Primary care physicians’ understanding and utilization of pediatric exome sequencing results

Optimizing exome sequencing (ES) utility requires effective communication and collaboration between primary care physicians (PCPs) and genetics healthcare providers (GHP). To explore how PCPs use ES results to coordinate multipart management plans for complex pediatric patients, we assessed result understanding and utilization. Twenty‐seven PCPs of pediatric patients with ES results from a genetics clinic completed a mixed methods 45‐question survey measuring perceived genetics knowledge, confidence performing genetics tasks, understanding of ES technology and results, and expectations of GHP. Quantitative and qualitative data analysis classified by ES result types generated descriptive statistics, Pearson correlation coefficients, and common themes. Forty‐five‐percent of PCPs interpreted variant of uncertain significance results as diagnostic (implementing management changes and recommending familial testing). Most PCPs (85%) identified positive ES results impacts, but only 65% indicated ES was beneficial to care. The majority (74%) expected GHP and patients’ families to assume follow‐up care responsibility and future ES results re‐interpretations. Limited knowledge may be a factor, as 59% desired more patient care information from GHP. Our results suggest optimizing continuity of care and collaboration for pediatric patients with ES results requires additional communication between GHP and PCPs, along with continuing genetics education for PCPs aimed at improving genetic literacy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153256/1/jgc41163-sup-0001-DATAS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153256/2/jgc41163_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153256/3/jgc41163.pd

Attention and Recall of Point-of-sale Tobacco Marketing: A Mobile Eye-Tracking Pilot Study

Introduction: As tobacco advertising restrictions have increased, the retail ‘power wall’ behind the counter is increasingly invaluable for marketing tobacco products. Objective: The primary objectives of this pilot study were 3-fold: (1) evaluate the attention paid/fixations on the area behind the cash register where tobacco advertising is concentrated and tobacco products are displayed in a real-world setting, (2) evaluate the duration (dwell-time) of these fixations, and (3) evaluate the recall of advertising displayed on the tobacco power wall. Methods: Data from 13 Smokers (S) and 12 Susceptible or non-daily Smokers (SS) aged 180–30 from a mobile eye-tracking study. Mobile-eye tracking technology records the orientation (fixation) and duration (dwell-time) of visual attention. Participants were randomized to one of three purchase tasks at a convenience store: Candy bar Only (CO; N = 10), Candy bar + Specified cigarette Brand (CSB; N = 6), and Candy bar + cigarette Brand of their Choice (CBC; N = 9). A post-session survey evaluated recall of tobacco marketing. Key outcomes were fixations and dwell-time on the cigarette displays at the point-of-sale. Results: Participants spent a median time of 44 seconds during the standardized time evaluated and nearly three-quarters (72%) fixated on the power wall during their purchase, regardless of smoking status (S: 77%, SS: 67%) or purchase task (CO: 44%, CSB: 71%, CBC: 100%). In the post session survey, nearly all participants (96%) indicated they noticed a cigarette brand and 64% were able to describe a specific part of the tobacco wall or recall a promotional offer. Conclusions: Consumers are exposed to point-of-sale tobacco marketing, regardless of smoking status. FDA should consider regulations that limit exposure to point-of-sale tobacco marketing among consumers

Chemistry and biology of asparagine-linked glycosylation

The biosynthesis of glycoprotein conjugates is a complex process that involves the collective action of numerous enzymes. Recent research on the chemistry and biology of asparagine-linked glycosylation in our group has been focused on two specific areas. These are the development of potent inhibitors of oligosaccharyl transferase and the investigation of the conformational consequences of the glycosylation process. Since asparagine-linked glycosylation is an essential eukaryotic process, an understanding of the details of this complex transformation is of utmost importance both to fundamental biochemistry and to a consideration of the mechanisms of homeostatic control

Predicting suicidal ideation in a nationally representative sample of young adults: a 12-month prospective study

Background Evidence-based theoretical models outlining the pathways to the development of suicidal ideation may inform treatment. The current research draws from the Interpersonal Theory of Suicide (IPT) and the Integrated Motivational-Volitional (IMV) Model of suicidal behaviour, and aims to test the interaction between perceived burdensomeness and thwarted belongingness as proposed by the IPT model, and the defeat–entrapment pathway as proposed by the IMV model, in the prediction of suicidal ideation at 12-month follow-up. Methods The Scottish Wellbeing Study is a nationally representative prospective study of young people aged 18–34 years (n = 3508) from across Scotland, who completed a baseline interview and a 12-month follow-up (n = 2420). The core factors from both the IPT (perceived burdensomeness and thwarted belongingness) and the IMV model (defeat, internal and external entrapment) were measured alongside demographics, depressive symptoms and suicidal ideation at baseline. At 12-month follow-up suicidal ideation was assessed again. Results In multiple regression analysis perceived burdensomeness and internal entrapment, with baseline suicidal ideation, predicted 12-month suicidal ideation. No support for the interaction between perceived burdensomeness and thwarted belongingness in predicting 12-month suicidal ideation was found. However, there was evidence that internal, but not external, entrapment mediated the relationship between defeat and 12-month suicidal ideation, but no support was found for the moderation of burdensomeness and belongingness on the entrapment to suicidal ideation pathway. Conclusions The current findings highlight the importance of targeting perceived burdensomeness and internal entrapment to reduce the likelihood that suicidal ideation emerges in at risk individuals.Output Status: Forthcoming/Available Onlin

Improving psychological science: further thoughts, reflections and ways forward

Cogent Psychology is a pioneering and dynamic Open Access journal for the psychology community, publishing original research, reviews, and replications that span the full spectrum of psychological inquiry. In 2021, it relaunched with a new Editor-in-Chief and Section Editors with an exciting vision to combine open access publishing with open research practices. As such, the journal welcomes traditional and new article formats, including Registered Reports, Brief Replication Reports, Review Articles, and Brief Reports. This broader range of formats is designed to reflect the evolving nature of psychological research and open science approaches. To the best of our knowledge, no other psychology journal offers such a distinctive combination of article publishing formats. Moreover, we welcome submissions in nine key areas of psychological science: Clinical Psychology, Cognitive & Experimental Psychology, Developmental Psychology, Educational Psychology, Health Psychology, Neuropsychology, Personality & Individual Differences, Social Psychology and Work, Industrial & Organisational Psychology

A workplace Acceptance and Commitment Therapy (ACT) intervention for improving healthcare staff psychological distress : a randomised controlled trial

The levels of psychological distress and burnout among healthcare staff are high, with negative implications for patient care. A growing body of evidence indicates that workplace programmes based on Acceptance and Commitment Therapy (ACT) are effective for improving employees’ general psychological health. However, there is a paucity of research examining the specific psychological and/or behavioural processes through which workplace ACT programmes transmit their beneficial effects. The aim of this randomised controlled trial was to investigate the outcomes and putative processes of change in a 4-session ACT training programme designed to reduce psychological distress among healthcare staff (n = 98). Ninety-eight employees of a healthcare organisation were randomly allocated to the ACT intervention or to a waiting list control group. Study measures were administered on four occasions (baseline, mid-intervention, post-intervention, and follow-up) over a three-month evaluation period. Results showed that the ACT intervention led to a significant decrease in symptoms of psychological distress and a less pronounced reduction in burnout. These effects were mediated primarily via an improvement in mindfulness skills and values-based behaviour and moderated by participants’ initial levels of distress. At four-week post-intervention, 48% of participants who received the ACT intervention showed reliable improvements in psychological distress, with just under half of the aforementioned improvements (46.15%) meeting criteria for clinically significant change. The results advance ACT as an effective stress management intervention for healthcare staff. The findings should be confirmed in a large scale randomised controlled trial with longer follow-up and cost-effectiveness analyses

Biocatalytic routes to stereo-divergent iridoids

Thousands of natural products are derived from the fused cyclopentane-pyran molecular scaffold nepetalactol. These natural products are used in an enormous range of applications that span the agricultural and medical industries. For example, nepetalactone, the oxidized derivative of nepetalactol, is known for its cat attractant properties as well as potential as an insect repellent. Most of these naturally occurring nepetalactol-derived compounds arise from only two out of the eight possible stereoisomers, 7S-cis-trans and 7R-cis-cis nepetalactols. Here we use a combination of naturally occurring and engineered enzymes to produce seven of the eight possible nepetalactol or nepetalactone stereoisomers. These enzymes open the possibilities for biocatalytic production of a broader range of iridoids, providing a versatile system for the diversification of this important natural product scaffold

Primary care medication safety surveillance with integrated primary and secondary care electronic health records: a cross-sectional study

Introduction: The extent of preventable medication-related hospital admissions and medication-related issues in primary care is significant enough to justify developing decision support systems for medication safety surveillance. The prerequisite for such systems is defining a relevant set of medication safety-related indicators and understanding the influence of both patient and general practice characteristics on medication prescribing and monitoring. Objective: The aim of the study was to investigate the feasibility of linked primary and secondary care electronic health record data for surveillance of medication safety, examining not only prescribing but also monitoring, and associations with patient- and general practice-level characteristics. Methods: A cross-sectional study was conducted using linked records of patients served by one hospital and over 50 general practices in Salford, UK. Statistical analysis consisted of mixed-effects logistic models, relating prescribing safety indicators to potential determinants. Results: The overall prevalence (proportion of patients with at least one medication safety hazard) was 5.45 % for prescribing indicators and 7.65 % for monitoring indicators. Older patients and those on multiple medications were at higher risk of prescribing hazards, but at lower risk of missed monitoring. The odds of missed monitoring among all patients were 25 % less for males, 50 % less for patients in practices that provide general practitioner training, and threefold higher in practices serving the most deprived compared with the least deprived areas. Practices with more prescribing hazards did not tend to show more monitoring issues. Conclusions:Systematic collection, collation, and analysis of linked primary and secondary care records produce plausible and useful information about medication safety for a health system. Medication safety surveillance systems should pay close attention to patient age and polypharmacy with respect to both prescribing and monitoring failures; treat prescribing and monitoring as different statistical processes, rather than a combined measure of prescribing safety; and audit the socio-economic equity of missed monitoring

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targetedpanel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations

Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease

The immune mechanisms mediating COVID-19 vaccine attenuation of COVID-19 remain undescribed. We conducted comprehensive analyses detailing immune responses to SARS-CoV-2 virus in blood post-vaccination with ChAdOx1 nCoV-19 or a placebo. Samples from randomised placebo-controlled trials (NCT04324606 and NCT04400838) were taken at baseline, onset of COVID-19-like symptoms, and 7 days later, confirming COVID-19 using nucleic amplification test (NAAT test) via real-time PCR (RT-PCR). Serum cytokines were measured with multiplexed immunoassays. The transcriptome was analysed with long, short and small RNA sequencing. We found attenuation of RNA inflammatory signatures in ChAdOx1 nCoV-19 compared with placebo vaccinees and reduced levels of serum proteins associated with COVID-19 severity. KREMEN1, a putative alternative SARS-CoV-2 receptor, was downregulated in placebo compared with ChAdOx1 nCoV-19 vaccinees. Vaccination ameliorates reductions in cell counts across leukocyte populations and platelets noted at COVID-19 onset, without inducing potentially deleterious Th2-skewed immune responses. Multi-omics integration links a global reduction in miRNA expression at COVID-19 onset to increased pro-inflammatory responses at the mRNA level. This study reveals insights into the role of COVID-19 vaccines in mitigating disease severity by abrogating pro-inflammatory responses associated with severe COVID-19, affirming vaccine-mediated benefit in breakthrough infection, and highlighting the importance of clinically relevant endpoints in vaccine evaluation