Glucocorticoids and Stress-Induced Changes in the Expression of PERIOD1 in the Rat Forebrain

The secretion of glucocorticoids in mammals is under circadian control, but glucocorticoids themselves are also implicated in modulating circadian clock gene expression. We have shown that the expression of the circadian clock protein PER1 in the forebrain is modulated by stress, and that this effect is associated with changes in plasma corticosterone levels, suggesting a possible role for glucocorticoids in the mediation of stress-induced changes in the expression of PER1 in the brain. To study this, we assessed the effects of adrenalectomy and of pretreatment with the glucocorticoid receptor antagonist, mifepristone, on the expression of PER1 in select limbic and hypothalamic regions following acute exposure to a neurogenic stressor, restraint, or a systemic stressor, 2-Deoxy-D-glucose (2DG) in rats. Acute restraint suppressed PER1 expression in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and the central nucleus of the amygdala (CEAl), whereas 2DG increased PER1 in both regions. Both stressors increased PER1 expression in the paraventricular (PVN) and dorsomedial (DMH) nuclei of the hypothalamus, and the piriform cortex (Pi). Adrenalectomy and pretreatment with mifepristone reversed the effects of both stressors on PER1 expression in the BNSTov and CEAl, and blocked their effects in the DMH. In contrast, both treatments enhanced the effects of restraint and 2DG on PER1 levels in the PVN. Stress-induced PER1 expression in the Pi was unaffected by either treatment. PER1 expression in the suprachiasmatic nucleus, the master circadian clock, was not altered by either exposure to stress or by the glucocorticoid manipulations. Together, the results demonstrate a key role for glucocorticoid signaling in stress-induced changes in PER1 expression in the brain

Neurological, Cognitive, and Psychological Findings Among Survivors of Ebola Virus Disease From the 1995 Ebola Outbreak in Kikwit, Democratic Republic of Congo: A Cross-sectional Study.

BackgroundClinical sequelae of Ebola virus disease (EVD) have not been described more than 3 years postoutbreak. We examined survivors and close contacts from the 1995 Ebola outbreak in Kikwit, Democratic Republic of Congo (DRC), and determined prevalence of abnormal neurological, cognitive, and psychological findings and their association with EVD survivorship.MethodsFrom August to September 2017, we conducted a cross-sectional study in Kikwit, DRC. Over 2 decades after the EVD outbreak, we recruited EVD survivors and close contacts from the outbreak to undergo physical examination and culturally adapted versions of the Folstein mini-mental status exam (MMSE) and Goldberg anxiety and depression scale (GADS). We estimated the strength of relationships between EVD survivorship and health outcomes using linear regression models by comparing survivors versus close contacts, adjusting for age, sex, educational level, marital status, and healthcare worker status.ResultsWe enrolled 20 EVD survivors and 187 close contacts. Among the 20 EVD survivors, 4 (20%) reported at least 1 abnormal neurological symptom, and 3 (15%) had an abnormal neurological examination. Among the 187 close contacts, 14 (11%) reported at least 1 abnormal neurologic symptom, and 9 (5%) had an abnormal neurological examination. EVD survivors had lower mean MMSE and higher mean GADS scores as compared to close contacts (MMSE: adjusted coefficient: -1.85; 95% confidence interval [CI]: -3.63, -0.07; GADS: adjusted coefficient: 3.91; 95% CI: 1.76, 6.04).ConclusionsEVD survivors can have lower cognitive scores and more symptoms of depression and anxiety than close contacts more than 2 decades after Ebola virus outbreaks

Building referral mechanisms for neonatal care in humanitarian emergency settings: A systematic review

AIM: During humanitarian emergencies, women and children are particularly vulnerable to health complications and neonatal mortality rates have been shown to rise. Additionally, health cluster partners face challenges in coordinating referrals, both between communities and camps to health facilities and across different levels of health facilities. The purpose of this review was to identify the primary referral needs of neonates during humanitarian emergencies, current gaps and barriers, and effective mechanisms for overcoming these barriers. METHODS: A systematic review was performed using four electronic databases (CINAHL, EMBASE, Medline, and Scopus) between June and August 2019 (PROSPERO registration number CRD42019127705). Title, abstract, and full text screening were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The target population was neonates born during humanitarian emergencies. Studies from high-income countries and prior to 1991 were excluded. The STROBE checklist was used to assess for risk of bias. RESULTS: A total of 11 articles were included in the analysis; these were mainly cross-sectional, field-based studies. The primary needs identified were referrals from homes to health facilities before and during labour, and inter-facility referrals after labour to more specialised services. Some of the main barriers included a lack of roads and infrastructure for transport, staff shortages-especially among more specialised services, and a lack of knowledge among patients for self-referral. Mechanisms for addressing these needs and gaps included providing training for community healthcare workers (CHWs) or traditional birth attendants to identify and address antenatal and post-natal complications; education programmes for pregnant women during the antenatal period; and establishing ambulance services in partnership with local Non-Governmental Organizations. CONCLUSION: This review benefited from a strong consensus among selected studies but was limited in the quality of data and types of data that were reported. Based on the above findings, the following recommendations were compiled: Focus on local capacity-building programmes to address programmes acutely. Recruit CHWs to raise awareness of neonatal complications among pregnant women. Upskill CHWs to provide timely, appropriate and quality care during humanitarian emergencies

Impaired perception of facial motion in autism spectrum disorder

Copyright: © 2014 O’Brien et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Facial motion is a special type of biological motion that transmits cues for socio-emotional communication and enables the discrimination of properties such as gender and identity. We used animated average faces to examine the ability of adults with autism spectrum disorders (ASD) to perceive facial motion. Participants completed increasingly difficult tasks involving the discrimination of (1) sequences of facial motion, (2) the identity of individuals based on their facial motion and (3) the gender of individuals. Stimuli were presented in both upright and upside-down orientations to test for the difference in inversion effects often found when comparing ASD with controls in face perception. The ASD group’s performance was impaired relative to the control group in all three tasks and unlike the control group, the individuals with ASD failed to show an inversion effect. These results point to a deficit in facial biological motion processing in people with autism, which we suggest is linked to deficits in lower level motion processing we have previously reported

Stress-Induced Changes in the Expression of the Clock Protein PERIOD1 in the Rat Limbic Forebrain and Hypothalamus: Role of Stress Type, Time of Day, and Predictability

Stressful events can disrupt circadian rhythms in mammals but mechanisms underlying this disruption remain largely unknown. One hypothesis is that stress alters circadian protein expression in the forebrain, leading to functional dysregulation of the brain circadian network and consequent disruption of circadian physiological and behavioral rhythms. Here we characterized the effects of several different stressors on the expression of the core clock protein, PER1 and the activity marker, FOS in select forebrain and hypothalamic nuclei in rats. We found that acute exposure to processive stressors, restraint and forced swim, elevated PER1 and FOS expression in the paraventricular and dorsomedial hypothalamic nuclei and piriform cortex but suppressed PER1 and FOS levels exclusively in the central nucleus of the amygdala (CEAl) and oval nucleus of the bed nucleus of the stria terminalis (BNSTov). Conversely, systemic stressors, interleukin-1β and 2-Deoxy-D-glucose, increased PER1 and FOS levels in all regions studied, including the CEAl and BNSTov. PER1 levels in the suprachiasmatic nucleus (SCN), the master pacemaker, were unaffected by any of the stress manipulations. The effect of stress on PER1 and FOS was modulated by time of day and, in the case of daily restraint, by predictability. These results demonstrate that the expression of PER1 in the forebrain is modulated by stress, consistent with the hypothesis that PER1 serves as a link between stress and the brain circadian network. Furthermore, the results show that the mechanisms that control PER1 and FOS expression in CEAl and BNSTov are uniquely sensitive to differences in the type of stressor. Finally, the finding that the effect of stress on PER1 parallels its effect on FOS supports the idea that Per1 functions as an immediate-early gene. Our observations point to a novel role for PER1 as a key player in the interface between stress and circadian rhythms

Antivenom Treatment Is Associated with Fewer Patients using Opioids after Copperhead Envenomation

Introduction Copperhead envenomation causes local tissue destruction, leading people to seek treatment for the pain and swelling. First-line treatment for the pain is opioid medications. There is rising concern that an initial opioid prescription from the emergency department (ED) can lead to long-term addiction. This analysis sought to determine whether use of Fab antivenom (FabAV) for copperhead envenomation affected opioid use. Methods We performed a secondary analysis using data from a randomized clinical trial designed to determine the effect of FabAV on limb injury recovery following mild to moderate copperhead envenomation. Opioid use was a defined secondary outcome in the parent trial. Patients were contacted after discharge, and data were obtained regarding medications used for pain and the patients’ functional status. This analysis describes the proportion of patients in each treatment group reporting opioid use at each time point. It also assesses the interaction between functional status and use of opioids. Results We enrolled 74 patients in the parent trial (45 received FabAV, 29 placebo), of whom 72 were included in this secondary analysis. Thirty-five reported use of any opioids after hospital discharge. A smaller proportion of patients treated with FabAV reported opioid use: 40.9% vs 60.7% of those in the placebo group. The proportion of patients using opioids remained smaller in the FabAV group at each follow-up time point. Controlling for confounders and interactions between variables, the model estimated that the odds ratio of using opioids after hospital discharge among those who received placebo was 5.67 times that of those who received FabAV. Patients who reported higher baseline pain, those with moderate as opposed to mild envenomation, and females were more likely to report opioid use at follow-up. Patients with ongoing limitations to functional status had an increased probability of opioid use, with a stronger association over time. Opioid use corresponded with the trial’s predefined criteria for full recovery, with only two patients reporting opioid use in the 24 hours prior to achieving full limb recovery and no patients in either group reporting opioid use after full limb recovery. Conclusion In this study population, the proportion of patients using opioids for pain related to envenomation was smaller in the FabAV treatment group at all follow-up time points

Refugees, healthcare and crises: informal Syrian health workers in Lebanon

In Syria, seven years of conflict has been catastrophic. Thousands of qualified doctors and health workers have left since 2011. In neighbouring countries, informal employment among displaced Syrian health workers is broadly acknowledged. But the scale, scope and nature are poorly documented. This working paper details both the scale and the challenges Syrian healthcare workers face in Lebanon. It explores strategies Syrian health workers use to help cope with barriers such as formal labour market entry, the threat of deportation, ethical challenges in practice, and discrimination. There is an urgent need to address legal barriers to registration to practise for Syrian healthcare workers. Key further research includes mapping health worker numbers, specialties and geographical distribution to support workforce planning, and research on current and potential training and development initiatives to further support Syrian health workers

Judging the Intensity of Emotional Expression in Faces: the Effects of Colored Tints on Individuals With Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) often show atypical processing of facial expressions, which may result from visual stress. In the current study, children with ASD and matched controls judged which member of a pair of faces displayed the more intense emotion. Both faces showed anger, disgust, fear, happiness, sadness or surprise but to different degrees. Faces were presented on a monitor that was tinted either gray or with a color previously selected by the participant individually as improving the clarity of text. Judgments of emotional intensity improved significantly with the addition of the preferred colored tint in the ASD group but not in controls, a result consistent with a link between visual stress and impairments in processing facial expressions in individuals with ASD. Autism Res 2016, 9: 450-459. © 2015 International Society for Autism Research, Wiley Periodicals, Inc

Empathy and emotion recognition in people with autism, first-degree relatives, and controls

Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed

Petrogenesis of rhyolite-trachyte-basalt composite ignimbrite P1, Gran Canaria, Canary Islands

The 14 Ma caldera-forming composite ignimbrite P1 on Gran Canaria (Canary Islands) represents the first voluminous eruption of highly differentiated magmas on top of the basaltic Miocene shield volcano. Compositional zonation of the ignimbrite is the result of vertically changing proportions of four component magmas, which were intensely mixed during eruption: (1) Crystal-poor to highly phyric rhyolite (∼10 km3), (2) sodic trachyandesite through mafic to evolved trachyte (∼6 km3), (3) Na-poor trachyandesite (<1 km3), and (4) basalt zoned from 5.2 to 4.3 wt % MgO (∼26 km3). P1 basalt is composed of two compositionally zoned magma batches, B2 basalt and B3 basalt. B3 basalt is derived from a mantle source depleted in incompatible trace elements compared to the shield basalt source. Basaltic magmas were stored in a reservoir probably underplating the crust, in which zoned B2 basaltic magma formed by mixing of “enriched” (shield) and “depleted” (B3) mafic melts and subsequent crystal fractionation. Evolved magmas formed in a shallow crustal chamber, whereas intermediate magmas formed at both levels. Abundant pyroxenitic to gabbroid cumulates in P1 support crystal fractionation as the major differentiation process. On the basis of major and trace element modeling, we infer two contemporaneous fractional crystallization series: series I from “enriched” shield basalt through Na-poor trachyandesite to rhyolite, and series II from “depleted” P1 basalt through sodic trachyandesite to trachyte. Series II rocks were significantly modified by selective contamination involving feldspar (Na, K, Ba, Eu, Sr), zircon (Zr) and apatite (P, Y, rare earth elements) components; apatite contamination also affected series I Na-poor trachyandesite. Substantial sodium introduction into sodic trachyandesite is the main reason for the different major element evolution of the two series, whereas their different parentage is mainly reflected in the high field strength trace elements. Selective element contamination involved not only rapidly but also slowly diffusing elements as well as different saturation conditions. Contamination processes thus variably involved differential diffusion, partial dissolution of minerals, partial melt migration, and trace mineral incorporation. Magma mixing between trachyte and rhyolite during their simultaneous crystallization in the P1 magma chamber is documented by mutual mineral inclusions but had little effect on the compositional evolution of both magmas. Fe-Ti oxide thermometry yields magmatic temperatures of around 850°C for crystal-poor through crystal-rich rhyolite, ∼815°C for trachyte and ∼850°–900°C for the trachyandesitic magmas. High 1160°C for the basalt magma suggest its intrusion into the P1 magma chamber only shortly before eruption. The lower temperature for trachyte compared to rhyolite and the strong crustal contamination of trachyte and sodic trachyandesite support their residence along the walls of the vertically and laterally zoned P1 magma chamber. The complex magmatic evolution of P1 reflects the transient state of Gran Canaria's mantle source composition and magma plumbing system during the change from basaltic to silicic volcanism. Our results for P1 characterize processes operating during this important transition, which also occurs on other volcanic ocean islands