lipid Profile Level in Neonates and Possible Development of Atherosclerosis in Adulthood: Mini Review

The lipid profile during the neonatal period plays a pivotal role in determining the future risk of atherosclerosis and cardiovascular diseases in adulthood. Abnormal lipid levels in neonates have been associated with an increased propensity for the development of atherosclerosis later in life. This review aims to explore the significance of abnormal lipid profiles in neonates and their potential implications for the development of atherosclerosis in adulthood. The discussion encompasses the mechanisms underlying lipid metabolism in early life, the impact of various factors on lipid levels in neonates, and the long-term consequences of abnormal lipid profiles. Understanding the relationship between neonatal lipid profiles and the risk of atherosclerosis in adulthood is crucial for developing preventive strategies and interventions aimed at reducing the burden of cardiovascular diseases in later life. This review synthesizes idea from existing literature to provide insights into the importance of early lipid assessment and its implications for long-term cardiovascular health. Keywords: Abnormal Lipid Profile, Neonates, Atherosclerosis, Cardiovascular Risk, Lipid Metabolism, Early Life, Long-term Health, Preventive Strategies, Cardiovascular Disease

Association between gestational weight gain and chronic disease risks in later life

To assess the association between gestational weight gain (GWG) and the risk of developing chronic diseases in later life, this historical cohort study of 318 non-overweight women was conducted between April 2017 and November 2020 at a hospital in Tokyo. Data about GWG in the last pregnancy and the development of any chronic diseases of the subjects were retrieved from the women’s Maternal and Child Health Handbooks and through a questionnaire survey, respectively. The outcomes were chronic diseases, such as diabetes mellitus (DM), hypertension, hyperlipidemia, and being overweight (body mass index [BMI] ≥ 25 kg/m2). Association between GWG and outcomes were assessed using a logistic regression analysis.There were significant positive linear associations between GWG and the risks of developing DM, hypertension, and being overweight (P = 0.013, 0.050, and 0.017, respectively). After adjusting for later-life BMI, a significant association between GWG and DM (P = 0.025) remained, but the association between GWG and hypertension disappeared. GWG was significantly associated with DM, hypertension, and being overweight later in life. Although the association between GWG and DM was partially independent of BMI later in life, the association between GWG and hypertension was influenced by being overweight later in life.

The association between weight change patterns and obesity-related complex multimorbidity: evidence from NHANES.

Obesity is a major risk factor for non-communicable diseases (NCDs), which has been the leading cause of death nowadays. The aim of this study is to examine the association between total changes in body mass index (BMI) across adulthood and the risk of obesity-related complex multimorbidity in elderly, characterizing the capacity of BMI waves in predicting major chronic diseases. In this retrospective study, 15,520 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 and 2018. BMI was categorized as obesity (≥30.0 kg/m²), overweight (25.0-29.9 kg/m²), normal weight (18.5-24.9 kg/m²), and underweight (<18.5 kg/m²). Odds ratios (ORs) with 95% confidence interval (CIs) for the relationship between BMI change patterns and major health outcomes included hypertension, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, and population attributable fractions (PAFs) of BMI were evaluated. In comparison with participants who remained non-obese, those who are stable obese showed the highest risks of developing at least one chronic disease in later life, with odds ratios of 2.76 (95% CI: 2.20 to 3.45) from age 25 years to 10 years before baseline, 2.90 (2.28 to 3.68) from age 25 years to baseline, and 2.49 (2.11 to 2.95) in the 10-year period before baseline. Moving from non-obese to obese weight-change pattern in all periods (from age 25 years to 10 years before baseline: OR = 1.82; 95% CI, 1.57 to 2.11; from age 25 years to baseline: OR = 1.87; 95% CI, 1.59 to 2.19; from 10 years before baseline to baseline: OR = 1.62; 95% CI, 1.26 to 2.08) and moving from obese to non-obese, the 10-year period before baseline (OR = 1.89; 95% CI, 1.39 to 2.57) was associated with increased risk of chronic diseases. Midlife obesity status can explain the 8.6% risk of occurrence of the chronic diseases in elderly. Maintaining a stable healthy weight and losing weight in early adulthood and midlife are important for better life quality during the aging process. More effective strategies and policies to reduce the prevalence of obesity are needed.

Long-term health risk of offspring born from assisted reproductive technologies.

Since the world's first in vitro fertilization baby was born in 1978, there have been more than 8 million children conceived through assisted reproductive technologies (ART) worldwide, and a significant proportion of them have reached puberty or young adulthood. Many studies have found that ART increases the risk of adverse perinatal outcomes, including preterm birth, low birth weight, small size for gestational age, perinatal mortality, and congenital anomalies. However, data regarding the long-term outcomes of ART offspring are limited. According to the developmental origins of health and disease theory, adverse environments during early life stages may induce adaptive changes and subsequently result in an increased risk of diseases in later life. Increasing evidence also suggests that ART offspring are predisposed to an increased risk of non-communicable diseases, such as malignancies, asthma, obesity, metabolic syndrome, diabetes, cardiovascular diseases, and neurodevelopmental and psychiatric disorders. In this review, we summarize the risks for long-term health in ART offspring, discuss the underlying mechanisms, including underlying parental infertility, epigenetic alterations, non-physiological hormone levels, and placental dysfunction, and propose potential strategies to optimize the management of ART and health care of parents and children to eliminate the associated risks. Further ongoing follow-up and research are warranted to determine the effects of ART on the long-term health of ART offspring in later life.

Self-reported childhood adversity, unhealthy lifestyle and risk of new-onset chronic kidney disease in later life: A prospective cohort study

BackgroundThe prospective relation of childhood adversity with the risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the association of childhood adversity with new-onset CKD and examine the potential modifications by unhealthy lifestyle on this association. MethodsA total of 115,453 adults without prior CKD at baseline were included from UK Biobank (2006–2010). Childhood adversity was retrospectively evaluated through online Childhood Trauma Screener in 2016. Six common lifestyle factors including smoking, body mass index, sleep, diet, physical activity and alcohol consumption, were combined into an unhealthy lifestyle score. New-onset CKD was the primary outcome. ResultThe average age of participants in the study was 55.3 (SD, 7.7) years, and 39.3% of them were male. During a median follow-up duration of 14.1 years, 1905 participants developed new-onset CKD. Childhood adversity was significantly positively related with the risk of new-onset CKD in dose-response pattern. Each additional type of childhood adversity was associated with a 12% increment in the risk of developing CKD (adjusted hazard ratio (HR)1.12; 95% CI 1.08, 1.16). Among participants with high unhealthy lifestyle score, those with 4–5 types of childhood adversity increased the 1.73-fold risk of incident CKD (95% CI 1.17, 2.54) compared with those free of any childhood adversity. However, no statistically significant interaction was observed between unhealthy lifestyle and childhood adversity for new-onset CKD (P interaction = 0.734). ConclusionsChildhood adversity was significantly associated with an increased risk of new-onset CKD in a dose-response pattern regardless of unhealthy lifestyle.

Association of blood metal exposure with age at menarche in Korean women: KNHANES (2008–2017)

Humans are exposed to metals in their daily lives and this metal exposure is responsible for various adverse health effects. Delayed pubertal development has been suggested as an adverse outcome of metal exposure; however, evidence in nationally representative populations, especially in Asia, is limited. We evaluated the association of blood cadmium (Cd), lead (Pb), and mercury (Hg) levels with the age at menarche in Korean females whose blood heavy metals were measured as part of the Korean National Health and Nutrition Examination Survey (KNHANES) 2008–2017. Among the females 16 years of age or older, all measured heavy metals in blood, i.e., Cd, Pb, and Hg, were positively associated with age at menarche. These associations remained significant in a model adjusted for age, survey year, income, education, body mass index, smoking history, and menopausal status as covariates (β: 0.10, 95% confidence interval (CI): 0.03–0.18 for Cd; β: 0.17, 95%CI: 0.06–0.27 for Pb; β: 0.12, 95%CI: 0.05–0.19 for Hg). When the population was separated by age group at the time of the survey, the significance between heavy metal levels and age at menarche became inconsistent, but the general trends were similar. Among those in their 20s and 40s, blood Cd showed a significant association, while Pb was significant among those in their 40s and 50s. A similar trend was observed in the sensitivity analysis in the girls aged 10–15 years at the time of the survey. Blood Cd levels were associated with decreased odds of precocious menarche (OR: 0.57, 95%CI: 0.31–1.03). Delayed menarche is a risk factor for cardiovascular and chronic kidney diseases in later life; hence, public health implication of heavy metal exposure warrants a public health attention.

BUILDING BRIDGES, CATALYZING RESEARCH, EMPOWERING ALL AGES: NIA SESSION FOR EARLY-CAREER RESEARCHERS

Abstract The National Institute on Aging (NIA) at the National Institutes of Health, Department of Health and Human Services, supports biomedical and behavioral research with a lifespan focus. NIA research seeks to understand the basic processes of aging, improve prevention and treatment of diseases in later life, and improve the health of older persons, in addition to an emphasis on Alzheimer’s disease and related dementias. NIA supports a variety of training and career development opportunities for students, junior faculty, early-career investigators, and emerging scholars. In this session, we will provide an overview of NIA-funded research, followed by a presentation on funding mechanisms and strategies to consider when applying for extramural grants, particularly for early-career scientists at multiple career stages. Finally, attendees will be able to join any number of breakout group discussions (led by extramural NIA training staff and program officials) to discuss programs, initiatives, mechanisms, and/or policies specific to various career paths.

THE RELATIONSHIPS OF VOICE PROSODY MEASURES TO COGNITIVE CHANGES OVER 10 YEARS

Abstract Voice prosody measures, especially jitter and shimmer, can differentiate cognitive impairment from healthy cognition, and may be promising early biomarkers for identifying high risk before later-life disease onset. In our past work, higher jitter and lower pulse assessed during the second cognitive assessment were associated with 10-year cognitive declines in middle-age and older adults from the Midlife in the U.S. (MIDUS) study. The current study assessed voice biomarkers taken at baseline, 10 years before the second cognitive assessment, and measured voice on speech that was independent of the cognitive assessments to address the possible influence of cognitive performance on concurrent voice prosody measures. Participants (ages 34 to 82 at the first occasion) were included if they were in the Boston Longitudinal Study (BOLOS, a subset of MIDUS) and had voice measures collected from the audio recordings of the cognitive interviews. Multilevel analyses controlled for age, sex, education, race, neurological conditions, and depressive symptoms at baseline. Higher jitter, lower shimmer, and lower pulse predicted greater 10-year declines in episodic memory. Higher pitch and lower pulse were associated with greater increases in reaction time on an executive functioning task. Thus, voice biomarkers previously associated with cognitive impairment could be useful as early indicators of later-life cognitive declines. Identifying voice biomarkers that could predict 10-year cognitive change may facilitate earlier intervention for decline through modification of disease risk factors.

Single Cell RNASeq Analysis of AD and Control Post Mortem Brain Samples

Alzheimer’s disease (AD) is a devastative late life disease, molecularly characterized by biochemical lesions of amyloid β plaques and Tau tangles. the 2nd most frequent one worldwide with no early detection methods/cure. I have applied single cell sequencing and analysed post mortem brain samples (using a Chromium machine) from 2 AD and 2 control frontal cortex samples. All the samples had ethics approval, and the RNA was tested for quality. The samples were obtained from the Edenborough MRC brain bank. Very few genes have been linked to far to AD (mainly through GWAS studies [1]). Overall, I quantified about 24,000 nuclei. Using statistical, bioinformatics and computational analyses I have detected significant differential expression changes in astrocyte, neuronal and microglial marker genes. I also conducted network analyses. The percentage of reads passing filter was slightly low (68%). Overall output was a bit lower than optimal. There was still over 1.6Bn clusters generated though, which is within the specification for an S1 flow-cell, and base call quality (quality control) was excellent: 97% &gt;Q30. The read counts mapping to genome occupancy rate was also fairy low (63-81%). The number of barcodes is as follows: sample 1 (AD, Braak I-II) - 6,223 sample 2 (control) 6,262 sample 3 (AD Braak I-II) 5,332 sample 4 (AD, Braak I-II) 5,332 as well. The data is available for download under the GEO (accession number GSE175814). to assess global and cell-type specific gene expression impacts in Alzheimer’s versus control brain samples, we performed a holistic comparison of matching cell populations in AD and controls with the software cell Harmony. To identify possible gene regulatory network underlying transcriptional regulation in these distinct populations, we further explored prior evidenced transcription factor targets relationships from cell Harmony. Importantly, we observe both common and cell-type specific core transcription factors regulators, with both enriched downstream targets and regulated transcription factors. Upregulated networks in Astrocytes were associated with broad regulation by HIF1A, SOX2, NRF1, and RB1. the proportion of endothelial cells was higher in the Alzheimer’s disease samples than the neurological control samples. results reveal that the cell type-specific transcriptomic changes in Alzheimer’s disease are associated with 4 molecular pathways: angiogenesis in endothelial cells, immune response in endothelial cells and microglia, myelination in oligodendrocytes, and synaptic signalling in astrocytes and neurons. I also compared the results with microarray data from large cohort studies that examined samples from the prefrontal cortex (Alzheimer’s disease: n = 310; Neurological controls: n = 157) or temporal cortex (Alzheimer’s disease: n = 106; Neurological controls: n = 135). Among the DEGs identified in our snRNA-seq analysis, 1,113 and 764 genes were significantly differentially expressed in the microarray data from the prefrontal cortex and temporal cortex, respectively. subcluster analysis of microglia identified 13 subpopulations; VGF signalling was also found as changed. In the future, imaging of post mortem Alzheimer’s patients may verify brain cellular morphology/cell volume of vascular changes in the Alzheimer’s compared to control samples. My study findings [2] may open new venues to our understanding of the disease underlying molecular processes and cellular signaling. Regarding the glial cell changes, our main conclusion is that the glial cells may be reactive in the disease and not causal.

Cohort Profile: Better Health in Late Life.

Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population. A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization. Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

Розлади харчової поведінки дітей внаслідок стресу, спричиненого війною: загальні результати дослідження

The purpose of the study is to determine eating disorders based on the results of a survey of parents and an analysis of the perception of the behavior of children aged 5-17 in conditions of stress caused by war. Research materials and methods. A large-scale cross-sectional survey of parents of school-age children who were in Ukraine at the time of the start of the war (February 24, 2022) was conducted. A total of 5,165 parents took part in the survey. The survey concerned eating disorders and included information about the gender, age, place and conditions of the child's stay, financial support and the family's access to food, general mental manifestations of stress, eating disorders that arose as a result of military operations, changes in the child's physique, etc. The work uses a specially developed questionnaire based on standardized questionnaires about children's stress and eating disorders. This stage of the work determines the peculiarities of the child's whereabouts in relation to military events (staying in occupied territories, in close proximity to hostilities, in peaceful territory, moving within Ukraine or going abroad) and their impact on the eating behavior of school-aged children. The processing of the results included descriptive statistics, as well as the analysis of the relationships of the variables using conjugation tables by calculating the Spearman's rank coefficient and Pearson's chi-square for qualitative variables. The results. It was established that the absence or decrease of appetite, rapid satiety, change in attitude to food are general stress disorders inherent in the entire studied cohort of children. Statistical analysis revealed that the frequency and duration of eating disorders, appetite, delayed satiety, capriciousness or lack of understanding, somato-vegetative manifestations, the formation of disgust or passion for certain food products in school-age children are related to the intensity and nature of the experienced military stress. Being in occupied territories or near hostilities and subsequent displacement has the greatest impact on the frequency and duration of eating disorders. The formation of long-term eating disorders in all groups is actually a deepening of unhealthy eating habits of schoolchildren, which were demonstrated in previous studies. It is expected that these violations will lead to an increase in the frequency of chronic non-communicable diseases in later life. Conclusions. The obtained results are important for the further interpretation of the results in the framework of the study of children's eating disorders under the conditions of stress caused by the war in Ukraine and providing recommendations for the correction of the detected violations. The research has an important social significance for Ukraine, as it is aimed at solving the psychological and medical consequences of the war.

Spatial transcriptomics reveals novel genes during the remodelling of the embryonic human arterial valves.

Abnormalities of the arterial valves, including bicuspid aortic valve (BAV) are amongst the most common congenital defects and are a significant cause of morbidity as well as predisposition to disease in later life. Despite this, and compounded by their small size and relative inaccessibility, there is still much to understand about how the arterial valves form and remodel during embryogenesis, both at the morphological and genetic level. Here we set out to address this in human embryos, using Spatial Transcriptomics (ST). We show that ST can be used to investigate the transcriptome of the developing arterial valves, circumventing the problems of accurately dissecting out these tiny structures from the developing embryo. We show that the transcriptome of CS16 and CS19 arterial valves overlap considerably, despite being several days apart in terms of human gestation, and that expression data confirm that the great majority of the most differentially expressed genes are valve-specific. Moreover, we show that the transcriptome of the human arterial valves overlaps with that of mouse atrioventricular valves from a range of gestations, validating our dataset but also highlighting novel genes, including four that are not found in the mouse genome and have not previously been linked to valve development. Importantly, our data suggests that valve transcriptomes are under-represented when using commonly used databases to filter for genes important in cardiac development; this means that causative variants in valve-related genes may be excluded during filtering for genomic data analyses for, for example, BAV. Finally, we highlight "novel" pathways that likely play important roles in arterial valve development, showing that mouse knockouts of RBP1 have arterial valve defects. Thus, this study has confirmed the utility of ST for studies of the developing heart valves and broadens our knowledge of the genes and signalling pathways important in human valve development.

Comparative Analysis of the GH/IGF-1 Axis during the First Sixth Months in Children with Low Birth Weight.

To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the lower-middle São Francisco region. This is an analytical cohort and exploratory. Thirty children, were formed two groups, one of low birth weight children (LBW, n = 15) and another of normal weight (NBW = 15) were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves were measured at birth and the third and sixth months of life. Weight gain during the 6 months of follow-up in newborns with a low birth weight was greater compared to newborns with a normal birth weight. All children who were born with a low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with a low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with a low birth weight. Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with a low birth weight with greater adiposity in this group which may increase the risk of metabolic diseases in later life.

RETRACTED ARTICLE: Gender-specific determinants of overweight and obesity among older adults in India: evidence from a cross-sectional survey, 2017-18

BackgroundA major societal trend of the twenty-first century is the rapidly ageing population as a consequence of the decline in fertility and increase in life expectancy. Along with the rise in ageing population, the burden of obesity and related non-communicable diseases is also equally rising. In this study, we aimed to investigate the potential gender-specific determinants of overweight and obesity among older adults in India.Subjects and methodsThe present study used data from the Longitudinal Ageing Study in India (LASI) wave 1 (2017–18). A total sample of 25,952 older adults (≥ 60 years) was selected for the study. Descriptive statistics, bivariate chi-square test, and logistic regression estimation were applied to accomplish the study objectives. Body mass index (BMI) has been classified in this study according to the WHO criteria.ResultsThe prevalence of overweight was higher among women (18.15% in rural areas and 46.62% in urban areas) compared to men (12.9% in rural areas and 30.61% in urban areas). Similarly, obesity was higher among women than men who were residing in urban areas (17.07% vs. 5.37%), had secondary or above education (32.38% vs. 6.1%) belonged to richest strata (16.37% vs. 4.50%), or had mobility impairment (9.2% vs. 2.8%). Despite adjustment for several confounders, women were more likely to be overweight (OR: 2.18; CI: 1.86, 2.55) and obese (OR: 3.79; CI: 2.86, 5.03) than men. However, among both the elderly men and women, those who were highly educated were 2.29 times (OR: 2.29; CI: 1.80, 4.11) and 2.71 times (OR: 2.71; CI: 1.78, 4.11), respectively more likely to be overweight than their illiterate counterparts. Older adults living in urban areas were more likely to suffer from obesity compared to rural men (OR: 1.47; CI: 1.07, 2.02) and women (OR: 2.58; CI: 1.85, 3.60). Both men and women, who were highly educated were 2.64 times (OR: 2.64; CI: 1.71, 4.09) and 2.94 times (OR: 2.94; CI: 1.40, 6.20), respectively, more likely to be obese than their illiterate counterparts. Older men and women who were richest (OR: 1.60; CI: 1.19, 2.14 & OR: 2.12; CI: 1.63,2.76), or had mobility impairment (OR: 1.33; CI: 1.09,1.61 & OR: 1.72; CI: 1.42,2.08) were more likely to be overweight than their counterparts who were poorest or did not have any mobility limitation, respectively.ConclusionsThis study found increased vulnerability of overweight and obesity among older women than men irrespective of their socioeconomic, demographic, and health status. The present study suggests that introducing preventative measures such as campaigns to encourage physical activity, and community awareness may help reduce the high burden of overweight and obesity. Finally, the findings are important for better functioning of any public health programme and suitable intervention techniques to maintain a healthy body in order to lower the prevalence and risk factors of non-communicable diseases in later life.

Complications and Risks of Pregnancy, Childbirth and Offspring’s Life in Obese Women

Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically. Gestational overweight and obesity are associated with impaired outcomes for mother and child. Furthermore, studies show that maternal obesity can lead to long-term consequences in the offspring, increasing the risk for obesity and cardiometabolic disease in later life. Inflammation was altered in late pregnancy with increased activation of macrophages and increased expression of cytokine genes in the placenta, as well as increased levels of certain cytokines in the fetal bloodstream in obesity compared to pregnancies of normal weight. These changes in macrophage activation and cytokine gene expression were more pronounced and significant in the placentas accompanying male embryos. These data provide insight into placental changes in obesity and reveal potential links between placental inflammation and disease programming in the mother's obese offspring.