Subcallosal area 25: Its responsivity to the stress hormone cortisol and its opposing effects on appetitive motivation in marmosets.

Aberrant activity in caudal subcallosal anterior cingulate cortex (scACC) is implicated in depression and anxiety symptomatology, with its normalisation a putative biomarker of successful treatment response. The function of scACC in emotion processing and mental health is not fully understood despite its known influence on stress-mediated processes through its rich expression of mineralocorticoid and glucocorticoid receptors. Here we examine the causal interaction between area 25 within scACC (scACC-25) and the stress hormone, cortisol, in the context of anhedonia and anxiety-like behaviour. In addition, the overall role of scACC-25 in hedonic capacity and motivation is investigated under transient pharmacological inactivation and overactivation. The results suggest that a local increase of cortisol in scACC-25 shows a rapid induction of anticipatory anhedonia and increased responsiveness to uncertain threat. Separate inactivation and overactivation of scACC-25 increased and decreased motivation and hedonic capacity, respectively, likely through different underlying mechanisms. Together, these data show that area scACC-25 has a causal role in consummatory and motivational behaviour and produces rapid responses to the stress hormone cortisol, that mediates anhedonia and anxiety-like behaviour.

Patient Outcomes in Helicopter Emergency Medical Service Documentaries and on Air Ambulance Websites.

Background Helicopter emergency medical service (HEMS) documentaries attract millions of viewers, and publicly available patient stories on Air Ambulance websites are vital to raise awareness and funding for Air Ambulance charities in the United Kingdom (UK). Despite abundant research investigating how fictional programs and news outlets present patient health outcomes, there are no comprehensive studies that investigate how non-fictional HEMS documentaries or Air Ambulance websites present patient outcomes. The aim of this study is to capture the frequency of poor outcomes (mortality) in patients broadcasted on documentaries focusing on HEMS and the patient stories section of UK Air Ambulance websites. Methods A retrospective cohort study reviewed five HEMS documentaries between January 2016 and October 2019 and 20 Air Ambulance websites that had patient stories published until October 2020. In all, 628 patients identified fit the eligibility criteria: 311 from HEMS documentaries and 317 patients from Air Ambulance websites.  Results In all, 0.64% (4/628) of patients died before the hospital, including 0.96% (3/311) of patients on HEMS documentaries and 0.32% (1/317) of patients on Air Ambulance websites. In addition, 2.23% (14/628) of patients died according to their final mention in the data source, including 1.93% (6/311) of patients on HEMS documentaries and 2.52% (8/317) of patients on Air Ambulance websites. Conclusions This study suggests under-reporting of poor patient outcomes in HEMS documentaries and on UK Air Ambulance websites. This could be attributed to the logistical and ethical implications of capturing and presenting poor outcomes but likely impacts upon public perception. Medical professionals should recognize this in order to proactively address potential misconceptions when communicating with patients and their families.

The association of extreme environmental heat with incidence and outcomes of out-of-hospital cardiac arrest in British Columbia: A time series analysis.

Background: The impact of extreme heat on out-of-hospital cardiac arrest (OHCA) incidence and outcomes is under-studied. We investigated OHCA incidence and outcomes over increasing temperatures. Methods: We included non-traumatic EMS (Emergency Medical Services)-assessed OHCAs in British Columbia during the warm seasons of 2020-2021. We fit a time-series quasi-Poisson generalized linear model to estimate the association between temperature and incidence of both EMS-assessed, EMS-treated, and EMS-untreated OHCAs. Second, we employed a logistic regression model to estimate the association between "heatwave" periods (defined as a daily mean temperature > 99th percentile for ≥ 2 consecutive days, plus 3 lag days) with survival and favourable neurological outcomes (cerebral performance category ≤ 2) at hospital discharge. Results: Of 5478 EMS-assessed OHCAs, 2833 were EMS-treated. OHCA incidence increased with increasing temperatures, especially exceeding a daily mean temperature of 25 °C Compared to the median daily mean temperature (16.9 °C), the risk of EMS-assessed (relative risk [RR] 3.7; 95%CI 3.0-4.6), EMS-treated (RR 2.9; 95%CI 2.2-3.9), and EMS-untreated (RR 4.3; 95%CI 3.2-5.7) OHCA incidence were higher during days with a temperature over the 99th percentile. Of EMS-treated OHCAs, during the heatwave (n = 179) and non-heatwave (n = 2654) periods, 4 (2.2%) and 270 (10%) survived and 4 (2.2%) and 241 (9.2%) had favourable neurological outcomes, respectively. Heatwave period OHCAs had decreased odds of survival (adjusted OR 0.28; 95%CI 0.10-0.79) and favourable neurological outcome (adjusted OR 0.31; 95%CI 0.11-0.89) at hospital discharge, compared to other periods. Conclusion: Extreme heat was associated with a higher incidence of OHCA, and lower odds of survival and favourable neurological status at hospital discharge.

