Caring for Colleagues Who Have Experienced Loss

Loss and grief are challenging enough in “normal” times, but with the pandemic, it seems that everyone has undergone some sort of loss. For many who have experienced the loss of health, a loved one, a relationship, or other significant parts of their lives, the pandemic has exacerbated the challenges. UD’s mission references “educating the whole person and linking learning and scholarship with leadership and service.” In what ways can we rediscover the link between the vast scholarship on grief and our service to others who are experiencing that grief? How can we demonstrate the family spirit and care for our colleagues who have experienced loss? What resources are helpful for those supporting others in grief? Join a discussion where we pool our knowledge and dig into what we can learn about helping those around us who are grieving loss

Teachers' concerns about pupils' mental health in a cross-sectional survey of a population sample of British schoolchildren.

BACKGROUND: Schools are becoming central to the identification and referral of children and young people with poor mental health. Understanding how well a teacher concern predicts mental disorder in a child or young person is important for mental health teams who need to respond to referrals. METHOD: This secondary analysis of the 2004 British Child and Adolescent Mental Health Survey used the first item of the Strengths and Difficulties Questionnaire (SDQ) Impact subscale to indicate concern about a child or young person's mental health. Mental disorder according to DSM IVR criteria was assessed using the multi-informant Development and Well-Being Assessment. We compared the proportion with and without mental disorder according to the presence or absence of teacher concern. RESULTS: Teacher concern was moderately predictive (49% with teacher concern had a disorder) and sensitive (teacher concern present among 56% with disorder), while lack of teacher concern was highly predictive (only 5% had disorder) and specific (94% no disorder). Teacher concern was associated with significantly poorer mental health (mean teacher SDQ total difficulty score 19.6, SD 5.6 with disorder, mean 15.0; SD 5.1 if no disorder) compared to children without teacher concern (mean 9.6, SD 5.5 with disorder, and 4.9; SD 4.3 if no disorder; F (3, 5,931) = 1527.228, p = .001). If both teacher and parents were concerned, the child or young person was much more likely to have a disorder. CONCLUSION: A lack of teacher concern can reassure mental health practitioners in the vast majority of cases. While teacher concern does identify those with poorer mental health, it is only moderately predictive of a disorder. When concerned about a child or young person, discussions with parents or others who know them may help teachers identify those who most need support. KEY PRACTITIONER MESSAGE: The emphasis on schools as a major setting to provide support and identify the need for referral to specialist mental health services means service commissioners, providers and practitioners could benefit from insight into how predictive a teacher's concern is of childhood mental health conditions and how this may vary with the type of disorder If teachers are not concerned about a child, practitioners can be reassured that there is unlikely to be a significant problem with their mental health, although this will be less certain in schools whose pupils are likely to have a higher than average levels of difficulty Teacher concerns do not necessarily differentiate between clinically impairing and mild/ moderate mental health difficulties, but do identify children in poorer mental health Asking for corroboration of concern from other sources increases the strength of the association to severe mental health disorders.Place2be Governments of England, Scotland, Wale

Expression of Six Drug Transporters in Vaginal, Cervical, and Colorectal Tissues: Implications for Drug Disposition in HIV Prevention

Effective antiretroviral (ARV)-based HIV prevention strategies require optimizing drug exposure in mucosal tissues; yet factors influencing mucosal tissue disposition remain unknown. We hypothesized drug transporter expression in vaginal, cervical, and colorectal tissues is a contributing factor and selected 3 efflux (ABCB1/MDR1, ABCC2/MRP2, ABCC4/MRP4) and 3 uptake (SLC22A6/OAT1, SLC22A8/OAT3, SLCO1B1/OATP1B1) transporters to further investigate based on their affinity for 2 ARVs central to prevention (tenofovir, maraviroc). Tissue was collected from 98 donors. mRNA and protein expression were quantified using qPCR and immunohistochemistry (IHC). Hundred percent of tissues expressed efflux transporter mRNA. IHC localized them to the epithelium and/or submucosa. Multivariable analysis adjusted for age, smoking, and co-medications revealed significant (P  colorectal; vaginal ABCC2 2.9-fold > colorectal; colorectal ABCC4 2.0-fold > cervical). In contrast, uptake transporter mRNA was expressed in <25% of tissues. OAT1 protein was detected in 0% of female genital tissues and in 100% of colorectal tissues, but only in rare epithelial cells. These data support clinical findings of higher maraviroc and tenofovir concentrations in rectal tissue compared to vaginal or cervical tissue after oral dosing. Quantifying mucosal transporter expression and localization can facilitate ARV selection to target these tissues

Academic-community partnerships improve outcomes in pediatric trauma care

BackgroundTo address the specialized needs of injured children, pediatric trauma centers (PTCs) were established at many large, academic hospitals. This study explores clinical outcomes observed for injured children treated at an academic-sponsored community facility.MethodsIn partnership with an academic medical center in a major metropolitan area, a not-for-profit community hospital became a designated Level II PTC in October 2010. Data for injured children &lt;15 years old treated prior to PTC designation from January 2000 to September 2010 were prospectively collected using the Trauma and Emergency Medicine Information System and compared to data collected after PTC designation from January 2011 to December 2013.ResultsOverall, 681 injured children were treated at the community hospital from January 2011 to December 2013. Children treated after PTC designation were less likely to undergo computed tomography (CT) (50.9% vs. 81.3%, p&lt;0.01), even when controlling for age, gender, injury type, injury severity, and year (OR 0.18, 95%CI 0.08-0.37). Specifically, fewer head (45.7% vs. 68.7%, p&lt;0.01) and abdominal CTs (13.2% vs. 26.5%, p&lt;0.01) were performed. Hospital length of stay was significantly shorter (2.8 ± 3.7 days vs. 3.7 ± 5.9 days, p&lt;0.01). Mortality was low overall, but also decreased after PTC designation (0.4% vs. 2.0%, p=0.02).ConclusionsThese results indicate that academic-community partnerships in pediatric trauma care are a feasible alternative and may lead to improved outcomes for injured children

Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina.Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome