Neuronal pentraxin II is highly upregulated in Parkinson’s disease and a novel component of Lewy bodies

Neuronal pentraxin II (NPTX2) is the most highly upregulated gene in the Parkinsonian substantia nigra based on our whole genome expression profiling results. We show here that it is a novel component of Lewy bodies and Lewy neurites in sporadic Parkinson’s disease (PD). NPTX2 is also known as the neuronal activity-regulated protein (Narp), which is secreted and involved in long-term neuronal plasticity. Narp further regulates AMPA receptors which have been found to mediate highly selective non-apoptotic cell death of dopaminergic neurons. NPTX2/Narp is found in close association with alpha-synuclein aggregates in both substantia nigra and cerebral cortex in PD but unlike alpha-synuclein gene expression, which is down-regulated in the Parkinsonian nigra, NPTX2 could represent a driver of the disease process. In view of its profound (>800%) upregulation and its established role in synaptic plasticity as well as dopaminergic nerve cell death, NPTX2 is a very interesting novel player which is likely to be involved in the pathway dysregulation which underlies PD

Developmentally Supportive Care in Congenital Heart Disease: A Concept Analysis

Theoretical principlesImproved survival of infants and children with congenital heart disease experience has led to recognition that up to half of congenital heart disease survivors also experience developmental delay. Developmentally supportive care is a care model shown in Neonatal Intensive Care Units to be associated with improved outcomes, but developmentally supportive practices with premature infants may not be equally effective in the cardiac population that includes all ages.Phenomena addressedThe purpose of this paper is to present a concept analysis using the Walker and Avant method in order to identify and define characteristics of developmentally supportive care as it may be applied to the population of neonates, infants, and children with congenital heart disease. A theoretical definition of developmentally supportive care is presented.Research linkagesThis concept analysis will provide nurses and allied health professionals with a theoretical basis to implement high quality, family-centered care that meets individual developmental needs in a population at high risk for developmental sequelae. Nursing implications for developmentally supportive care as it applies to infants and children with heart disease are discussed

Affirmative critique as minor qualitative critical inquiry: A storying of a becoming critical engagement with what happens

In response to the evolving nature of scholarly exchange and collaboration, University of California Press allows its authors to post preprints and postprints on authors' personal websites, and within institutional repositories. You may use the Publisher-generated PDF, and you must display the following Publisher's Statement in tandem with posting: Published as [Andersen, Camilla Eline. (2017). Affirmative critique as minor qualitative critical inquiry: A storying of a becoming critical engagement with what happens. International review of Qualitative Research, 10(4), 430-449. doi: http://dx.doi.org10.1525/irqr.2017.10.4.430]. © [2017] by [the Regents of the University of California/Sponsoring Society or Association]. Copying and permissions notice: Authorization to copy this content beyond fair use (as specified in Sections 107 and 108 of the U. S. Copyright Law) for internal or personal use, or the internal or personal use of specific clients, is granted by [the Regents of the University of California/on behalf of the Sponsoring Society] for libraries and other users, provided that they are registered with and pay the specified fee via Rightslink® or directly with the Copyright Clearance Center (http://www.copyright.com/).publishedVersio

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

One-pot cross-coupling/C–H functionalization reactions: Quinoline as a substrate and ligand through N–Pd interaction

Herein, we report a one-pot process that marries mechanistically distinct, traditional cross-coupling reactions with C–H functionalization using the same precatalyst. The reactions proceed in yields of up to 95%, in air, and require no extraneous ligand. The reactions are thought to be facilitated by harnessing the substrate quinoline as an N-ligand, and evidence of the palladium–quinoline interaction is provided by 1H-15N HMBC NMR spectroscopy and X-ray crystallographic structures. Application of the methodology is demonstrated by the quick formation of fluorescent, π-extended frameworks.<br/

Hepatitis B infection: surveillance and control in the Eastern Health Board, from policy to practice.

Hepatitis B infection may result in serious illness and death. Although Ireland has a relatively low rate of hepatitis B infection, notifications of the disease have risen in the Eastern Health Board (EHB) region in the past two years. Adequate control of hepatitis B at population level is dependent upon good systems for surveillance and contact tracing, as well as implementation of appropriate immunisation programmes. A safe and effective hepatitis B vaccine is available. This report makes several recommendations in regard to hepatitis B in the EHB. The National Immunisation Guidelines on Hepatitis B Virus (HBV) vaccination should be fully implemented in the EHB, with a nationally agreed arrangement whereby GPs are paid to deliver HBV vaccine free to their at-risk patients, regardless of general medical services eligibility. The report also calls for an audit of vaccination uptake by the relevant EHB services, a HBV surveillance and contact tracing service at Area Health Board (AHB) level, delivered by a designated Area Medical Officer and a contact tracer, and supported by a clerical officer and co-ordination at EHB level by a designated specialist in Public Health Medicine

Unhealthy habits persist:The ongoing presence of modifiable risk factors for disease in women

<div><p>Objectives</p><p>Vascular disease remains a leading cause of death. There are several vascular risk factors identified that can mitigate development of disease in ageing. We examine reported rates of modifiable risk factors in women responding to an online health questionnaire advertised by popular media.</p><p>Methods</p><p>A sample of 26 620 women aged over 18 was examined in 2015 with a cross-sectional health questionnaire. The questionnaire included self-reported health, mood, lifestyle and vascular risk factors.</p><p>Results</p><p>There remains high rates of modifiable risk factors present in women. The vast majority of women (80%) reported not eating enough fruit and vegetables. Compared to the guidelines for health, the majority did not perform enough weekly physical activity (70%) and more than half the participants were overweight (54%). Sufficient fruit, vegetables, fish, legumes and physical activity were reported in less than 30% of women!</p><p>Conclusions</p><p>Women continue to report low rates of physical activity, fruit and vegetable intake and higher BMI than recommended for good health, despite worldwide health promotion activities aimed at changing these lifestyle factors. Programs to support healthy living need to be reviewed and revised to reduce the burden of vascular disease and dementia in women. Previous guidelines are not having the important impact they should, particularly in women.</p></div