Identification of major hemorrhage in trauma patients in the prehospital setting: diagnostic accuracy and impact on outcome.

Background: Hemorrhage is the most common cause of potentially preventable death after injury. Early identification of patients with major hemorrhage (MH) is important as treatments are time-critical. However, diagnosis can be difficult, even for expert clinicians. This study aimed to determine how accurate clinicians are at identifying patients with MH in the prehospital setting. A second aim was to analyze factors associated with missed and overdiagnosis of MH, and the impact on mortality. Methods: Retrospective evaluation of consecutive adult (≥16 years) patients injured in 2019-2020, assessed by expert trauma clinicians in a mature prehospital trauma system, and admitted to a major trauma center (MTC). Clinicians decided to activate the major hemorrhage protocol (MHPA) or not. This decision was compared with whether patients had MH in hospital, defined as the critical admission threshold (CAT+): administration of ≥3 U of red blood cells during any 60-minute period within 24 hours of injury. Multivariate logistical regression analyses were used to analyze factors associated with diagnostic accuracy and mortality. Results: Of the 947 patients included in this study, 138 (14.6%) had MH. MH was correctly diagnosed in 97 of 138 patients (sensitivity 70%) and correctly excluded in 764 of 809 patients (specificity 94%). Factors associated with missed diagnosis were penetrating mechanism (OR 2.4, 95% CI 1.2 to 4.7) and major abdominal injury (OR 4.0; 95% CI 1.7 to 8.7). Factors associated with overdiagnosis were hypotension (OR 0.99; 95% CI 0.98 to 0.99), polytrauma (OR 1.3, 95% CI 1.1 to 1.6), and diagnostic uncertainty (OR 3.7, 95% CI 1.8 to 7.3). When MH was missed in the prehospital setting, the risk of mortality increased threefold, despite being admitted to an MTC. Conclusion: Clinical assessment has only a moderate ability to identify MH in the prehospital setting. A missed diagnosis of MH increased the odds of mortality threefold. Understanding the limitations of clinical assessment and developing solutions to aid identification of MH are warranted. Level of evidence: Level III-Retrospective study with up to two negative criteria. Study type: Original research; diagnostic accuracy study.

Inhibitor of DNA Binding Protein 3 (ID3) and Nuclear Respiratory Factor 1 (NRF1) Mediated Transcriptional Gene Signatures are Associated with the Severity of Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA) is a degenerative vasculopathy. We have previously shown that transcription regulating proteins- inhibitor of DNA binding protein 3 (ID3) and the nuclear respiratory factor 1 (NRF1) contribute to vascular dysregulation. In this study, we have identified sex specific ID3 and NRF1-mediated gene networks in CAA patients diagnosed with Alzheimer's Disease (AD). High expression of ID3 mRNA coupled with low NRF1 mRNA levels was observed in the temporal cortex of men and women CAA patients. Low NRF1 mRNA expression in the temporal cortex was found in men with severe CAA. High ID3 expression was found in women with the genetic risk factor APOE4. Low NRF1 expression was also associated with APOE4 in women with CAA. Genome wide transcriptional activity of both ID3 and NRF1 paralleled their mRNA expression levels. Sex specific differences in transcriptional gene signatures of both ID3 and NRF1 were observed. These findings were further corroborated by Bayesian machine learning and the GeNIe simulation models. Dynamic machine learning using a Monte Carlo Markov Chain (MCMC) gene ordering approach revealed that ID3 was associated with disease severity in women. NRF1 was associated with CAA and severity of this disease in men. These findings suggest that aberrant ID3 and NRF1 activity presumably plays a major role in the pathogenesis and severity of CAA. Further analyses of ID3- and NRF1-regulated molecular drivers of CAA may provide new targets for personalized medicine and/or prevention strategies against CAA.

Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial.

BACKGROUND: In areas co-endemic for Plasmodium vivax and Plasmodium falciparum there is an increased risk of P vivax parasitaemia following P falciparum malaria. Radical cure is currently only recommended for patients presenting with P vivax malaria. Expanding the indication for radical cure to patients presenting with P falciparum malaria could reduce their risk of subsequent P vivax parasitaemia. METHODS: We did a multicentre, open-label, superiority randomised controlled trial in five health clinics in Bangladesh, Indonesia, and Ethiopia. In Bangladesh and Indonesia, patients were excluded if they were younger than 1 year, whereas in Ethiopia patients were excluded if they were younger than 18 years. Patients with uncomplicated P falciparum monoinfection who had fever or a history of fever in the 48 h preceding clinic visit were eligible for enrolment and were required to have a glucose-6-dehydrogenase (G6PD) activity of 70% or greater. Patients received blood schizontocidal treatment (artemether-lumefantrine in Ethiopia and Bangladesh and dihydroartemisinin-piperaquine in Indonesia) and were randomly assigned (1:1) to receive either high-dose short-course oral primaquine (intervention arm; total dose 7 mg/kg over 7 days) or standard care (standard care arm; single dose oral primaquine of 0·25 mg/kg). Random assignment was done by an independent statistician in blocks of eight by use of sealed envelopes. All randomly assigned and eligible patients were included in the primary and safety analyses. The per-protocol analysis excluded those who did not complete treatment or had substantial protocol violations. The primary endpoint was the incidence risk of P vivax parasitaemia on day 63. This trial is registered at ClinicalTrials.gov, NCT03916003. FINDINGS: Between Aug 18, 2019, and March 14, 2022, a total of 500 patients were enrolled and randomly assigned, and 495 eligible patients were included in the intention-to-treat analysis (246 intervention and 249 control). The incidence risk of P vivax parasitaemia at day 63 was 11·0% (95% CI 7·5-15·9) in the standard care arm compared with 2·5% (1·0-5·9) in the intervention arm (hazard ratio 0·20, 95% CI 0·08-0·51; p=0·0009). The effect size differed with blood schizontocidal treatment and site. Routine symptom reporting on day 2 and day 7 were similar between groups. In the first 42 days, there were a total of four primaquine-related adverse events reported in the standard care arm and 26 in the intervention arm; 132 (92%) of all 143 adverse events were mild. There were two serious adverse events in the intervention arm, which were considered unrelated to the study drug. None of the patients developed severe anaemia (defined as haemoglobin <5 g/dL). INTERPRETATION: In patients with a G6PD activity of 70% or greater, high-dose short-course primaquine was safe and relatively well tolerated and reduced the risk of subsequent P vivax parasitaemia within 63 days by five fold. Universal radical cure therefore potentially offers substantial clinical, public health, and operational benefits, but these benefits will vary with endemic setting. FUNDING: Australian Academy of Science Regional Collaborations Program, Bill & Melinda Gates Foundation, and National Health and Medical Research Council.

The association of tibial vs. humeral intraosseous vascular access with patient outcomes in adult out-of-hospital cardiac arrests.

