Background Glucose management is challenging in patients who require nutritional support in hospital. We aimed to assess whether fully closed-loop insulin delivery would improve glycaemic control compared with conventional subcutaneous insulin therapy in inpatients receiving enteral or parenteral nutrition or both. Methods We did a two-centre (UK and Switzerland), open-label, randomised controlled trial in adult inpatients receiving enteral or parenteral nutrition (or both) who required subcutaneous insulin therapy. Patients recruited from non-critical care surgical and medical wards were randomly assigned (1:1) using a computer-generated minimisation schedule (stratified by type of nutritional support [parenteral nutrition on or off] and pre-study total daily insulin dose [<50 or ≥50 units]) to receive fully closed-loop insulin delivery with faster-acting insulin aspart (closed-loop group) or conventional subcutaneous insulin therapy (control group) given in accordance with local clinical practice. Continuous glucose monitoring in the control group was masked to patients, ward staff, and investigators. Patients were followed up for a maximum of 15 days or until hospital discharge. The primary endpoint was the proportion of time that sensor glucose concentration was in target range (5•6-10•0 mmol/L), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01774565.

No abstract

The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

No abstract

This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

Traditionally sex hormones have been associated with reproductive and developmental processes only. Since the 1950s we know that hormones can have organizational effects on the developing brain and initiate hormonal transition periods such as puberty. However, recent evidence shows that sex hormones additionally structure the brain during important hormonal transition periods across a woman’s life including short-term fluctuations during the menstrual cycle. However, a comprehensive review focusing on structural changes during all hormonal transition phases of women is still missing. Therefore, in this review structural changes across hormonal transition periods (i.e., puberty, menstrual cycle, oral contraceptive intake, pregnancy and menopause) were investigated in a structured way and correlations with sex hormones evaluated. Results show an overall reduction in grey matter and region-specific decreases in prefrontal, parietal and middle temporal areas during puberty. Across the menstrual cycle grey matter plasticity in the hippocampus, the amygdala as well as temporal and parietal regions were most consistently reported. Studies reporting on pre- and post-pregnancy measurements revealed volume reductions in midline structures as well as prefrontal and temporal cortices. During perimenopause, the decline in sex hormones was paralleled with a reduction in hippocampal and parietal cortex volume. Brain volume changes were significantly correlated with estradiol, testosterone and progesterone levels in some studies, but directionality remains inconclusive between studies. These results indicate that sex hormones play an important role in shaping women’s brain structure during different transition periods and are not restricted to specific developmental periods.

Women have a lifetime risk of major depression double that of men but only during their reproductive years. This sex difference has been attributed partially to activational effects of female sex steroids and also to the burdens of pregnancy, childbirth, and parenting. Men, in contrast, have a reproductive period difficult to delineate, and research on the mental health of men has rarely considered the effects of fatherhood. However, the couple goes through a number of potentially stressing events during the reproductive period, and both mothers and fathers are at risk of developing peripartum depression. This Review discusses the literature on maternal and paternal depression and the endocrine changes that may predispose a person to depression at this stage of life, with specific focus on the hypothalamus-pituitary axis, oxytocin, and testosterone levels in men. Important findings on sex differences in the neural correlates of maternal and paternal behavior have emerged, highlighting the relevance of the emotional brain in mothers and the sociocognitive brain in fathers and pointing toward the presence of a common parents' brain. Additionally, sex differences in neurogenesis and brain plasticity are described in relation to peripartum depression.

Pregnancy is accompanied by complex biological adaptations, including extreme hormonal fluctuations. Moreover, changes on the endocrine level are accompanied by changes in cerebral anatomy, such as reductions in brain or gray matter volume. Since declining brain and tissue volumes are characteristic for normal aging, the question arises of whether such pregnancy-induced anatomical effects are permanent or transient. To answer this question, we acquired high-resolution brain image data of 14 healthy women in their mid-twenties to late thirties at two time points: within 1-2 days of childbirth (early postpartum) and at 4-6 weeks after childbirth (late postpartum). At both time points, we estimated the brain ages for each woman using a well-validated machine learning approach based on pattern recognition. Ultimately, this algorithm - designed to identify anatomical correlates of age across the entire brain - reveals a single score for each individual: the BrainAGE index. Comparing the BrainAGE indices between both time points, female brains at late postpartum were estimated to be considerably younger than at early postpartum. On average, that difference was about five years (mean ± SD: 5.4 ± 2.4 years). These findings suggest a substantial restoration/rejuvenation effect after giving birth, which is evident already within the first couple of months.