Interactions between Maternal Prenatal Obesity and Physiological Stress: Predictors of Offspring Adult Obesity

Over half of US women of childbearing age are overweight or obese. This is significant because excessive gestational maternal weight may program offspring for greater risk of lifetime obesity. Preliminary research suggests this effect may be moderated by fetal exposure to stress hormones, known to be dysregulated in obese individuals. However, long-term longitudinal research of these constructs is needed. Therefore, this study used archival data from the NEFS/CPP Studies to examine interactions between maternal pre-pregnancy BMI/gestational weight gain and fetal cortisol exposure as predictors of offspring growth trajectories from birth-7 years and adult BMI via growth curve modeling and ANOVAs. We predict that offspring born to mothers who were obese prior to conception, or who gained an excessive amount of weight during gestation, will show associations between greater cortisol exposure during the third trimester and both steeper growth trajectories in childhood and greater BMI as adults. Results would highlight modifiable maternal risk factors to target for education and intervention for women of childbearing age to prevent adverse cardiometabolic outcomes in offspring

Changes in species composition and diversity of a montane beetle community over the last millennium in the High Tatras, Slovakia : Implications for forest conservation and management

Montane biomes are niche environments high in biodiversity with a variety of habitats. Often isolated, these non-continuous remnant ecosystems inhabit narrow ecological zones putting them under threat from changing climatic conditions and anthropogenic pressure. Twelve sediment cores were retrieved from a peat bog in Tatra National Park, Slovakia, and correlated to each other by wiggle-matching geochemical signals derived from micro-XRF scanning, to make a reconstruction of past conditions. A fossil beetle (Coleoptera) record, covering the last 1000 years at 50- to 100-year resolution, gives a new insight into changing flora and fauna in this region. Our findings reveal a diverse beetle community with varied ecological groups inhabiting a range of forest, meadow and synanthropic habitats. Changes in the beetle community were related to changes in the landscape, driven by anthropogenic activities. The first clear evidence for human activity in the area occurs c. 1250 CE and coincides with the arrival of beetle species living on the dung of domesticated animals (e.g. Aphodius spp.). From 1500 CE, human (re)settlement, and activities such as pasturing and charcoal burning, appear to have had a pronounced effect on the beetle community. Local beetle diversity declined steadily towards the present day, likely due to an infilling of the forest hollow leading to a decrease in moisture level. We conclude that beetle communities are directly affected by anthropogenic intensity and land-use change. When aiming to preserve or restore natural forest conditions, recording their past changes in diversity can help guide conservation and restoration. In doing so, it is important to look back beyond the time of significant human impact, and for this, information contained in paleoecological records is irreplaceable.Peer reviewe

Supporting caregivers of veterans with Alzheimer’s disease and traumatic brain injury: study protocol for a randomized controlled trial

Background: Patients with Alzheimer's disease and related dementias (ADRD) and traumatic brain injury (TBI) and their caregivers require cognitive and behavioral symptom management, interdisciplinary care, support for caregivers, and seamless care coordination between providers. Caring for someone with ADRD or TBI is associated with higher rates of psychological morbidity and burden, social isolation, financial hardship, and deterioration of physical health. Tremendous need exists for primary care-based interventions that concurrently address the care needs of dyads and aim to improve care and outcomes for both individuals with ADRD and TBI and their family caregivers. Methods: The Aging Brain Care Acquiring New Skills While Enhancing Remaining Strengths (ABC ANSWERS) study is a randomized controlled trial that tests the effectiveness of an intervention based on two evidence-based programs that have been developed for and previously tested in populations with ADRD, TBI, stroke, and late-life depression and/or who have survived an intensive care unit stay. This study includes 200 dyads comprised of a veteran with a diagnosis of ADRD or TBI and the veteran's primary informal caregiver. Dyads are randomized to receive the ABC ANSWERS intervention or routine Veterans Health Administration (VHA) primary care with a standardized educational and resource information packet. Data collection occurs at baseline and three follow-up time points (3 months, 6 months, and 12 months). The primary outcome is caregiver quality of life (QoL). A secondary measure for the caregiver is caregiver burden. Secondary measures for both the veteran and caregiver include symptoms of depression and anxiety. Discussion: The ABC ANSWERS intervention integrates common features of an evidence-based collaborative care model for brain health while concurrently attending to the implementation barriers of delivering care and skills to dyads. We hypothesize that caregivers in dyads randomized to the ABC ANSWERS program will experience higher levels of QoL and lower levels of depression, anxiety, dyadic strain, and caregiver burden at 12 months than those receiving usual VHA primary care

cGMP-dependent protein kinase Iα associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake

<p>Abstract</p> <p>Background</p> <p>The Na⁺/Cl^--dependent serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) is a critical element in neuronal 5-HT signaling, being responsible for the efficient elimination of 5-HT after release. SERTs are not only targets for exogenous addictive and therapeutic agents but also can be modulated by endogenous, receptor-linked signaling pathways. We have shown that neuronal A3 adenosine receptor activation leads to enhanced presynaptic 5-HT transport <it>in vitro </it>and an increased rate of SERT-mediated 5-HT clearance <it>in vivo</it>. SERT stimulation by A3 adenosine receptors derives from an elevation of cGMP and subsequent activation of both cGMP-dependent protein kinase (PKG) and p38 mitogen-activated protein kinase. PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear.</p> <p>Results</p> <p>In this report, we explore the kinase isoform specificity underlying the rapid stimulation of SERT activity by PKG activators. Using immortalized, rat serotonergic raphe neurons (RN46A) previously shown to support 8-Br-cGMP stimulation of SERT surface trafficking, we document expression of PKGI, and to a lower extent, PKGII. Quantitative analysis of staining profiles using permeabilized or nonpermeabilized conditions reveals that SERT colocalizes with PKGI in both intracellular and cell surface domains of RN46A cell bodies, and exhibits a more restricted, intracellular pattern of colocalization in neuritic processes. In the same cells, SERT demonstrates a lack of colocalization with PKGII in either intracellular or surface membranes. In keeping with the ability of the membrane permeant kinase inhibitor DT-2 to block 8-Br-cGMP stimulation of SERT, we found that DT-2 treatment eliminated cGMP-dependent kinase activity in PKGI-immunoreactive extracts resolved by liquid chromatography. Similarly, treatment of SERT-transfected HeLa cells with small interfering RNAs targeting endogenous PKGI eliminated 8-Br-cGMP-induced regulation of SERT activity. Co-immunoprecipitation studies show that, in transporter/kinase co-transfected cells, PKGIα specifically associates with hSERT.</p> <p>Conclusion</p> <p>Our findings provide evidence of a physical and compartmentalized association between SERT and PKGIα that supports rapid, 8-Br-cGMP-induced regulation of SERT. We discuss a model wherein SERT-associated PKGIα supports sequentially the mobilization of intracellular transporter-containing vesicles, leading to enhanced surface expression, and the production of catalytic-modulatory SERT phosphorylation, leading to a maximal enhancement of 5-HT clearance capacity.</p

Practicing food anxiety: Making Australian mothers responsible for their families’ dietary decisions

Concerns about the relationship between diet, weight, and health find widespread expression in the media and are accompanied by significant individual anxiety and responsibilization. However, these pertain especially to mothers, who undertake the bulk of domestic labor involved in managing their families’ health and wellbeing. This article employs the concept of anxiety as social practice to explore the process whereby mothers are made accountable for their families’ dietary decisions. Drawing on data from an Australian study that explored the impact of discourses of childhood obesity prevention on mothers, the article argues that mothers’ engagements with this value-laden discourse are complex and ambiguous, involving varying degrees of self-ascribed responsibility and blame for children's weight and diets. We conclude by drawing attention to the value of viewing food anxiety as social practice, in highlighting issues that are largely invisible in both official discourses and scholarly accounts of childhood obesity prevention

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose