Differential Expression of Sex-Steroid Receptors in the Choroid Aligns With Central Serous Chorioretinopathy Sex Prevalence Across Different Ages.

Purpose: The purpose of this study was to investigate the presence of sex-steroid receptors in human choroidal tissue across different ages and sex, aiming to better understand the pronounced sex difference in central serous chorioretinopathy (CSC) occurrence. Methods: Paraffin-embedded enucleated eyes of 14 premenopausal women, 15 postmenopausal women, 10 young men (<45 years), and 10 older men (>60 years) were used. A clinically certified immunostaining was performed to detect the presence of the androgen receptor (AR), progesterone receptor (PR; isoform A and B), and estrogen receptor (ERα). The stained slides were scored in a blinded manner for positive endothelial cells and stromal cells in consecutive sections of the same choroidal region. Results: Our analysis revealed the presence of AR, PR, and ERα in endothelial cells and stromal cells of choroidal tissue. The mean proportion of AR-positive endothelial cells was higher in young men (46% ± 0.15) compared to aged-matched women (29% ± 0.12; P < 0.05, 95% confidence interval [CI]). Premenopausal women showed markedly lower mean proportion of ERα (5% ± 0.02) and PR-positive endothelial cells (2% ± 0.01) compared to postmenopausal women (15% ± 0.07 and 19% ± 0.13; both P < 0.05, 95% CI), young men (13% ± 0.04 and 21% ± 0.10; both P < 0.05, 95% CI), and older men (18% ± 0.09 and 27% ± 0.14; both P < 0.05, 95% CI). Mean PR-positive stromal cells were also less present in premenopausal women (12% ± 0.07) than in other groups. Conclusions: The number of sex-steroid receptors in the choroidal tissue differs between men and women across different ages, which aligns with the prevalence patterns of CSC in men and postmenopausal women.

Process evaluation of the implementation of the assessment of burden of chronic conditions tool in Dutch primary care - lessons from a qualitative implementation study.

BACKGROUND: The Assessment of Burden of Chronic Conditions (ABCC-)tool is developed to facilitate a personalized approach to care in the patient-healthcare provider (HCP) conversation based on shared decision-making and individualized care plans. An effectiveness study highlighted its effect on the perceived quality of care and patient activation. Successful implementation of novel interventions necessitates an understanding of the user's actual application, user experiences and an evaluation of implementation outcomes. This study aims to evaluate the implementation of the ABCC-tool by HCPs in Dutch primary care. METHODS: This study is the process evaluation of a larger type 1 effectiveness-implementation hybrid trial. Semi-structured interviews with HCPs, who were interventionists in the hybrid trial, were held at three and twelve months after they started using the ABCC-tool. The Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) framework was used to evaluate implementation outcomes. The Implementation domain was further strengthened with an evaluation of implementation fidelity using Carroll's framework. Inductive coding and thematic analysis were applied to identify relevant participant experiences and implementation outcomes within the RE-AIM framework. RESULTS: Seventeen HCPs (1 general practitioner, 16 practice nurses) participated in the study, representing 39% of potentially eligible participants. Most HCPs applied the tool after finishing their own routines instead of how it is intended to be used, namely from the beginning of the consultation. HCPs reached 2-6 patients. The ABCC-tool was initially adopted, but twelve HCPs stopped using the tool due to COVID-19 related cancellation of consultations. High fidelity was found for applying the questionnaire and visualization. Low fidelity was present for applying shared decision-making, formulating care goals and monitoring progress. HCPs indicated that maintaning the ABCC-tool depended on accompanying training and implementation support. CONCLUSIONS: HCPs applied the ABCC-tool critically different from intended, potentially diminishing its benefits and ease of use. This evaluation stresses the need for a tailored implementation plan that includes more detailed training and guidance on how and when to use the ABCC-tool.

Low levels of Vitamin D during pregnancy associated with gestational diabetes mellitus and low birth weight: results from the MAASTHI birth cohort.

