Fertility Intentions During the Covid-19 Pandemic: An Analysis of Individual- and Municipality-Level Determinants.

Recognizing the prolonged, uneven, and evolving nature of the Covid-19 pandemic, this study provides one of the first dynamic, multilevel perspectives of women's fertility intentions in response to the pandemic and its multifaceted impacts. We examine how evolving individual- and community-level Covid-19 risk mechanisms and socioeconomic and life-course conditions are associated with continuity and change in women's fertility intentions. We combine individual-level panel data from a population-based sample of women aged 18-34 in Pernambuco, Brazil in 2020 and 2021 with corresponding administrative data from 94 municipalities. We use multinomial logit regressions to model continuity and change in fertility intentions across waves. We then estimate fixed effect models to highlight the time-varying determinants of changing fertility intentions while accounting for unobserved, time-invariant individual factors. We find that high and/or increasing individual and community-level Covid-19 exposure is associated with a greater likelihood of abandoning initial childbearing plans and a greater likelihood to maintain intentions to forego versus to intend having additional children. We advance the literature by highlighting how individual-level Covid-19 infection risk perceptions matter for fertility intentions, net of community-level exposure, and the necessity of dynamic perspectives for understanding how fertility intentions have changed (or not) in response to the pandemic.

Diet-induced obesity mediated through Estrogen-Related Receptor α is independent of intestinal function.

Obesity has become an epidemic, prompting advances in therapies targeting this condition. Estrogen-related receptor α (ESRRA), a transcription factor, plays pivotal roles in energy metabolism across diverse tissues. Studies have demonstrated that loss of Esrra leads to fat malabsorption and resistance to diet-induced obesity. However, the reliance of these studies on germline Esrra mutants overlooks the tissue-specific implications of ESRRA in diet-induced obesity. Notably, Esrra exhibits high expression in the gastrointestinal (GI) tract relative to other tissues. Given the critical role of the GI tract in dietary lipid metabolism, this study employs mouse genetics and genomics approaches to dissect the specific impact of intestinal ESRRA along with investigating its role in diet-induced obesity.

iTRAQ-based mass spectrometry screen to identify serum biomarkers in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder with no reliable serum biomarkers currently available other than autoantibodies. METHODS: In the present study, isobaric tags for relative and absolute quantitation-based mass spectrometry was used to screen the sera of patients with SLE to uncover potential disease biomarkers. RESULTS: 85 common proteins were identified, with 16 being elevated (≥1.3) and 23 being decreased (≤0.7) in SLE. Of the 16 elevated proteins, serum alpha-1-microglobulin/bikunin precursor (AMBP), zinc alpha-2 glycoprotein (AZGP) and retinol-binding protein 4 (RBP4) were validated in independent cross-sectional cohorts (Cohort I, N=52; Cohort II, N=117) using an orthogonal platform, ELISA. Serum AMBP, AZGP and RBP4 were validated to be significantly elevated in both patients with inactive SLE and patients with active SLE compared with healthy controls (HCs) (p<0.05, fold change >2.5) in Cohort I. All three proteins exhibited good discriminatory power for distinguishing active SLE and inactive SLE (area under the curve=0.82-0.96), from HCs. Serum AMBP exhibited the largest fold change in active SLE (5.96) compared with HCs and correlated with renal disease activity. The elevation in serum AMBP was validated in a second cohort of patients with SLE of different ethnic origins, correlating with serum creatinine (r=0.60, p<0.001). CONCLUSION: Since serum AMBP is validated to be elevated in SLE and correlated with renal disease, the clinical utility of this novel biomarker warrants further analysis in longitudinal cohorts of patients with lupus and lupus nephritis.

Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.

Terminal differentiation requires massive restructuring of the transcriptome. During intestinal differentiation, the expression patterns of nearly 4,000 genes are altered as cells transition from progenitor cells in crypts to differentiated cells in villi. We identify dynamic occupancy of RNA polymerase II (Pol II) to gene promoters as the primary driver of transcriptomic shifts during intestinal differentiation in vivo. Changes in enhancer-promoter looping interactions accompany dynamic Pol II occupancy and are dependent upon HNF4, a pro-differentiation transcription factor. Using genetic loss-of-function, chromatin immunoprecipitation sequencing (ChIP-seq), and immunoprecipitation (IP) mass spectrometry, we demonstrate that HNF4 collaborates with chromatin remodelers and loop-stabilizing proteins and facilitates Pol II occupancy at hundreds of genes pivotal to differentiation. We also explore alternate mechanisms that drive differentiation gene expression and find that pause-release of Pol II and post-transcriptional mRNA stability regulate smaller subsets of differentially expressed genes. These studies provide insights into the mechanisms of differentiation in renewing adult tissue.

Dynamic RNA Polymerase II Recruitment Drives Differentiation of the Intestine under the direction of HNF4.

Terminal differentiation requires a massive restructuring of the transcriptome. During intestinal differentiation, the expression patterns of nearly 4000 genes are altered as cells transition from progenitor cells in crypts to differentiated cells in villi. We identified dynamic recruitment of RNA Polymerase II (Pol II) to gene promoters as the primary driver of transcriptomic shifts during intestinal differentiation in vivo. Changes in enhancer-promoter looping interactions accompany dynamic Pol II recruitment and are dependent upon HNF4, a pro-differentiation transcription factor. Using genetic loss-of- function, ChIP-seq and IP mass spectrometry, we demonstrate that HNF4 collaborates with chromatin remodelers and loop-stabilizing proteins and facilitates Pol II recruitment at hundreds of genes pivotal to differentiation. We also explore alternate mechanisms which drive differentiation gene expression and find pause-release of Pol II and post- transcriptional mRNA stability regulate smaller subsets of differentially expressed genes. These studies provide insights into the mechanisms of differentiation in a renewing adult tissue.

Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.

BACKGROUND: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate. METHODS: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice. RESULTS: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts. CONCLUSIONS: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

Measuring Fertility Intentions During Times of Crisis: An Example Using Survey Data Amid the Covid-19 Pandemic.

Fertility intentions-intentions regarding whether and when to have children-predict reproductive health outcomes. Measuring fertility intentions is difficult, particularly during macrostructural shocks, for at least two reasons: (1) fertility intentions may be especially volatile during periods of uncertainty and (2) macrostructural shocks may constrain data collection. We propose a set of indicators that capture how a macrostructural shock directly alters fertility intentions, with a particular focus on the Coronavirus disease 2019 (Covid-19) pandemic. We advance the conceptualization and construct of fertility intentions measures in three ways. First, we demonstrate the value of direct questions about whether women attributed changes in fertility intentions to the pandemic. Second, we highlight the importance of a typology that delineates fertility postponement, advancement, foregoing, and indecision. Third, we demonstrate the importance of incorporating a granular time window within a two-year period to capture short-term changes to fertility intentions. We exemplify the value of our proposed measures using survey data from a probabilistic sample of women aged 18-34 in Pernambuco, Brazil. We discuss the self-reported change in intentions due to Covid in wave 1 as well as panel change across waves. We further ground our contributions by uncovering important variations by social origin and parity.

ChatGPT-Exploring Its Role in Clinical Chemistry.

OBJECTIVE: To evaluate the utility of artificial intelligence-powered language models (ChatGPT 3.5 and GPT-4) compared to trainees and clinical chemists in responding to common laboratory questions in the broad area of Clinical Chemistry. METHODS: 35 questions from real-life case scenarios, clinical consultations, and clinical chemistry testing questions were used to evaluate ChatGPT 3.5, and GPT-4 alongside clinical chemistry trainees (residents/fellows) and clinical chemistry faculty. The responses were scored based on category and based on years of experience. RESULTS: The Senior Chemistry Faculty demonstrated superior accuracy with 100% of correct responses compared to 90.5%, 82.9%, and 71.4% of correct responses from the junior chemistry faculty, fellows, and residents respectively. They all outperformed both ChatGPT 3.5 and GPT-4 which generated 60% and 71.4% correct responses respectively. Of the sub-categories examined, ChatGPT 3.5 achieved 100% accuracy in endocrinology while GPT-4 did not achieve 100% accuracy in any subcategory. GPT-4 was overall better than ChatGPT 3.5 by generating similar correct responses as residents (71.4%) but performed poorly to human participants when both partially correct and incorrect indices were considered. CONCLUSION: Despite all the advances in AI-powered language models, ChatGPT 3.5 and GPT-4 cannot replace a trained pathologist in answering clinical chemistry questions. Caution should be observed by people, especially those not trained in clinical chemistry, to interpret test results using chatbots.

Bride price, dowry, and young men with time to kill: A commentary on men's marriage postponement in India.

Rising numbers of young unmarried men in India reflect a marriage squeeze that goes beyond the shortage of brides created by sex-selective abortion. We describe a decline in men's marriageability caused by their falling economic prospects at the same time as families of brides are increasingly seeking grooms with stable employment. We group young men into those without jobs or much education, those with education but no work, and the privileged few with education as well as employment. This classification resolves some of the seeming contradictions in the qualitative literature on marriage in India. Some of this literature talks about the rising prevalence of bride price and some about the persistence of dowry, while some papers reflect in general on the costs of being young, male, and aimless. Our commentary includes a review of the growing literature on the physiological and (perhaps) consequently behavioural and health outcomes of men's anomie.

Bacterial RF3 senses chaperone function in co-translational folding.

Molecular chaperones assist with protein folding by interacting with nascent polypeptide chains (NCs) during translation. Whether the ribosome can sense chaperone defects and, in response, abort translation of misfolding NCs has not yet been explored. Here we used quantitative proteomics to investigate the ribosome-associated chaperone network in E. coli and the consequences of its dysfunction. Trigger factor and the DnaK (Hsp70) system are the major NC-binding chaperones. HtpG (Hsp90), GroEL, and ClpB contribute increasingly when DnaK is deficient. Surprisingly, misfolding because of defects in co-translational chaperone function or amino acid analog incorporation results in recruitment of the non-canonical release factor RF3. RF3 recognizes aberrant NCs and then moves to the peptidyltransferase site to cooperate with RF2 in mediating chain termination, facilitating clearance by degradation. This function of RF3 reduces the accumulation of misfolded proteins and is critical for proteostasis maintenance and cell survival under conditions of limited chaperone availability.

Offspring's labor migration and its implications for elderly parents' emotional wellbeing in Indonesia.

Population ageing and labor out-migration are increasingly challenging normative intergenerational support systems and familial welfare in parts of Asia. Extant studies look at how migration affects the material wellbeing of sending-households, but less is known about how migration shapes the emotional health of non-migrants as origin and destination conditions evolve. This study examines how labor migration among adult children shape the emotional health of elderly parents in Indonesia, and how observed implications are modified by alternative care arrangements and different migrant destinations. Using panel data from 2101 respondents age 50+ in the 2007 and 2014 Indonesia Family Life Survey, and individual-level fixed effects regressions, this study finds that offspring's migration is associated with increased parental depression, net of covariates. Depressive outcomes are abated if resulting care deficits are offset by co-residence or daily interactions with adult children, or if children move to economically lucrative international destinations; however, having a child in Malaysia - a destination characterized by high informal labor employment - increased parental depression. These findings draw attention to the non-economic implications of migration and the distress experienced specifically by parents who lack intergenerational support and who have concerns about child's wellbeing at destination.

A novel synthesis of trans-unsaturated fatty acids by the Gram-positive commensal bacterium Enterococcus faecalis FA2-2.

A key mechanism of Pseudomonas spp. adaptation to environmental stressors is their ability to convert the cis-unsaturated fatty acids of the membrane lipids to their trans-isomers to rigidify the membrane and thereby resist stresses. Although this Cti-catalyzed enzymatic isomerization has been well investigated in the P. putida paradigm, several bacterial species have been found to produce trans-unsaturated fatty acids. Although cti orthologs have only been reported in Gram-negative bacteria, we report that E. faecalis FA2-2 cultures synthesize trans-unsaturated fatty acids during growth by a mechanism similar of P. putida. Although the role of trans-unsaturated fatty acids (trans-UFAs) in E. faecalis remains obscure, our results indicate that organic solvents, as well as the membrane altering antibiotic, daptomycin, had no effect on trans-UFA formation in E. faecalis FA2-2. Moreover trans-UFA production in E. faecalis FA2-2 membranes was constant in oxidative stress conditions or when metal chelator EDTA was added, raising the question about the role of heme domain in cis-trans isomerization in E. faecalis FA2-2. Although growth temperature and growth phase had significant effects on cis-trans isomerization, the bulk physical properties of the membranes seems unlikely to be altered by the low levels of trans-UFA. Hence, any effects seems likely to be on membrane proteins and membrane enzyme activities. We also report investigations of cti gene distribution in bacteria was and suggest the distribution to be triggered by habitat population associations. Three major Cti clusters were defined, corresponding to Pseudomonas, Pseudoalteromonas and Vibrio Cti proteins.

Tracing the development of psychosocial rehabilitation from its origin to the current with emphasis on the Indian context.

Mental illness and mental health are concepts that have existed from time immemorial. In India, the Atharvaveda and Vedic texts and traditional medical systems such as Siddha, Unani, and Ayurveda have described mental health and disorders, in detail. The advent of the mental hospital brought in the 'chemical revolution' in psychiatric management. The early nineties witnessed the birth of psychiatric rehabilitation in India. These developments saw a shift from a biological to a biopsychosocial model. It embraced the individual, family, community and society into the treatment process. The present rehabilitation process is geared towards providing quality of life, community living, accessible and suitable care.