Monosynaptic Rabies Tracing Reveals Sex- and Age-Dependent Dorsal Subiculum Connectivity Alterations in an Alzheimer's Disease Mouse Model.

The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD circuit-based mechanisms, we mapped synaptic circuit inputs to dorsal SUB using monosynaptic rabies tracing in the 5xFAD mouse model by quantitatively comparing the circuit connectivity of SUB excitatory neurons in age-matched controls and 5xFAD mice at different ages for both sexes. Input-mapped brain regions include the hippocampal subregions (CA1, CA2, CA3), medial septum and diagonal band, retrosplenial cortex, SUB, postsubiculum (postSUB), visual cortex, auditory cortex, somatosensory cortex, entorhinal cortex, thalamus, perirhinal cortex (Prh), ectorhinal cortex, and temporal association cortex. We find sex- and age-dependent changes in connectivity strengths and patterns of SUB presynaptic inputs from hippocampal subregions and other brain regions in 5xFAD mice compared with control mice. Significant sex differences for SUB inputs are found in 5xFAD mice for CA1, CA2, CA3, postSUB, Prh, lateral entorhinal cortex, and medial entorhinal cortex: all of these areas are critical for learning and memory. Notably, we find significant changes at different ages for visual cortical inputs to SUB. While the visual function is not ordinarily considered defective in AD, these specific connectivity changes reflect that altered visual circuitry contributes to learning and memory deficits. Our work provides new insights into SUB-directed neural circuit mechanisms during AD progression and supports the idea that neural circuit disruptions are a prominent feature of AD.

Experience in an Urban Level 1 Trauma Center With Tranexamic Acid in Pediatric Trauma: A Retrospective Chart Review.

BACKGROUND: Evidence for tranexamic acid (TXA) in the pharmacologic management of trauma is largely derived from data in adults. Guidance on the use of TXA in pediatric patients comes from studies evaluating its use in cardiac and orthopedic surgery. There is minimal data describing TXA safety and efficacy in pediatric trauma. The purpose of this study is to describe the use of TXA in the management of pediatric trauma and to evaluate its efficacy and safety end points. METHODS: This retrospective, observational analysis of pediatric trauma admissions at Hennepin County Medical Center from August 2011 to March 2019 compares patients who did and did not receive TXA. The primary end point is survival to hospital discharge. Secondary end points include surgical intervention, transfusion requirements, length of stay, thrombosis, and TXA dose administered. RESULTS: There were 48 patients aged ≤16 years identified for inclusion using a massive transfusion protocol order. Twenty-nine (60%) patients received TXA. Baseline characteristics and results are presented as median (interquartile range) unless otherwise specified, with statistical significance defined as P < .05. Patients receiving TXA were more likely to be older, but there was no difference in injury type or Injury Severity Score at baseline. There was no difference in survival to discharge or thrombosis. Patients who did not receive TXA had numerically more frequent surgical intervention and longer length of stay, but these did not reach significance. CONCLUSIONS: TXA was utilized in 60% of pediatric trauma admissions at a single level 1 trauma center, more commonly in older patients. Although limited by observational design, we found patients receiving TXA had no difference in mortality or thrombosis.

The neuropathology of fatal cerebral malaria in malawian children.

We examined the brains of 50 Malawian children who satisfied the clinical definition of cerebral malaria (CM) during life; 37 children had sequestration of infected red blood cells (iRBCs) and no other cause of death, and 13 had a nonmalarial cause of death with no cerebral sequestration. For comparison, 18 patients with coma and no parasitemia were included. We subdivided the 37 CM cases into two groups based on the cerebral microvasculature pathology: iRBC sequestration only (CM1) or sequestration with intravascular and perivascular pathology (CM2). We characterized and quantified the axonal and myelin damage, blood-brain barrier (BBB) disruption, and cellular immune responses and correlated these changes with iRBC sequestration and microvascular pathology. Axonal and myelin damage was associated with ring hemorrhages and vascular thrombosis in the cerebral and cerebellar white matter and brainstem of the CM2 cases. Diffuse axonal and myelin damage were present in CM1 and CM2 cases in areas of prominent iRBC sequestration. Disruption of the BBB was associated with ring hemorrhages and vascular thrombosis in CM2 cases and with sequestration in both CM1 and CM2 groups. Monocytes with phagocytosed hemozoin accumulated within microvessels containing iRBCs in CM2 cases but were not present in the adjacent neuropil. These findings are consistent with a link between iRBC sequestration and intravascular and perivascular pathology in fatal pediatric CM, resulting in myelin damage, axonal injury, and breakdown of the BBB.

