Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort.

BACKGROUND: Several studies have reported enlarged amygdala and smaller hippocampus volumes in children and adolescents exposed to maternal depression. It is unclear whether similar volumetric differences are detectable in the infants' first weeks of life, following exposure in utero. We investigated subcortical volumes in 2-to-6 week old infants exposed to antenatal maternal depression (AMD) from a South African birth cohort. METHODS: AMD was measured with the Beck Depression Inventory 2nd edition (BDI-II) at 28-32 weeks gestation. T2-weighted structural images were acquired during natural sleep on a 3T Siemens Allegra scanner. Subcortical regions were segmented based on the University of North Carolina neonatal brain atlas. Volumetric estimates were compared between AMD-exposed (BDI-II ⩾ 20) and unexposed (BDI-II < 14) infants, adjusted for age, sex and total intracranial volume using analysis of covariance. RESULTS: Larger volumes were observed in AMD-exposed (N = 49) compared to unexposed infants (N = 75) for the right amygdala (1.93% difference, p = 0.039) and bilateral caudate nucleus (left: 5.79% difference, p = 0.001; right: 6.09% difference, p < 0.001). A significant AMD-by-sex interaction was found for the hippocampus (left: F(1,118) = 4.80, p = 0.030; right: F(1,118) = 5.16, p = 0.025), reflecting greater volume in AMD-exposed females (left: 5.09% difference, p = 0.001, right: 3.54% difference, p = 0.010), but not males. CONCLUSIONS: Volumetric differences in subcortical regions can be detected in AMD-exposed infants soon after birth, suggesting structural changes may occur in utero. Female infants might exhibit volumetric changes that are not observed in male infants. The potential mechanisms underlying these early volumetric differences, and their significance for long-term child mental health, require further investigation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Record-setting algal bloom in Lake Erie caused by agricultural and meteorological trends consistent with expected future conditions

In 2011, Lake Erie experienced the largest harmful algal bloom in its recorded history, with a peak intensity over three times greater than any previously observed bloom. Here we show that long-term trends in agricultural practices are consistent with increasing phosphorus loading to the western basin of the lake, and that these trends, coupled with meteorological conditions in spring 2011, produced record-breaking nutrient loads. An extended period of weak lake circulation then led to abnormally long residence times that incubated the bloom, and warm and quiescent conditions after bloom onset allowed algae to remain near the top of the water column and prevented flushing of nutrients from the system. We further find that all of these factors are consistent with expected future conditions. If a scientifically guided management plan to mitigate these impacts is not implemented, we can therefore expect this bloom to be a harbinger of future blooms in Lake Erie.close1

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc