Adolescent behavioral problems, preterm/low birth weight children and adult life success in a prospective Australian birth cohort study.

BACKGROUND: Preterm and/or low birthweight (PT/LBW) is predictive of a range of adverse adult outcomes, including lower employment, educational attainment, and mental wellbeing, and higher welfare receipt. Existing studies, however, on PT/LBW and adult psychosocial risks are often limited by low statistical power. Studies also fail to examine potential child or adolescent pathways leading to later adult adversity. Using a life course framework, we examine how adolescent problem behaviors may moderate the association between PT/LBW and a multidimensional measure of life success at age 30 to potentially address these limitations. METHODS: We analyze 2044 respondents from a Brisbane, Australia cohort followed from birth in1981-1984 through age 30. We examine moderation patterns using obstetric birth outcomes for weight and gestation, measures of problem behaviors from the Child Behavioral Checklist at age 14, and measures of educational attainment and life success at 30 using multivariable normal and ordered logistic regression. RESULTS: Associations between PT/LBW and life success was found to be moderated by adolescent problem behaviors in six scales, including CBCL internalizing, externalizing, and total problems (all p < 0.01). In comparison, associations between LBW and educational attainment illustrate how a single-dimensional measure may yield null results. CONCLUSION: For PT/LBW, adolescent problem behaviors increase risk of lower life success at age 30. Compared to analysis of singular outcomes, the incorporation of multidimensional measures of adult wellbeing, paired with identification of risk and protective factors for adult life success as children develop over the lifespan, may further advance existing research and interventions for PT/LBW children.

The trifecta of adulthood: Housing, partnering and childbearing trajectories.

Substantial changes in residential transitions and family formation patterns have been observed in Western societies, but less attention has been paid to the de-standardisation of adulthood pathways in East Asian contexts, where unique social, economic and cultural circumstances may produce diverse trajectories that are less explored in existing theoretical and empirical frameworks. Adopting a life course perspective, this study identifies the multi-trajectories of housing, partnering and childbearing across adulthood in Taiwan, a setting marked by high housing costs and low fertility rates. Data from the Taiwanese Panel Study of Family Dynamics 2000-2020 (N = 6,931) were used for group-based trajectory modelling, and mixed-effects multinomial regression was employed to examine the likelihood of group membership given early-life resources and social origin. Six common housing-partnering-childbearing trajectories were identified. The most prevalent living arrangement was living in parental homes (50.7%), followed by rental homes (25%), self-owned homes (15.5%) and dorms or other (8.8%). Union formation generally precedes childbearing, whereas housing transitions may occur at various time points. Young adults' home-leaving and homeownership access appear to be closely related to their parental backgrounds, such as their parents' educational attainment and occupational status. Overall, the findings are consistent with the de-standardisation of pathways to adulthood, demonstrating the diversity in adult trajectories and the lack of a single dominant pattern.

Immune and pathophysiologic profiling of antenatal coronavirus disease 2019 in the GIFT cohort: A Singaporean case-control study.

COVID-19 can be severe in pregnant women, and have adverse consequences for the subsequent infant. We profiled the post-infectious immune responses in maternal and child blood as well as breast milk in terms of antibody and cytokine expression and performed histopathological studies on placentae obtained from mothers convalescent from antenatal COVID-19. Seventeen mother-child dyads (8 cases of antenatal COVID-19 and 9 healthy unrelated controls; 34 individuals in total) were recruited to the Gestational Immunity For Transfer (GIFT) study. Maternal and infant blood, and breast milk samples were collected over the first year of life. All samples were analyzed for IgG and IgA against whole SARS-CoV-2 spike protein, the spike receptor-binding domain (RBD), and previously reported immunodominant epitopes, as well as cytokine levels. The placentae were examined microscopically. The study is registered at clinicaltrials.gov under the identifier NCT04802278. We found high levels of virus-specific IgG in convalescent mothers and similarly elevated titers in newborn children. Thus, antenatal SARS-CoV-2 infection led to high plasma titers of virus-specific antibodies in infants postnatally. However, this waned within 3-6 months of life. Virus neutralization by plasma was not uniformly achieved, and the presence of antibodies targeting known immunodominant epitopes did not assure neutralization. Virus-specific IgA levels were variable among convalescent individuals' sera and breast milk. Antibody transfer ratios and the decay of transplacentally transferred virus-specific antibodies in neonatal circulation resembled that for other pathogens. Convalescent mothers showed signs of chronic inflammation marked by persistently elevated IL17RA levels in their blood. Four placentae presented signs of acute inflammation, particularly in the subchorionic region, marked by neutrophil infiltration even though > 50 days had elapsed between virus clearance and delivery. Administration of a single dose of BNT162b2 mRNA vaccine to mothers convalescent from antenatal COVID-19 increased virus-specific IgG and IgA titers in breast milk, highlighting the importance of receiving the vaccine even after natural infection with the added benefit of enhanced passive immunity.

