Aortic “Disease-in-a-Dish”: Mechanistic Insights and Drug Development Using iPSC-Based Disease Modeling

Thoracic aortic diseases, whether sporadic or due to a genetic disorder such as Marfan syndrome, lack effective medical therapies, with limited translation of treatments that are highly successful in mouse models into the clinic. Patient-derived induced pluripotent stem cells (iPSCs) offer the opportunity to establish new human models of aortic diseases. Here we review the power and potential of these systems to identify cellular and molecular mechanisms underlying disease and discuss recent advances, such as gene editing, and smooth muscle cell embryonic lineage. In particular, we discuss the practical aspects of vascular smooth muscle cell derivation and characterization, and provide our personal insights into the challenges and limitations of this approach. Future applications, such as genotype-phenotype association, drug screening, and precision medicine are discussed. We propose that iPSC-derived aortic disease models could guide future clinical trials via “clinical-trials-in-a-dish”, thus paving the way for new and improved therapies for patients

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

Thoracic aortic disease (TAD) is often silent until a life-threatening complication occurs. However, genetic information can inform both identification and treatment at an early stage. Indeed, a diagnosis is important for personalised surveillance and intervention plans, as well as cascade screening of family members. Currently, only 20% of heritable TAD patients have a causative mutation identified and, consequently, further advances in genetic coverage are required to define the remaining molecular landscape. The rapid expansion of next generation sequencing technologies is providing a huge resource of genetic data, but a critical issue remains in functionally validating these findings. Induced pluripotent stem cells (iPSCs) are patient-derived, reprogrammed cell lines which allow mechanistic insights, complex modelling of genetic disease and a platform to study aortic genetic variants. This review will address the need for iPSCs as a frontline diagnostic tool to evaluate variants identified by genomic discovery studies and explore their evolving role in biological insight through to drug discovery

Prevalence of anxiety, depression, and stress among parents of neonates admitted to neonatal intensive care unit: a systematic review and meta-analysis

Background Neonatal intensive care unit (NICU) admission causes significant distress that can hinder the successful transition into parenthood, child-parent relations, and child development. Purpose This systematic review and meta-analysis aimed to understand parental psychological phenomena. Here we assessed the emotional response of parents of newborns during NICU admission. Methods Two authors independently searched the PubMed, Cumulative Index to Nursing and Allied Health Literature, Embase, Clinical Key, and Google Scholar databases for studies published between January 01, 2004, and December 31, 2021. The review followed Cochrane collaboration guidelines and the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement. The quality of the included studies was assessed using the modified Newcastle-Ottawa Scale. Stata software (version 16) was used to compute the results. Results This review comprised 6,822 parents (5,083 mothers, 1,788 fathers; age range, 18–37 years) of NICU patients. The gestational ages and neonatal weights were 25.5–42 weeks and 750–2,920 g, respectively. The pooled prevalence of anxiety was higher among mothers (effect size [ES], 0.51; 95% confidence interval [CI], 0.41–0.61; and heterogeneity [I2]=97.1%; P<0.001) than among fathers (ES, 0.26; 95% CI, 0.11–0.42; I2=96.6%; P<0.001). Further, the pooled prevalence of depression was higher among mothers (ES, 0.31; 95% CI, 0.24–0.38; I2=91.5%; P<0.001) than among fathers (ES, 0.12; 95% CI, 0.03–0.22; I2=85.6%; P<0.001). Similarly, the pooled prevalence of stress was higher among mothers (ES, 0.41; 95% CI, 0.31–0.51; I2= 93.9%; P<0.001) than among fathers (ES, 0.22; 95% CI, 0.09–0.34; I2=85.2%; P<0.001). Conclusion NICU admission is more stressful for mothers than fathers and can affect mental health and quality of life. Mothers reported a higher pooled prevalence of stress, anxiety, and depression than fathers, possibly attributable to their feelings about birthing a sick child

Drinking Water in an Urban Area of South India

BackgroundGlobally, 1.1 billion people lack access to improved drinking water supply and drink water that is grossly contaminated. Hence, study of water treatment assumes utmost importance in order to ensure the safety of the water consumed especially in fast developing cities. This study would provide information of drinking water management practices in the study area. We studied the sources, the treatment and storage facilities of drinking water in households and assessed the free chlorine levels in the drinking water.Method  This community based cross sectional study was conducted in Mangalore - a city of Karnataka State in South India. Using convenience sampling, 100 households were visited in the area of Boloor. Information was collected regarding demographic profile, household drinking water sources, treatment and storage practices followed by testing for free chlorine in the drinking water using O-Toluidine.ResultsStudy population had high literacy rate and 83% had their main source of drinking water from municipality, 17% had private water source. Among these 6% households had bore wells, 10% had protected dug well. Overall 99% had improved source of drinking water. Sumps were present in 32% of the households.  Of these 34.4 % cleaned it once a month. Boiling was found to be the preferred choice of water treatment; but 5% of the population (lower socio economic status) did not use any method to treat water in their households. Overall, 43% households drank water by pouring to glass from storage vessel, 34% dipped glass into vessel using hands, 23% had tap system and 84.2% of the households cleaned their storage vessel daily. O-Toluidine test showed no free chlorine in drinking water in any of the homes.ConclusionStudy population had access to improved water. However households lacked appropriate storage and handling practices of drinking water which needs to be evaluated further

Community perceptions of health and chronic disease in South Indian rural transitional communities: A qualitative study

BACKGROUND: Chronic diseases are now the leading cause of death and disability worldwide; this epidemic has been linked to rapid economic growth and urbanisation in developing countries. Understanding how characteristics of the physical, social, and economic environment affect behaviour in the light of these changes is key to identifying successful interventions to mitigate chronic disease risk. DESIGN: We undertook a qualitative study consisting of nine focus group discussions (FGDs) (n=57) in five villages in rural Andhra Pradesh, South India, to understand people's perceptions of community development and urbanisation in relation to chronic disease in rural transitional communities. Specifically, we sought to understand perceptions of change linked to diet, physical activity, and pollution (because these exposures are most relevant to chronic diseases), with the aim of defining future interventions. The transcripts were analysed thematically. RESULTS: Participants believed their communities were currently less healthy, more polluted, less physically active, and had poorer access to nutritious food and shorter life expectancies than previously. There were contradictory perceptions of the effects of urbanisation on health within and between individuals; several of the participants felt their quality of life had been reduced. CONCLUSIONS: In the present study, residents viewed change and development within their villages as an inevitable and largely positive process but with some negative health consequences. Understanding how these changes are affecting populations in transitional rural areas and how people relate to their environment may be useful to guide community planning for health. Measures to educate and empower people to make healthy choices within their community may help reduce the spread of chronic disease risk factors in future years

Socio-Demographic Patterning of Physical Activity across Migrant Groups in India: Results from the Indian Migration Study

OBJECTIVE: To investigate the relationship between rural to urban migration and physical activity (PA) in India. METHODS: 6,447 (42% women) participants comprising 2077 rural, 2,094 migrants and 2,276 urban were recruited. Total activity (MET hr/day), activity intensity (min/day), PA Level (PAL) television viewing and sleeping (min/day) were estimated and associations with migrant status examined, adjusting for the sib-pair design, age, site, occupation, education, and socio-economic position (SEP). RESULTS: Total activity was highest in rural men whereas migrant and urban men had broadly similar activity levels (p<0.001). Women showed similar patterns, but slightly lower levels of total activity. Sedentary behaviour and television viewing were lower in rural residents and similar in migrant and urban groups. Sleep duration was highest in the rural group and lowest in urban non-migrants. Migrant men had considerably lower odds of being in the highest quartile of total activity than rural men, a finding that persisted after adjustment for age, SEP and education (OR 0.53, 95% CI 0.37, 0.74). For women, odds ratios attenuated and associations were removed after adjusting for age, SEP and education. CONCLUSION: Our findings suggest that migrants have already acquired PA levels that closely resemble long-term urban residents. Effective public health interventions to increase PA are needed

Dietary Intake and Rural-Urban Migration in India: A Cross-Sectional Study

BACKGROUND: Migration from rural areas of India contributes to urbanisation and lifestyle change, and dietary changes may increase the risk of obesity and chronic diseases. We tested the hypothesis that rural-to-urban migrants have different macronutrient and food group intake to rural non-migrants, and that migrants have a diet more similar to urban non-migrants. METHODS AND FINDINGS: The diets of migrants of rural origin, their rural dwelling sibs, and those of urban origin together with their urban dwelling sibs were assessed by an interviewer-administered semi-quantitative food frequency questionnaire. A total of 6,509 participants were included. Median energy intake in the rural, migrant and urban groups was 2731, 3078, and 3224 kcal respectively for men, and 2153, 2504, and 2644 kcal for women (p<0.001). A similar trend was seen for overall intake of fat, protein and carbohydrates (p<0.001), though differences in the proportion of energy from these nutrients were <2%. Migrant and urban participants reported up to 80% higher fruit and vegetable intake than rural participants (p<0.001), and up to 35% higher sugar intake (p<0.001). Meat and dairy intake were higher in migrant and urban participants than rural participants (p<0.001), but varied by region. Sibling-pair analyses confirmed these results. There was no evidence of associations with time in urban area. CONCLUSIONS: Rural to urban migration appears to be associated with both positive (higher fruit and vegetables intake) and negative (higher energy and fat intake) dietary changes. These changes may be of relevance to cardiovascular health and warrant public health interventions