Introduction: India has a high prevalence of Vitamin D insufficiency among women of childbearing age. In this study, we aimed to evaluate the potential relationship between Vitamin D deficiency and gestational diabetes mellitus (GDM) and low birth weight (LBW) of newborns in the "Maternal antecedents of adiposity and studying the transgenerational role of hyperglycaemia and insulin" (MAASTHI) birth cohort. Methods: A prospective cohort study involving 230 participants was conducted in public hospitals located in urban Bengaluru, India. Healthy pregnant women who visited these hospitals for antenatal care (ANC) and who were between 14 and 36 weeks of gestational age were recruited after obtaining their informed consent. An oral glucose tolerance test (OGTT) was administered between 24 and 36 weeks of pregnancy and blood samples were preserved at -80°C for Vitamin D analysis. Follow-up at birth included recording the child's birth weight. Results: We found that 178 (77.4%) of the study participants were vitamin D deficient, 44 (19.1%) were diagnosed with GDM, and 64 (27.8%) gave birth to LBW babies. Women in the lowest quartile of serum Vitamin D levels had three times higher odds of developing GDM than women in the higher quartiles [OR = 3.22 (95% CI: 1.03, 10.07), p = 0.04] after adjusting for age, parity, socioeconomic status, season, and adiposity. For every one-unit increase in Vitamin D levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) decreased by nearly 18%. Furthermore, causal mediation analysis showed that a decrease in one unit of Vitamin D is associated with a decrease of 0.015 units of fasting blood sugar (FBS) and 0.019 units of postprandial blood sugar (PPBS) as it flows through the mediator variable insulin resistance. Vitamin D-deficient women were twice at risk of giving birth to LBW babies (OR 2.04, 95% CI 0.99, 4.19, p = 0.05). Discussions: Low levels of Vitamin D during pregnancy are associated with a greater risk of pregnant women developing GDM and giving birth to LBW babies in urban Bengaluru.

Undesirable Levels of Practice Behaviours and Associated Knowledge amongst Community Health Workers in Rural South India Responsible for Type 2 Diabetes Screening and Management.

BACKGROUND: Type 2 diabetes (T2DM) poses an enormous global health care challenge, especially among rural communities. Healthcare in these areas can be inadequate and inaccessible due to socio-demographic barriers. To overcome this situation, many low- and middle-income countries are resorting to task shifting, using community health workers (CHWs) for diabetes management. However, its successful implementation depends on the practice behaviours and knowledge of these workers. OBJECTIVE: This cross-sectional study aimed to evaluate the proficiency of CHWs involved in diabetes screening and management in rural South India by identifying the existing practice behaviours and knowledge gaps. METHODS: Employing a customised questionnaire, developed through inputs from experts and government officials, we assessed practice behaviours and the corresponding knowledge base of 275 CHWs. Analytical methodologies consisted of descriptive statistics, logistic regression, and mosaic plots for comprehensive data interpretation. RESULTS: The study showcased significant deficiencies in both practice behaviours (97%) and knowledge (95%) with current mean levels ranging from 48 to 50%, respectively, among the participants. The identified areas of insufficiency were broadly representative of the core competencies required for effective diabetes management, encompassing diabetes diagnosis and referral, HbA1c testing, diabetes diet, diabetes type and self-management, microvascular complications and their screening, peripheral neuropathy management, and diabetes risk assessment. In several areas, correct practice behaviour was reported by a relatively large number of CHWs despite incorrect answers to the related knowledge questions such as referral to the health centres, self-management, and calculation of diabetes risk assessment. CONCLUSION: This study highlights widespread deficiencies (97% CHWs) in diabetes management practices and knowledge (95% CHWs). To overcome these deficiencies, a thorough needs assessments is vital for effective CHW training. Training of CHWs should not only identify prior knowledge and/or behaviour but also their interrelationship to help create a robust and flexible set of practice behaviours.

Three Prospective Case Studies Examining Mifepristone's Efficacy in Patients with Treatment-Resistant PTSD.

Despite the availability of various treatment approaches for patients with posttraumatic stress disorder (PTSD), some patients do not respond to these therapies, and novel treatment approaches are needed. This study investigated the efficacy of mifepristone, a glucocorticoid receptor antagonist, in treatment-resistant PTSD patients. Three patients with PTSD who were resistant to standard psychological and pharmacological treatments were prescribed mifepristone (600-1,200 mg/day) for 1 week. A baseline-controlled single-case design was used, involving a 2-week baseline phase (no intervention), a 1-week intervention phase (mifepristone), and a 2-week postintervention phase. The primary outcome measure, self-reported PTSD symptom severity (PCL-5), was assessed daily, with participants providing their own control condition. Two of the three patients experienced a significant reduction in PTSD symptom severity after the intervention phase and no longer met the diagnostic criteria for PTSD. These positive results were maintained during long-term follow-up. These findings support the potential effectiveness of mifepristone in the treatment of patients with treatment-resistant PTSD. However, our findings must be interpreted with caution, and further studies with larger sample sizes and more rigorous designs are necessary to confirm the promising results.

Corrigendum to "Association of high cortisol levels in pregnancy and altered fetal growth. Results from the MAASTHI, a prospective cohort study, Bengaluru" [The Lancet Regional Health - Southeast Asia 14 (2023) 100196].

[This corrects the article DOI: 10.1016/j.lansea.2023.100196.].

Effectiveness of the Assessment of Burden of Chronic Conditions (ABCC)-tool in patients with asthma, COPD, type 2 diabetes mellitus, and heart failure: A pragmatic clustered quasi-experimental study in the Netherlands.

BACKGROUND: The Assessment of Burden of Chronic Conditions (ABCC)-tool was developed to optimise chronic care. OBJECTIVES: This study aimed to assess the effectiveness of the ABCC-tool in patients with COPD, asthma, type 2 diabetes, and/or heart failure in primary care in the Netherlands. METHODS: The study had a pragmatic, clustered, two-armed, quasi-experimental design. The intervention group (41 general practices; 176 patients) used the ABCC-tool during routine consultations and the control group (14 general practices; 61 patients) received usual care. The primary outcome was a change in perceived quality of care (PACIC; Patient Assessment of Chronic Illness Care) after 18 months. Secondary outcomes included change in the PACIC after 6 and 12 months, and in quality of life (EQ-5D-5L; EuroQol-5D-5L), capability well-being (ICECAP-A; ICEpop CAPability measure for Adults), and patients' activation (PAM; Patient Activation Measure) after 6, 12, and 18 months for the total group and conditions separately. RESULTS: We observed a significant difference in the PACIC after 6, 12, and 18 months (18 months: 0.388 points; 95%CI: 0.089-0.687; p = 0.011) for the total group and after 6 and 12 months for type 2 diabetes. After 18 months, we observed a significant difference in the PAM for the total group but not at 6 and 12 months, and not for type 2 diabetes. All significant effects were in favour of the intervention group. No significant differences were found for the EQ-5D-5L and the ICECAP-A. CONCLUSION: Use of the ABCC-tool has a positive effect on perceived quality of care and patients' activation, which makes the tool ready for use in clinical practice. Healthcare providers (e.g. general practitioners and practice nurses) can use the tool to provide person-centred care.Trial registration number: ClinicalTrials.gov Registry (NCT04127383).

The Assessment of Burden of Chronic Conditions (ABCC)-tool aims to support disease management for one or multiple chronic condition(s), currently COPD, asthma, type 2 diabetes, and heart failure.Statistically significant differences in patients' perceived quality of care and patient activation were found between the group that used the ABCC-tool and the care-as-usual group. No effect was found on generic quality of life or capability well-being.Healthcare providers can use the ABCC-tool in primary care.

Glucocorticoid receptor antagonist CORT113176 attenuates motor and neuropathological symptoms of Huntington's disease in R6/2 mice.