Twelve tips for teaching in a provincially distributed medical education program.

BACKGROUND: As distributed undergraduate and postgraduate medical education becomes more common, the challenges with the teaching and learning process also increase. AIM: To collaboratively engage front line teachers in improving teaching in a distributed medical program. METHOD: We recently conducted a contest on teaching tips in a provincially distributed medical education program and received entries from faculty and resident teachers. RESULTS: Tips that are helpful for teaching around clinical cases at distributed teaching sites include: ask "what if" questions to maximize clinical teaching opportunities, try the 5-min short snapper, multitask to allow direct observation, create dedicated time for feedback, there are really no stupid questions, and work with heterogeneous group of learners. Tips that are helpful for multi-site classroom teaching include: promote teacher-learner connectivity, optimize the long distance working relationship, use the reality television show model to maximize retention and captivate learners, include less teaching content if possible, tell learners what you are teaching and make it relevant and turn on the technology tap to fill the knowledge gap. CONCLUSION: Overall, the above-mentioned tips offered by front line teachers can be helpful in distributed medical education.

Career resilience of the tourism and hospitality workforce in the COVID-19: The protection motivation theory perspective.

By applying the protection motivation theory, the study aims to investigate factors influencing tourism and hospitality (T&H) workers' career resilience when faced with health-related risks at work during a pandemic. Data were collected from 495 part-time and full-time employees in the Vietnamese tourism and hospitality sector. The study found that workers' perceived vulnerability and perceived severity of the pandemic were positively associated with career resilience. Perceived severity was positively related to self-efficacy and response efficacy, while perceived vulnerability was positively associated with self-efficacy only. Both self-efficacy and response efficacy positively influenced career resilience through the mediating role of health risk preventative behavior. Theoretically, the study advances the stream of research in resilience in general and career resilience in particular among T&H workers when faced with a health-related crisis. Practical implications are provided with recommendations on how to facilitate career resilience among T&H employees working in the current high-risk environment.

Racial Disparities and Mental Health Effects Within Prostate Cancer.

Disparities in prostate cancer (PCa) exist at all stages: screening, diagnosis, treatment, outcomes, and mortality. Although there are a multitude of complex biological (e.g., genetics, age at diagnosis, PSA levels, Gleason score) and nonbiological (e.g., socioeconomic status, education level, health literacy) factors that contribute to PCa disparities, nonbiological factors may play a more significant role. One understudied aspect influencing PCa patients is mental health related to the quality of life. Overall, PCa patients report poorer mental health than non-PCa patients and have a higher incidence of depression and anxiety. Racial disparities in mental health, specifically in PCa patients, and how poor mental health impacts overall PCa outcomes require further study.

Enhanced infection control interventions reduced catheter-related bloodstream infections in the neonatal department of Hung Vuong Hospital, Vietnam, 2011-2012: a pre- and post-intervention study.