Educational differentials on the transition to first birth in South Korea.

Drawing on two competing frameworks, the leader-follower model and the permanent-difference model, this study examines the educational gradient in the transition to first birth across birth cohorts in South Korea. The leader-follower model suggests that low fertility behaviour would spread from more educated women to their less educated counterparts, whereas the permanent-difference model posits that the gaps in fertility between education groups would remain distinct over time. Using nationally representative panel data of 7914 women (130,078 person-years) born between 1960 and 1984, results from discrete-time survival analysis show an initial convergence of gaps in fertility between education groups, but the gaps are now re-emerging and widening. Substantial gaps in fertility are found in younger birth cohorts born between 1975 and 1984. The convergence-divergence pattern observed over time highlights the importance of recognising how women's changing educational profile affects fertility in an ultra-low fertility setting.

Parkinson's Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1.

Parkinson's disease (PD) is a debilitating movement disorder characterised by the loss of dopaminergic neurons in the substantia nigra. As neuroprotective agents mitigating the rate of neurodegeneration are unavailable, the current therapies largely focus only on symptomatic relief. Here, we identified stress-inducible phosphoprotein 1 (STIP1) as a putative neuroprotective factor targeted by PD-specific autoantibodies. STIP1 is a co-chaperone with reported neuroprotective capacities in mouse Alzheimer's disease and stroke models. With human dopaminergic neurons derived from induced pluripotent stem cells, STIP1 was found to alleviate staurosporine-induced neurotoxicity. A case-control study involving 50 PD patients (average age = 62.94 ± 8.48, Hoehn and Yahr >2 = 55%) and 50 age-matched healthy controls (HCs) (average age = 63.1 ± 8) further revealed high levels of STIP1 autoantibodies in 20% of PD patients compared to 10% of HCs. Using an overlapping peptide library covering the STIP1 protein, we identified four PD-specific B cell epitopes that were not recognised in HCs. All of these epitopes were located within regions crucial for STIP1's chaperone function or prion protein association. Our clinical and neuro-immunological studies highlight the potential of the STIP1 co-chaperone as an endogenous neuroprotective agent in PD and suggest the possible involvement of autoimmune mechanisms via the production of autoantibodies in a subset of individuals.

New Insights into Immune-Mediated Mechanisms in Parkinson's Disease.

The immune system has been increasingly recognized as a major contributor in the pathogenesis of Parkinson's disease (PD). The double-edged nature of the immune system poses a problem in harnessing immunomodulatory therapies to prevent and slow the progression of this debilitating disease. To tackle this conundrum, understanding the mechanisms underlying immune-mediated neuronal death will aid in the identification of neuroprotective strategies to preserve dopaminergic neurons. Specific innate and adaptive immune mediators may directly or indirectly induce dopaminergic neuronal death. Genetic factors, the gut-brain axis and the recent identification of PD-specific T cells may provide novel mechanistic insights on PD pathogenesis. Future studies to address the gaps in the identification of autoantibodies, variability in immunophenotyping studies and the contribution of gut dysbiosis to PD may eventually provide new therapeutic targets for PD.

A framework for building cognitive process models.

The term process model is widely used, but rarely agreed upon. This paper proposes a framework for characterizing and building cognitive process models. Process models model not only inputs and outputs but also model the ongoing information transformations at a given level of abstraction. We argue that the following dimensions characterize process models: They have a scope that includes different levels of abstraction. They specify a hypothesized mental information transformation. They make predictions not only for the behavior of interest but also for processes. The models' predictions for the processes can be derived from the input, without reverse inference from the output data. Moreover, the presumed information transformation steps are not contradicting current knowledge of human cognitive capacities. Lastly, process models require a conceptual scope specifying levels of abstraction for the information entering the mind, the proposed mental events, and the behavior of interest. This framework can be used for refining models before testing them or after testing them empirically, and it does not rely on specific modeling paradigms. It can be a guideline for developing cognitive process models. Moreover, the framework can advance currently unresolved debates about which models belong to the category of process models.

Improving judgment accuracy by sequential adjustment.

Judging an object's value based on relevant cues can be challenging. We propose a simple method to improve judgment accuracy: Instead of estimating a value after seeing all available cues simultaneously, individuals view cues sequentially, one after another, making and adjusting their estimate at each step. The sequential procedure may alleviate computational difficulties in cue integration, leading to higher judgment accuracy. We tested this hypothesis in two real-world tasks in which participants judged either the price of diamonds or the fuel economy of cars. Two studies with professional jewelers and car salespeople show that most participants indeed judged more accurately with a sequential than with a simultaneous procedure. Another two studies with college students further support this finding and show additionally that the sequential procedure could raise the judgment accuracy of inexperienced students to the same level as that of professionals judging with the simultaneous procedure.

Postnatal Deletion of Fat Storage-inducing Transmembrane Protein 2 (FIT2/FITM2) Causes Lethal Enteropathy.

Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that store neutral lipids within a phospholipid monolayer. LDs compartmentalize lipids and may help to prevent cellular damage caused by their excess or bioactive forms. FIT2 is a ubiquitously expressed transmembrane endoplasmic reticulum (ER) membrane protein that has previously been implicated in LD formation in mammalian cells and tissue. Recent data indicate that FIT2 plays an essential role in fat storage in an in vivo constitutive adipose FIT2 knock-out mouse model, but the physiological effects of postnatal whole body FIT2 depletion have never been studied. Here, we show that tamoxifen-induced FIT2 deletion using a whole body ROSA26CreER(T2)-driven FIT2 knock-out (iF2KO) mouse model leads to lethal intestinal pathology, including villus blunting and death of intestinal crypts, and loss of lipid absorption. iF2KO mice lose weight and die within 2 weeks after the first tamoxifen dose. At the cellular level, LDs failed to form in iF2KO enterocytes after acute oil challenge and instead accumulated within the ER. Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO mice, leading to the buildup of bile acids within enterocytes. These data support the conclusion that FIT2 plays an essential role in regulating intestinal health and survival postnatally.

Recent advances in understanding proteins involved in lipid droplet formation, growth and fusion.

Lipid droplets (LDs) were once viewed as simple, inert lipid micelles. However, they are now known to be organelles with a rich proteome involved in a myriad of cellular processes. LDs are heterogeneous in nature with different sizes and compositions of phospholipids, neutral lipids and proteins. This review takes a focused look at the roles of proteins involved in the regulation of LD formation, expansion, and morphology. The related proteins are summarized such as the fat-specific protein (Fsp27), fat storage-inducing transmembrane (FIT) proteins, seipin and ADP-ribosylation factor 1-coat protein complex I (Arf-COPI). Finally, we present important challenges in LD biology for a deeper understanding of this dynamic organelle to be achieved.

Fat storage-inducing transmembrane protein 2 is required for normal fat storage in adipose tissue.

Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo.

Validity of dietary diversity score as an indicator of nutrient adequacy among older adults in Pasay City, Philippines

OBJECTIVE:The study was conducted to determine the validity of Dietary Diversity Score (DDS) as an alternative indicator for nutrient adequacy among older adults in Pasay City, Philippines.METHODS: An analytic cross sectional study design was used on a representative sample of older adults (n = 82) in all barangays under the Doña Marta Health Center in Pasay City. A 5-stage multiple pass single 24-hour food recall was performed to determine the dietary intake of each respondent. Subject's nutrient intake was obtained using the FCT+Menu Eval software. Nutrient Adequacy Ratio (NAR) was then computed using the ratio of subject's nutrient intake to the Recommended Energy and Nutrient Intakes (RENI) for Filipinos.  The Mean Adequacy Ratio (MAR) was then obtained by computing for the average of the NARs, expressed as a ratio ranging from 0 - 1. Dietary Diversity Score was calculated using the DDS Questionnaire recommended by the FAO Guideline. For the statistical analysis, Pearson's correlation was used to determine the relationship between MAR and DDS. ROC curve analysis was done to determine the most appropriate cut-off points for using DDS among the older adults.RESULTS: The selected older adults of Pasay City had a mean DDS of 4.15 (0.14) and a mean MAR of 0.64 (0.02). There was a significant and strong correlation between MAR and DDS (r = 0.519; P CONCLUSION: DDS may be used as an indicator of nutrient adequacy among the randomly selected older adults.