Fetal brain 11β-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice

Stress or elevated glucocorticoids during sensitive windows of fetal development increase the risk of neuropsychiatric disorders in adult rodents and humans, a phenomenon known as glucocorticoid programming. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2), which catalyses rapid inactivation of glucocorticoids in the placenta, controls access of maternal glucocorticoids to the fetal compartment, placing it in a key position to modulate glucocorticoid programming of behavior. However, the importance of the high expression of 11β-HSD2 within the midgestational fetal brain is unknown. To examine this, a brain-specific knockout of 11β-HSD2 (HSD2BKO) was generated and compared to wild-type littermates. HSD2BKO have markedly diminished fetal brain 11β-HSD2, but intact fetal body and placental 11β-HSD2 and normal fetal and placental growth. Despite normal fetal plasma corticosterone, HSD2BKO exhibit elevated fetal brain corticosterone levels at midgestation. As adults, HSD2BKO show depressive-like behavior and have cognitive impairments. However, unlike complete feto-placental deficiency, HSD2BKO show no anxiety-like behavioral deficits. The clear mechanistic separation of the programmed components of depression and cognition from anxiety implies distinct mechanisms of pathogenesis, affording potential opportunities for stratified interventions

Factors associated with older patients' engagement in exercise after hospital discharge

Objectives To identify factors that are associated with older patients' engagement in exercise in the 6 months after hospital discharge. Design A prospective observational study using qualitative and quantitative evaluation. Setting Follow-up of hospital patients in their home setting after discharge from a metropolitan general hospital. Participants Participants (N=343) were older patients (mean age ± SD, 79.4±8.5y) discharged from medical, surgical, and rehabilitation wards and followed up for 6 months after discharge. Interventions Not applicable. Main Outcome Measures Self-perceived awareness and risk of falls measured at discharge with a survey that addressed elements of the Health Belief Model. Engagement and self-reported barriers to engagement in exercise measured at 6 months after discharge using a telephone survey. Results Six months after discharge, 305 participants remained in the study, of whom 109 (35.7%) were engaging in a structured exercise program. Multivariable logistic regression analysis demonstrated participants were more likely to be engaging in exercise if they perceived they were at risk of serious injury from a fall (odds ratio [OR] =.61; 95% confidence interval [CI], .48–.78; P<.001), if exercise was recommended by the hospital physiotherapist (OR=1.93; 95% CI, 1.03–3.59; P=.04), and if they lived with a partner (OR=1.97; 95% CI, 1.18–3.28; P=.009). Barriers to exercise identified by 168 participants (55%) included low self-efficacy, low motivation, medical problems such as pain, and impediments to program delivery. Conclusions Older patients have low levels of engagement in exercise after hospital discharge. Researchers should design exercise programs that address identified barriers and facilitators, and provide education to enhance motivation and self-efficacy to exercise in this population

Curbing adult student attrition: Evidence from a field experiment Curbing adult student attrition: Evidence from a field experiment* Curbing adult student attrition: Evidence from a field experiment *

Abstract Finding a job, especially in a recovering economy, is challenging and success is reliant upon effective job-search activity. Jobseekers Allowance (JSA) welfare benefit claimants in the United Kingdom have many competing options available to them in terms of how they direct their efforts in looking for work. Often it is hard to determine which is most productive. Unsurprisingly, Jobcentres -the organisations that support JSA claimants during their unemployment -themselves have very strong links to the labour market. For example, they are often invited to run recruitment events in direct partnership with large employers seeking to hire in bulk. At Bedford Jobcentre, we observe that, despite the relatively high likelihood of gaining work from attending such events, jobseeker attendance rates are still low and, instead, we can only assume that jobseekers may be taking part in less productive work search activities. This paper reports the results of a randomised control trial designed to test the effectiveness of mobile phone text messaging in compelling jobseekers in the Bedford area to attend such events. Tailored text messages are found to significantly increase the likelihood of attendance. We find text messages to be particularly effective when they evoke a sense of reciprocity in the recipient. Electronic version: Address for correspondence CMPO 2 Priory Road, Bristol BS8 1TX www.bristol.ac.uk/cmpo/ [email protected] Tel +4

OSIRIS-APEX: An OSIRIS-REx Extended Mission to Asteroid Apophis

The Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS-REx) spacecraft mission characterized and collected a sample from asteroid (101955) Bennu. After the OSIRIS-REx Sample Return Capsule released to Earth’s surface in 2023 September, the spacecraft diverted into a new orbit that encounters asteroid (99942) Apophis in 2029, enabling a second mission with the same unique capabilities: OSIRIS–Apophis Explorer (APEX). On 2029 April 13, the 340 m diameter Apophis will draw within ∼32,000 km of Earth’s surface, less than 1/10 the lunar distance. Apophis will be the largest object to approach Earth this closely in recorded history. This rare planetary encounter will alter Apophis’s orbit, will subject it to tidal forces that change its spin state, and may seismically disturb its surface. APEX will distantly observe Apophis during the Earth encounter and capture its evolution in real time, revealing the consequences of an asteroid undergoing tidal disturbance by a major planet. Beginning in 2029 July, the spacecraft’s instrument suite will begin providing high-resolution data of this “stony” asteroid—advancing knowledge of these objects and their connection to meteorites. Near the mission’s end, APEX will use its thrusters to excavate regolith, a technique demonstrated at Bennu. Observations before, during, and after excavation will provide insight into the subsurface and material properties of stony asteroids. Furthermore, Apophis’s material and structure have critical implications for planetary defense

Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial

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Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

International audienceAbstract Background Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO 2 ) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO 2 with patients’ outcome. Methods Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO 2  300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO 2 -AUC), for hyperoxemia was significantly associated with mortality ( p = 0.003). Conclusions In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration : clinicaltrials.gov NCT02908308 , Registered September 20, 2016