Huntington's Disease (HD) is a progressive neurodegenerative disease caused by a mutation in the huntingtin gene. The mutation leads to a toxic gain of function of the mutant huntingtin (mHtt) protein resulting in cellular malfunction, aberrant huntingtin aggregation and eventually neuronal cell death. Patients with HD show impaired motor functions and cognitive decline. Elevated levels of glucocorticoids have been found in HD patients and in HD mouse models, and there is a positive correlation between increased glucocorticoid levels and the progression of HD. Therefore, antagonism of the glucocorticoid receptor (GR) may be an interesting strategy for the treatment of HD. In this study, we evaluated the efficacy of the selective GR antagonist CORT113176 in the commonly used R6/2 mouse model. In male mice, CORT113176 treatment significantly delayed the loss of grip strength, the development of hindlimb clasping, gait abnormalities, and the occurrence of epileptic seizures. CORT113176 treatment delayed loss of DARPP-32 immunoreactivity in the dorsolateral striatum. It also restored HD-related parameters including astrocyte markers in both the dorsolateral striatum and the hippocampus, and microglia markers in the hippocampus. This suggests that CORT113176 has both cell-type and brain region-specific effects. CORT113176 delayed the formation of mHtt aggregates in the striatum and the hippocampus. In female mice, we did not observe major effects of CORT113176 treatment on HD-related symptoms, with the exception of the anti-epileptic effects. We conclude that CORT113176 effectively delays several key symptoms related to the HD phenotype in male R6/2 mice and believe that GR antagonism may be a possible treatment option.

Recommendations for Improving Chronic Care in Times of a Pandemic Based on Patient Experiences.

OBJECTIVES: The COVID-19 pandemic had a profound and pervasive impact on the health of chronic care patients and disrupted care systems worldwide. Our research aimed to assess the impact of the pandemic on chronic care provision and provide recommendations for improving care provision, based on patient experiences. DESIGN: Qualitative semi-structured interviews were held among patients with chronic obstructive pulmonary disease (COPD) or heart failure. SETTING AND PARTICIPANTS: Using stratified sampling, 23 patients with COPD, heart failure, or both were recruited to participate in semi-structured interviews. In the summer of 2021, online interviews were conducted. METHODS: An iterative process was adopted to analyze the data. Going back and forth through the data and our analytical structure, we first coded the data, and subsequently developed categories, themes, and aggregate dimensions. The data were synthesized in a data structure and a data table, which were analyzed using an interpretative approach. RESULTS: We found 3 dimensions through which care might be improved: (1) proactive and adaptive health care organization and use of innovative technologies, (2) assistance in maintaining patient resilience and coping strategies, and (3) health care built on outreaching and person-centered care enabling identification of individual patient needs. Experiences of impaired accessibility to care, altered and unmet care demands and patient needs, and the negative impact of national containment strategies on patient resilience support the need for improvement in these dimensions. CONCLUSIONS AND IMPLICATIONS: The in-depth insight gained on the impact of the pandemic on chronic care provision was used to propose recommendations for improving care, supported by not only the what and how but also the why developments require additional efforts made by policymakers and change agents, augmented by structural use and development of innovations. Health care organizations should be enabled to rapidly respond to changing internal and external environments, develop and implement innovations, and match care to patient needs.

Antibiotics Versus Placebo for Acute Bacterial Conjunctivitis: Findings From a Cochrane Systematic Review.

PURPOSE: To summarize key findings from a Cochrane review of the benefits and safety of antibiotic therapy compared with placebo (or vehicle) for acute bacterial conjunctivitis. DESIGN: Systematic review and meta-analysis. METHODS: We included placebo-controlled randomized controlled trials (RCTs) that compared topical antibiotics with placebo. We followed Cochrane methods for trial selection, data extraction, risk of bias assessment, and evidence synthesis. RESULTS: Twenty-one RCTs involving 8805 participants with acute bacterial conjunctivitis were included. Fifteen (71%) RCTs examined fluoroquinolone (FQ) drops, 3 tested macrolides, alone or in combination with steroids, and another 3 compared other non-FQ antibiotics. Intention-to-treat estimates suggested that compared with placebo, antibiotics may increase clinical recovery by 26% (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.09-1.46) at the end of therapy (5 RCTs, 1474 participants). Modified intention-to-treat estimates, in which only participants with laboratory-confirmed bacterial conjunctivitis were analyzed, indicated that antibiotics were associated with 53% higher likelihood of microbiological cure as compared with placebo (RR: 1.53; 95% CI: 1.34-1.74; 10 RCTs, 2827 participants). Non-FQs (RR: 4.05; 95% CI: 1.36-12.00), but not FQs (RR: 0.70; 95% CI: 0.54-0.90), were likely to increase treatment-associated ocular complications such as eye pain, discomfort, and allergic reactions; the certainty of level of evidence was very low. CONCLUSIONS: Moderate level certainty of evidence suggested that antibiotics may increase the likelihood of clinical recovery and microbiological clearance compared with placebo. Very low-level certainty of evidence suggested that antibiotics may be associated with potential harm in patients with acute bacterial conjunctivitis, but the potential risk of bias from study design, inconsistency in outcome measurement, and reporting limit the evidence to very low certainty.

Harnessing PROTAC technology to combat stress hormone receptor activation.

Counteracting the overactivation of glucocorticoid receptors (GR) is an important therapeutic goal in stress-related psychiatry and beyond. The only clinically approved GR antagonist lacks selectivity and induces unwanted side effects. To complement existing tools of small-molecule-based inhibitors, we present a highly potent, catalytically-driven GR degrader, KH-103, based on proteolysis-targeting chimera technology. This selective degrader enables immediate and reversible GR depletion that is independent of genetic manipulation and circumvents transcriptional adaptations to inhibition. KH-103 achieves passive inhibition, preventing agonistic induction of gene expression, and significantly averts the GR's genomic effects compared to two currently available inhibitors. Application in primary-neuron cultures revealed the dependency of a glucocorticoid-induced increase in spontaneous calcium activity on GR. Finally, we present a proof of concept for application in vivo. KH-103 opens opportunities for a more lucid interpretation of GR functions with translational potential.

Neuropsychiatric adverse effects of synthetic glucocorticoids: A systematic review and meta-analysis.

BACKGROUND: Synthetic glucocorticoids are widely used among patients suffering from a wide range of diseases. Glucocorticoids are very efficacious, but can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids. METHODS: Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and non-users were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model. RESULTS: We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95%CI 14%-33%), 11% for mania (95%CI 2%-46%), 8% for anxiety (95%CI 2%-25%), 16% for delirium (95%CI 6%-36%), and 52% for behavioural changes (95%CI 42%-61%). Questionnaire scores for depression (SMD of 0.80 (95%CI 0.35-1.26)), and mania (0.78 (95%CI 0.14-1.42)) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use. CONCLUSIONS: The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.

The importance of the circadian trough in glucocorticoid signaling: a variation on B-flat.

Glucocorticoid hormones are essential for health, but overexposure may lead to many detrimental effects, including metabolic, psychiatric, and bone disease. These effects may not only be due to increased overall exposure to glucocorticoids, but also to elevated hormone levels at the time of the physiological circadian trough of glucocorticoid levels. The late Mary Dallman developed a model that allows the differentiation between the effects of overall 24-hour glucocorticoid overexposure and the effects of a lack of circadian rhythmicity. For this, she continuously treated rats with a low dose of corticosterone (or "B"), which leads to a constant hormone level, without 24-hour overexposure using subcutaneously implanted pellets. The data from this "B-flat" model suggest that even modest elevations of glucocorticoid signaling during the time of the normal circadian trough of hormone secretion are a substantial contributor to the negative effects of glucocorticoids on health.

Feeding styles and adiposity in children of 6 months- 5 years of age: Protocol for a systematic review and meta- analysis.