AIM: Humeral and tibial intraosseous (IO) vascular access can deliver resuscitative medications for out-of-hospital cardiac arrest (OHCA), however the optimal site is unclear. We examined the association between IO tibia vs. humerus as the first-attempted vascular access site with OHCA outcomes. METHODS: We used prospectively-collected data from the British Columbia Cardiac Arrest registry, including adult OHCAs treated with IO humerus or IO tibia as the first-attempted intra-arrest vascular access. We fit logistic regression models on the full study cohort and a propensity-matched cohort, to estimate the association between IO site and both favorable neurological outcomes (Cerebral Performance Category 1-2) and survival at hospital discharge. RESULTS: We included 1041 (43%) and 1404 (57%) OHCAs for whom IO humerus and tibia, respectively, were the first-attempted intra-arrest vascular access. Among humerus and tibia cases, 1010 (97%) and 1369 (98%) had first-attempt success, and the median paramedic arrival-to-successful access interval was 6.7 minutes (IQR 4.4-9.4) and 6.1 minutes (IQR 4.1-8.9), respectively. In the propensity-matched cohort (n = 2052), 31 (3.0%) and 44 (4.3%) cases had favourable neurological outcomes in the IO humerus and IO tibia groups, respectively; compared to IO humerus, we did not detect an association between IO tibia with favorable neurological outcomes (OR 1.44; 95% CI 0.90-2.29) or survival to hospital discharge (OR 1.29; 95% CI 0.83-2.01). Results using the full cohort were similar. CONCLUSIONS: We did not detect an association between the first-attempted intra-arrest IO site (tibia vs. humerus) and clinical outcomes. Clinical trials are warranted to test differences between vascular access strategies.

Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

Feasibility and impact of a bespoke pre-hospital point of care ultrasound teaching and training programme at London's air ambulance service.

Introduction: Point-of-care ultrasound has seen an increase in its use in pre-hospital emergency care. There is lack of literature around the training requirement for point-of-care ultrasound of pre-hospital clinicians. This service evaluation assesses the effectiveness of a bespoke hybrid teaching programme. Methods: This is a service evaluation of the point-of-care ultrasound teaching programme at London's Air Ambulance from 1 April to 28 May 2021. Subjects' knowledge, image interpretation and confidence were assessed at two different points. Data were gathered using REDCap and exported to Excel for analysis. Mean values and delta were calculated, and t-test was applied for statistical significance. Results: In total, 57 participants were included; out of which 11 were excluded, as they did not complete a post-course survey. Of these, 41.3% participants were point-of-care ultrasound naïve. Mean pre- and post-course scores were 76.5% and 81.7%, respectively, with an average delta improvement of 5.2% (95% confidence interval = 4.70%-5.68%) which was statistically significant (p < 0.002). There was a statistically significant mean improvement of pre- and post-course scores between point-of-care ultrasound naïve and point-of-care ultrasound experienced groups (p = 0.014). Confidence in using point-of-care ultrasound showed mean overall improvement from 2.36/4 to 3.34/4, a mean difference of 0.98 (95% confidence interval = 0.61-1.34), which was statistically significant (p = 0.0039). Conclusion: Our service evaluation highlighted that a hybrid teaching model used by London's Air Ambulance was feasible and had shown significant improvement in the knowledge, image interpretation and confidence of both the point-of-care ultrasound naïve and the PoCUS experienced cohort of clinicians.

Compartment Syndrome after Crotalid Envenomation in the United States: A Review of the North American Snakebite Registry from 2013 to 2021 on Behalf of the ToxIC Snakebite Study Group.

INTRODUCTION: Compartment syndrome (CS) is a rare but serious complication after crotalid envenomation in the United States. Few data are available regarding the epidemiology and management of these cases. Significant controversy and misunderstanding over best practices, including measurement of compartment pressures and use of fasciotomy, exist for this syndrome. This study aims to describe presentation and management of suspected CS cases after native snakebite reported to the North American Snakebite Registry (NASBR). METHODS: This is an analysis of snakebite cases reported to the Toxicology Investigators Consortium NASBR between January 1, 2013 and December 31, 2021. Cases of native snakebite with documented concern for CS were included. RESULTS: Over an 8-y period, 22 cases of suspected CS were identified, representing 1% of all cases reported to the NASBR. Fasciotomies were performed in 41% (n=9) of these cases, most commonly to the upper extremity (67%, n=6). In cases of suspected CS, intracompartmental pressures (ICPs) were rarely measured (23%, n=5) and fasciotomies were performed without measurement of ICPs frequently (56%, n=5). In 1 case, ICPs were measured and found to be low (8 mm Hg) and fasciotomy was avoided. CONCLUSIONS: Measurement of compartment pressures in cases of suspected CS was uncommon in cases reported to the NASBR. Fasciotomy was commonly performed without measurement of compartment pressures.

Diagnostic accuracy of clinical examination to identify life- and limb-threatening injuries in trauma patients.

BACKGROUND: Timely and accurate identification of life- and limb-threatening injuries (LLTIs) is a fundamental objective of trauma care that directly informs triage and treatment decisions. However, the diagnostic accuracy of clinical examination to detect LLTIs is largely unknown, due to the risk of contamination from in-hospital diagnostics in existing studies. Our aim was to assess the diagnostic accuracy of initial clinical examination for detecting life- and limb-threatening injuries (LLTIs). Secondary aims were to identify factors associated with missed injury and overdiagnosis, and determine the impact of clinician uncertainty on diagnostic accuracy. METHODS: Retrospective diagnostic accuracy study of consecutive adult (≥ 16 years) patients examined at the scene of injury by experienced trauma clinicians, and admitted to a Major Trauma Center between 01/01/2019 and 31/12/2020. Diagnoses of LLTIs made on contemporaneous clinical records were compared to hospital coded diagnoses. Diagnostic performance measures were calculated overall, and based on clinician uncertainty. Multivariate logistic regression analyses identified factors affecting missed injury and overdiagnosis. RESULTS: Among 947 trauma patients, 821 were male (86.7%), median age was 31 years (range 16-89), 569 suffered blunt mechanisms (60.1%), and 522 (55.1%) sustained LLTIs. Overall, clinical examination had a moderate ability to detect LLTIs, which varied by body region: head (sensitivity 69.7%, positive predictive value (PPV) 59.1%), chest (sensitivity 58.7%, PPV 53.3%), abdomen (sensitivity 51.9%, PPV 30.7%), pelvis (sensitivity 23.5%, PPV 50.0%), and long bone fracture (sensitivity 69.9%, PPV 74.3%). Clinical examination poorly detected life-threatening thoracic (sensitivity 48.1%, PPV 13.0%) and abdominal (sensitivity 43.6%, PPV 20.0%) bleeding. Missed injury was more common in patients with polytrauma (OR 1.83, 95% CI 1.62-2.07) or shock (systolic blood pressure OR 0.993, 95% CI 0.988-0.998). Overdiagnosis was more common in shock (OR 0.991, 95% CI 0.986-0.995) or when clinicians were uncertain (OR 6.42, 95% CI 4.63-8.99). Uncertainty improved sensitivity but reduced PPV, impeding diagnostic precision. CONCLUSIONS: Clinical examination performed by experienced trauma clinicians has only a moderate ability to detect LLTIs. Clinicians must appreciate the limitations of clinical examination, and the impact of uncertainty, when making clinical decisions in trauma. This study provides impetus for diagnostic adjuncts and decision support systems in trauma.

Seeing your life story as a Hero's Journey increases meaning in life.

Meaning in life is tied to the stories people tell about their lives. We explore whether one timeless story-the Hero's Journey-might make people's lives feel more meaningful. This enduring story appears across history and cultures and provides a template for ancient myths (e.g., Beowulf) and blockbuster books and movies (e.g., Harry Potter). Eight studies reveal that the Hero's Journey predicts and can causally increase people's experience of meaning in life. We first distill the Hero's Journey into seven key elements-protagonist, shift, quest, allies, challenge, transformation, legacy-and then develop a new measure that assesses the perceived presence of the Hero's Journey narrative in people's life stories: the Hero's Journey Scale. Using this scale, we find a positive relationship between the Hero's Journey and meaning in life with both online participants (Studies 1-2) and older adults in a community sample (Study 3). We then develop a restorying intervention that leads people to see the events of their life as a Hero's Journey (Study 4). This intervention causally increases meaning in life (Study 5) by prompting people to reflect on important elements of their lives and connecting them into a coherent and compelling narrative (Study 6). This Hero's Journey restorying intervention also increases the extent to which people perceive meaning in an ambiguous grammar task (Study 7) and increases their resilience to life's challenges (Study 8). These results provide initial evidence that enduring cultural narratives like the Hero's Journey both reflect meaningful lives and can help to create them. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Adapting international clinical trials during COVID-19 and beyond.