Background: Catheter-related bloodstream infections (CR-BSI) cause high neonatal mortality and are related to inadequate aseptic technique during the care and maintenance of a catheter. The incidence of CR-BSI among neonates in Hung Vuong Hospital was higher than that of other neonatal care centres in Vietnam. Methods: An 18-month pre- and post-intervention study was conducted over three 6-month periods to evaluate the effectiveness of the intervention for CR-BSI and to identify risk factors associated with CR-BSI. During the intervention period, we trained all nurses in the Department of Neonatology on BSI preventive practices, provided auditing and feedback about aseptic technique during catheter care and maintenance, and reorganised preparation of total parenteral nutrition. All neonates with intravenous catheter insertion ≥48 h in the pre- and post-intervention period were enrolled. A standardised questionnaire was used to collect data. Blood samples were collected for cultures. We used Poisson regression to calculate rate ratio (RR) and 95% confidence interval (CI) for CR-BSI incidence rates and logistic regression to identify risk factors associated with CR-BSI. Results: Of 2225 neonates enrolled, 1027 were enrolled in the pre-intervention period, of which 53 CR-BSI cases occurred in 8399 catheter-days, and 1198 were enrolled in the post-intervention period, of which 32 CR-BSI cases occurred in 8324 catheter-days. Incidence rates of CR-BSI significantly decreased after the intervention (RR = 0.61, 95% CI 0.39-0.94). Days of hospitalisation, episodes of non-catheter-related hospital-acquired infections, and the proportion of deaths significantly decreased after the intervention (p < 0.01). The CR-BSI was associated with days of intravenous catheter (odds ratio [OR] = 1.05, 95% CI 1.03-1.08), use of endotracheal intubation (OR = 2.27, 95% CI 1.27-4.06), and intravenous injection (OR = 8.50, 95% CI 1.14-63.4). Conclusions: The interventions significantly decreased the incidence rate of CR-BSI. Regular refresher training and auditing and feedback about aseptic technique during care and maintenance of catheters are critical to reducing CR-BSI.

Characterization of Solanum melongena Thioesterases Related to Tomato Methylketone Synthase 2.

2-Methylketones are involved in plant defense and fragrance and have industrial applications as flavor additives and for biofuel production. We isolated three genes from the crop plant Solanum melongena (eggplant) and investigated these as candidates for methylketone production. The wild tomato methylketone synthase 2 (ShMKS2), which hydrolyzes ß-ketoacyl-acyl carrier proteins (ACP) to release ß-ketoacids in the penultimate step of methylketone synthesis, was used as a query to identify three homologs from S. melongena: SmMKS2-1, SmMKS2-2, and SmMKS2-3. Expression and functional characterization of SmMKS2s in E. coli showed that SmMKS2-1 and SmMKS2-2 exhibited the thioesterase activity against different ß-ketoacyl-ACP substrates to generate the corresponding saturated and unsaturated ß-ketoacids, which can undergo decarboxylation to form their respective 2-methylketone products, whereas SmMKS2-3 showed no activity. SmMKS2-1 was expressed at high level in leaves, stems, roots, flowers, and fruits, whereas expression of SmMKS2-2 and SmMKS2-3 was mainly in flowers and fruits, respectively. Expression of SmMKS2-1 was induced in leaves by mechanical wounding, and by methyl jasmonate or methyl salicylate, but SmMKS2-2 and SmMKS2-3 genes were not induced. SmMKS2-1 is a candidate for methylketone-based defense in eggplant, and both SmMKS2-1 and SmMKS2-2 are novel MKS2 enzymes for biosynthesis of methylketones as feedstocks to biofuel production.

A new window of opportunity in echocardiography.

BACKGROUND: Improvements in echocardiographic technology have made technically difficult studies a rare entity. However, physical barriers such as bandages, inability for patients to turn because of intubation, arterial lines, and organ and life support machines make echocardiographic imaging challenging. METHODS: We performed echocardiographic imaging from left and right posterior thoracic approach using acoustic properties of pleural fluid to assist in obtaining good imaging windows in patients who had pleural effusion (PE). In this study we describe one author's (T. Z. N.) experience with the mid to lower posterior thoracic window in 18 patients who had PE and in whom conventional transthoracic windows either provided suboptimal images or incomplete clinical information. RESULTS: The posterior approach allowed excellent differentiation of pericardial effusion versus PE, detection of pericardial disease and pericardial infiltration, and excellent endocardial border definition of left and right ventricle in those with poor anterior transthoracic windows. Native and prosthetic aortic valve gradients could be assessed adequately as a result of perfectly parallel Doppler alignment beam to left ventricular outflow tract and aortic valve. In addition, right posterior thoracic window provided views comparable with subcostal view and allowed visualization of inferior vena cava, right atrium, and liver. CONCLUSION: In patients with PE, imaging from low to midposterior thorax can provide additional diagnostic echocardiographic images and should be used in patients in whom conventional images are technically difficult or require additional information.