Obesity in children is a major public health concern due to the increased risk of developing adverse health outcomes in their future, and disability in adulthood. The existing systematic reviews on the topic are limited in scope, focusing solely on high-income countries and children aged 4-12 years. Hence, we propose to conduct a systematic review and meta-analysis to understand, how exposure to authoritative feeding style versus authoritarian, indulgent, uninvolved compare in terms of its association with adiposity in children aged 6 months to 5 years. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines were followed for ensuring the completeness of the protocol. Case-control and cohort studies will be included. Searches will be done using electronic databases viz. PubMed, Ovid EMBASE, PsycINFO and Web of Science. Grey literature will be searched using OpenGrey and Grey Literature Report. We will only include quantitative studies using the developed search strategy. For categorical outcomes, relative risks, odds ratios, and hazard ratios with confidence intervals and for continuous outcomes mean difference with confidence intervals will be used. Risk of Bias In Non-randomized Studies- of Exposure (ROBINS-E) will be used for the evaluation of risk of bias in the individual observational studies. Considering the inherent variability in the observational studies, random effects meta-analysis will also be conducted. If between-study heterogeneity exists, a subgroup analysis based on low and middle-income countries vs. high income countries will be conducted. If the data is not suitable for combining quantitatively, a narrative synthesis will be undertaken. We propose to identify publication bias by using contour-enhanced funnel plots and "trim and fill" method. Outcome reporting bias will be ascertained by comparing the outcomes published in the protocol and the published report. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to understand the confidence we can have on the effect estimates. Registration: This protocol has been registered in International Prospective Register of Systematic Reviews (PROSPERO) on 13 March 2023 with registration number CRD42023356014.

Comparison of two corticosteroid regimens on brain volumetrics in patients with Duchenne muscular dystrophy.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI). METHODS: In a cross-sectional, two-center study, T1-weighted MRI scans were obtained from three age-matched groups (9-18 years): DMD patients treated daily with deflazacort (DMDd, n = 20, scan site: Leuven), DMD patients treated intermittently with prednisone (DMDi, n = 20, scan site: Leiden), and healthy controls (n = 40, both scan sites). FSL was used to perform voxel-based morphometry analyses and to calculate intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volumes. A MANCOVA was employed to compare global volumetrics between groups, with site as covariate. RESULTS: Both patient groups displayed regional differences in gray matter volumes compared to the control group. The DMDd group showed a wider extent of brain regions affected and a greater difference overall. This was substantiated by the global volume quantification: the DMDd group, but not the DMDi group, showed significant differences in gray matter, white matter, and cerebrospinal fluid volumes compared to the control group, after correction for intracranial volume. INTERPRETATION: Volumetric differences in the brain are considered part of the DMD phenotype. This study suggests an additional impact of corticosteroid treatment showing a contrast between pronounced alterations seen in patients receiving daily corticosteroid treatment and more subtle differences in those treated intermittently.

Temporal associations between salivary cortisol and emotions in clinically depressed individuals and matched controls: A dynamic time warp analysis.

Depression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but knowledge on the temporal interplay between cortisol and depressive symptoms is scarce. We aimed to analyze the temporal connectivity between salivary cortisol and momentary affective states in depressed individuals and controls. Thirty pair-matched depressed and non-depressed participants completed questionnaires on momentary positive (PA) and negative (NA) affect and collected saliva three times a day for 30 days. The association between cortisol and affect was analyzed by dynamic time warp (DTW) analyses. These analyses involved lag-1 backward to lag-1 forward undirected analyses and lag-0 and lag-1 forward directed analyses. Large inter- and intra-individual variability in the networks were found. At the group level, with undirected analysis PA and NA were connected in the networks in depressed individuals and in controls. Directed analyses indicated that increases in cortisol preceded specific NA items in controls, but tended to follow upon specific affect items increase in depressed individuals. To conclude, at group level, changes in cortisol levels in individuals diagnosed with a depression may be a result of changes in affect, rather than a cause.

Effects of School-Based Health-Promoting Activities on Children's Health: A Pragmatic Real-World Study.

More insight into the health effects of scaled-up school-based interventions in real-world settings is vital to sustainably integrate health in all schools. This study investigated the effectiveness of the scaled-up Healthy Primary School of the Future (HPSF) initiative in real-world school contexts on children's health (behaviours). From 2019 to 2022, eleven Dutch primary schools implemented HPSF-related activities. In 315 children from study years four to six (aged 7-11 years) from these schools, anthropometric measurements were performed, and questionnaires assessing the children's dietary behaviours and physical activity were administered. COVID-19 greatly limited the implementation of HPSF-related activities. Therefore, the results were compared between schools categorised as medium implementers and schools categorised as low implementers. After correction for baseline, waist circumference in the medium implementer group was significantly higher at one-year follow-up (B = 1.089, p = 0.003) and two-year follow-up (B = 1.665, p < 0.001) compared with waist circumference in the low implementer group. No significant effects were observed for other outcomes. This study showed hardly any effects of the scaled-up HPSF initiative, mainly due to the limited implementation caused by COVID-19. More research investigating the real-world effectiveness of HPSF and comparable programmes is greatly encouraged to advance the field of school-based health promotion.

Glucocorticoid receptor modulator CORT125385 alleviates diet-induced hepatosteatosis in male and female mice.

Non-alcoholic fatty liver disease (NAFLD) is a common condition that can progress to the more severe conditions like non-alcoholic steatohepatitis (NASH) for which limited effective therapeutic options are available. In this study, we set out to evaluate the novel glucocorticoid receptor modulator CORT125385, an analogue of the previously studied miricorilant but without mineralocorticoid receptor binding activity. Male and female mice that received high-fat diet and fructose water were treated with either vehicle, CORT125385 or mifepristone. We found that CORT125385 significantly lowered hepatic triglyceride levels in male mice, and hepatic triglyceride and cholesterol levels in female mice. Mifepristone treatment had no effect in male mice, but significantly lowered hepatic triglyceride and cholesterol levels in female mice. In reporter assays in vitro, CORT125385 showed weak partial agonism on the progesterone receptor (PR) at high doses, as well as PR antagonism at a potency 1000-fold lower than mifepristone. In vivo, CORT125385 treatment did not influence PR-responsive gene expression in the oviduct, while mifepristone treatment strongly influenced these genes in the oviduct, thus excluding in vivo PR cross-reactivity of CORT125385 at a therapeutically active dose. We conclude that CORT125385 is a promising glucocorticoid receptor modulator that effectively reduces liver steatosis in male and female mice without affecting other steroid receptors at doses that lower hepatic lipid content.

Association of high cortisol levels in pregnancy and altered fetal growth. Results from the MAASTHI, a prospective cohort study, Bengaluru.

Background: The role of maternal stress levels on mothers' mental health and fetal growth has been previously studied. However, the evidence linking cortisol exposure during pregnancy to growth outcomes in infants is sparsely available from lower and middle-income countries. We aim to investigate the association of serum cortisol levels in pregnancy with infant birth outcomes and postpartum depressive symptoms in a public health facility in India. Methods: The current study is a part of the maternal antecedents of adiposity and studying the transgenerational role of hyperglycemia and insulin (MAASTHI) prospective cohort. We assessed the relationship between maternal exposure to serum cortisol and adverse neonatal outcomes and postpartum depressive symptoms. Serum cortisol levels in stored blood samples were measured in 230 pregnant women as a biomarker for stress during pregnancy. Pregnant women between 18 and 45 years of age were recruited for the study, presenting at ≥14 weeks of gestation and providing voluntary written informed consent. The Edinburgh Postnatal Depression Scale assessed postpartum depressive symptoms, and detailed infant anthropometric measurements were carried out at birth. Findings: We found that higher levels (>17.66 µg/L) are significantly associated with low birth weight (OR = 2.28; 95% CI 1.21-4.32) and lower weight for length (OR = 2.16; 95% CI 1.07-4.35). The odds of developing postpartum depressive symptoms in pregnant women with higher mean cortisol cut-off levels is 2.3-fold [OR: 2.33, 95% CI (1.17, 4.64)] compared than women with lower cortisol levels. No significant association was found between serum cortisol and infants' birth weight for gestational age, head circumference, the sum of skinfold thickness, and crown-rump length. Interpretation: Our results support the hypothesis that higher maternal cortisol levels may adversely impact birth weight, weight for length in newborns, and postpartum depressive symptoms in mothers. Funding: This study was supported by the India Alliance Senior Fellowship [Grant No. IA/CPHS/20/1/505278] awarded to Giridhara R. Babu.