BACKGROUND: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. THE NEW WORKING MODEL: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice-compliant antimalarial trials and foster cross-country and cross-study site collaboration. CONCLUSION: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research.

Performance pressure amplifies the effect of evening detachment on next-morning shame: Downstream consequences for workday cheating behavior.

Detaching from work is beneficial because it helps employees recover from work demands. However, we argue that detachment may be a trade-off for employees in organizations with higher (vs. lower) levels of performance pressure. Drawing on social self-preservation theory, we hypothesize that evening detachment leads employees working in higher (vs. lower) performance pressure work contexts to experience increased shame at work the next morning. In turn, we hypothesize that shame motivates employees to engage in cheating behaviors to covertly inflate their performance and reduce the possibility that others will form negative perceptions of them. In three studies-a 2-week experience sampling study and two experiments-we find that evening detachment leads to heightened next-morning shame in higher (vs. lower) performance pressure work contexts, increasing cheating behavior throughout the workday. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Correlation Between Oncostatin M and Acute Ischemic Stroke: A Case-Control Study.

BACKGROUND: The expression of oncostatin M (OSM) has been studied in various diseases related to inflammatory response, but its implementation in acute ischemic stroke (AIS) remains to be explored.  Objective: The objective of this study is to assess the correlation between serum OSM expression and various aspects of AIS in a clinical setting. MATERIALS AND METHOD: A single-centered case-control study was performed in the First Affiliate Hospital of Chongqing Medical University from October 2020 to March 2021. A total of 134 patients were enrolled in the AIS group and 34 healthy individuals were enrolled in the control group. Physical examinations were performed and venous blood samples were collected. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum OSM. Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, National Institutes of Health Stroke Scale (NIHSS) score, magnetic resonance imaging (MRI) scan, and modified Rankin scale (mRS) were used to assess the classification, etiology, severity, and prognosis of the AIS group. Assessments were done to analyze serum OSM expression based on sensitivity, etiology, severity, prognosis, and several risk factors of AIS. Regression models, correlation, and sensitivity tests were performed to explore the correlation of OSM expression with various aspects of AIS. RESULTS: There was a statistically significant elevation of serum OSM expression in the AIS group (P<0.001). All AIS subgroups showed elevation in OSM level and statistically significant results were reflected in three subgroups. The area under the curve to differentiate AIS patients and control by serum OSM level was 0.747 (P<0.001), with the optimal cut-off value showing sensitivity at 58.82% and specificity at 75.37%. The elevation of serum OSM expression was proportional with severity, not proportional to the volume of infarct, and less elevated in the favorable outcome group. Serum OSM correlation with several risk factors of AIS was statistically significant in age, low-density lipoprotein, non-high-density lipoprotein, prothrombin time, and systolic blood pressure. CONCLUSION: Serum OSM was expressed differently in correlation with various aspects of AIS. Our findings supported the initial hypothesis that OSM is correlated with various aspects of AIS in humans.

A Psychological Resilience Briefing Intervention for Helicopter Emergency Medical Service Observers.

OBJECTIVE: Helicopter emergency medical services (HEMS) observers may be at risk of negative psychological effects associated with exposure to traumatic events during shifts. This article describes a quality improvement project for HEMS observers at Essex & Herts Air Ambulance. METHODS: A psychological resilience briefing intervention (PRBi) was developed and delivered during induction training with 60 HEMS observers. The PRBi aimed to raise awareness of traumatic events that observers may experience and provided basic education on 5 domains, including likely forms of trauma exposure, possible psychological reactions, advice on coping strategies and supporting colleagues, and resources that they could use if required. The intervention was intended to bolster resilience and reduce posttraumatic stress disorder symptoms, and to encourage adaptive coping styles in observers. RESULTS: Observers learned from and valued the PRBi; statistically significant increases were observed in awareness of the 5 domains from pre- to post-delivery, and free-text responses cited a variety of benefits to the observers. There was no indication that the PRBi caused harm. CONCLUSION: The PRBi has now been included in the routine induction of observers at Essex & Herts Air Ambulance and has the potential to be repurposed for use in other settings, including medical schools.

Use of a cow-side oestrus detection test for fertility management in Kenyan smallholder dairy herds.

Background: The use of artificial insemination (AI) has great potential to improve smallholder dairy herds in Africa, however poor success and, in some situations, high costs in Kenya, have been discouraging.  Effective AI requires accurate oestrus detection and the measurement of progesterone (P4) can be used to indicate oestrus as well as non-pregnancy.  A cow-side progesterone lateral flow test, P4 Rapid, was evaluated as an aid to detect oestrus and non-pregnancy in Kenyan dairy cows, and assessed for association with AI efficiency.  Methods: A total of 527 cows were enrolled in the study, from two counties in central and southern Kenya.  Cattle in the test group (n = 308) were presented when suspected to be in oestrus and tested with the P4 Rapid (low P4 = oestrus, medium P4 = inconclusive, high P4 = not in oestrus/pregnant).  Cattle with low P4 were inseminated.  Cattle in the control group (n = 219) were inseminated when oestrus behaviour was detected i.e. standard practice. Results: Of the total P4 Rapid tests performed (n = 745), 1.5% were inconclusive, with the true accuracy of the test between 87-97%.  Conception rates were not significantly higher in the test group (83.9%) compared to the control group (77.9%). Abortion rates were not significantly different between the control (9.5%) and test groups (8.2%).  In the test group, 6.2% (19/308) cows showed a medium or high P4 level on day 0 and nine of these were subsequently found to have been already pregnant. Conclusions: The data indicated that the P4 Rapid test can be a useful tool to assist farmer decision-making in the confirmation of correct timing for AI, and importantly may avoid unnecessary inseminations in pregnant animals, thus reducing the risk of AI-induced abortion.

Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas-a randomized controlled trial (PRIMA).

BACKGROUND: Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. METHODS: This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb<5g/dl and <7g/dl) and/or the risk for blood transfusion, the incidence risk of ≥ 25% fall in haemoglobin with and without haemoglobinuria, and the incidence risk of ≥ 25% fall in haemoglobin to under 7g/dl with and without haemoglobinuria. DISCUSSION: This study evaluates the potential benefit of a universal radical cure for both P. vivax and P. falciparum in different endemic locations. If found safe and effective universal radical cure could represent a cost-effective approach to clear otherwise unrecognised P. vivax infections and hence accelerate P. vivax elimination. TRIAL REGISTRATION: NCT03916003 . Registered on 12 April 2019.

Molecular basis of the association between transcription regulators nuclear respiratory factor 1 and inhibitor of DNA binding protein 3 and the development of microvascular lesions.

The prognosis of patients with microvascular lesions remains poor because vascular remodeling eventually obliterates the lumen. Here we have focused our efforts on vessel dysfunction in two different organs, the lung and brain. Despite tremendous progress in understanding the importance of blood vessel integrity, gaps remain in our knowledge of the underlying molecular factors contributing to vessel injury, including microvascular lesions. Most of the ongoing research on these lesions have focused on oxidative stress but have not found major molecular targets for the discovery of new treatment or early diagnosis. Herein, we have focused on elucidating the molecular mechanism(s) based on two new emerging molecules NRF1 and ID3, and how they may contribute to microvascular lesions in the lung and brain. Redox sensitive transcriptional activation of target genes depends on not only NRF1, but the recruitment of co-activators such as ID3 to the target gene promoter. Our review highlights the fact that targeting NRF1 and ID3 could be a promising therapeutic approach as they are major players in influencing cell growth, cell repair, senescence, and apoptotic cell death which contribute to vascular lesions. Knowledge about the molecular biology of these processes will be relevant for future therapeutic approaches to not only PAH but cerebral angiopathy and other vascular disorders. Therapies targeting transcription regulators NRF1 or ID3 have the potential for vascular disease-modification because they will address the root causes such as genomic instability and epigenetic changes in vascular lesions. We hope that our findings will serve as a stimulus for further research towards an effective treatment of microvascular lesions.