Hastingsvoss7259

Alopecia areata (AA) is a common cause of immune-mediated non-scarring hair loss. Links between AA and common mental health, autoimmune and atopic conditions, and common infections have previously been described but remain incompletely elucidated and contemporary descriptions of the epidemiology of AA in the UK are lacking.

Retrospective study series using a large population-based cohort (5.2 million) from the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, exploring four themes AA epidemiology, mental health comorbidities, autoimmune/atopic associations and common infections.In the epidemiology theme, we will describe the incidence and point prevalence of AA overall and by age, sex and sociodemographic factors. Healthcare utilisation (primary care visits and secondary care referrals) and treatments for AA will also be assessed. In the mental health theme, we will explore the prevalence and incidence of mental health conditions (anxiety, depressive epiory tract infection, pneumonia, acute bronchitis, influenza, skin infection, urinary tract infection, genital infections, gastrointestinal infection, herpes simplex, herpes zoster, meningitis, COVID-19) in people with AA compared with matched controls.

The Health Research Authority decision tool classed this a study of usual practice, ethics approval was not required. Study approval was granted by the RCGP RSC Study Approval Committee. Results will be disseminated through peer-reviewed publications.

NCT04239521.

NCT04239521.Growing evidence demonstrates that circulating tumor DNA (ctDNA) minimal residual disease (MRD) following treatment for solid tumors predicts relapse. These results suggest that ctDNA MRD could identify candidates for adjuvant therapy and measure response to such treatment. Importantly, factors such as assay type, amount of ctDNA release, and technical and biological background can affect ctDNA MRD results. Furthermore, the clinical utility of ctDNA MRD for treatment personalization remains to be fully established. Here, we review the evidence supporting the value of ctDNA MRD in solid cancers and highlight key considerations in the application of this potentially transformative biomarker. SIGNIFICANCE ctDNA analysis enables detection of MRD and predicts relapse after definitive treatment for solid cancers, thereby promising to revolutionize personalization of adjuvant and consolidation therapies.The accumulation of sphingolipid species in the cell contributes to the development of obesity and neurological disease. However, the subcellular localization of sphingolipid-synthesizing enzymes is unclear, limiting the understanding of where and how these lipids accumulate inside the cell and why they are toxic. Here, we show that SPTLC2, a subunit of the serine palmitoyltransferase (SPT) complex, catalyzing the first step in de novo sphingolipid synthesis, localizes dually to the ER and the outer mitochondrial membrane. We demonstrate that mitochondrial SPTLC2 interacts and forms a complex in trans with the ER-localized SPT subunit SPTLC1. Loss of SPTLC2 prevents the synthesis of mitochondrial sphingolipids and protects from palmitate-induced mitochondrial toxicity, a process dependent on mitochondrial ceramides. Our results reveal the in trans assembly of an enzymatic complex at an organellar membrane contact site, providing novel insight into the localization of sphingolipid synthesis and the composition and function of ER-mitochondria contact sites.The role of G-quadruplex (G4) RNA structures is multifaceted and controversial. Here, we have used as a model the EBV-encoded EBNA1 and the Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded LANA1 mRNAs. We have compared the G4s in these two messages in terms of nucleolin binding, nuclear mRNA retention, and mRNA translation inhibition and their effects on immune evasion. The G4s in the EBNA1 message are clustered in one repeat sequence and the G4 ligand PhenDH2 prevents all G4-associated activities. The RNA G4s in the LANA1 message take part in similar multiple mRNA functions but are spread throughout the message. The different G4 activities depend on flanking coding and non-coding sequences and, interestingly, can be separated individually. Together, the results illustrate the multifunctional, dynamic and context-dependent nature of G4 RNAs and highlight the possibility to develop ligands targeting specific RNA G4 functions. The data also suggest a common multifunctional repertoire of viral G4 RNA activities for immune evasion.

The haptoglobin (Hp)2-2 phenotype (∼35-40% of people) is associated with increased oxidation and dysfunctional HDL in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL cholesterol and lower triglycerides have not reliably prevented cardiovascular disease in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial.

Cox proportional hazards regression models quantified the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n = 1,795) separately from those without (n = 3,201).

Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable adjusted hazard ratio 0.74 [95% CI 0.60-0.90] compared with no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16 [0.87-1.56]; P interaction = 0.009). see more Subgroup analyses revealed that this protective effect of fenofibrate against CAD events among the non-Hp2-2 phenotype group was pronounced in participants with severe dyslipidemia (P interaction = 0.01) and in males (P interaction = 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (P interaction = 0.002).

The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial.

The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial.

The capacity of general internal medicine (GIM) clinical teaching units has been strained by decreasing resident supply and increasing patient demand. The objective of our study was to compare the number of residents (supply) with the volume and duration of patient care activities (demand) to identify inefficiency.

Using the most recently available data from an academic teaching hospital in Toronto, Ontario, we identified each occurrence of a set of patient care activities that took place on the clinical teaching unit from 2015 to 2019. We completed a descriptive analysis of the frequencies of these activities and how the frequencies varied by hour, day, week, month and year. Patient care activities included admissions, rounds, responding to pages, meeting with patients and their families, patient transfers, discharges and responding to cardiac arrests. The estimated time to complete each task was based on the available data in our electronic medical record system and interviews with GIM physicians and trh or exceed 100%, particularly during daytime working hours.

Analyzing supply and demand on a GIM ward has allowed us to identify periods when supply and demand are not aligned and to demonstrate empirically the vulnerability of current staffing models. These data have the potential to inform and optimize scheduling on an internal medicine ward.

Analyzing supply and demand on a GIM ward has allowed us to identify periods when supply and demand are not aligned and to demonstrate empirically the vulnerability of current staffing models. These data have the potential to inform and optimize scheduling on an internal medicine ward.

Qualitative research is lacking on the mental well-being of adolescents during the COVID-19 pandemic. The aim of this study was to explore the feelings and emotions adolescents experienced during the first wave of the COVID-19 pandemic and the coping strategies they identified and employed to manage those emotions.

Participants living in Canada aged 13-19 years were recruited through social media platforms and youth-serving organizations. Qualitative data were gathered from 2 open-ended questions included in a youth-informed cross-sectional online survey "What feelings and emotions have you experienced around the pandemic?" and "What coping strategies have you used during the pandemic?" We collected data from June 2020 to September 2020. A summative content analysis was undertaken to analyze survey responses inductively.

A total of 1164 open-ended responses from Canadian adolescents (

= 851; mean age 15.6, standard deviation 1.7, yr) were analyzed. We identified 3 major themes within the category of fnd hobbies. The results have important implications for public health policy and practice during pandemic times, emphasizing the importance of accessible mental health resources for those experiencing psychological distress.

If untreated, Lyme disease can lead to long-term sequelae and post-treatment Lyme disease syndrome (PTLDS), resulting in reduced health-related quality of life. The objective of this study was to develop a microsimulation model to estimate the population-level health burden of Lyme disease in Ontario, Canada.

We developed a Lyme disease history model using microsimulation, simulating 100 000 people (mean age 37.6 yr, 51% female) from 2017 in Ontario over a lifetime risk of infection and time horizon. We extracted the sensitivity and specificity of the 2-tier testing recommended by the Canadian Public Health Laboratory Network, probabilities and health state utility values from the published literature and health administrative data. Our reported outcomes from our stochastic analysis include diagnosed cases of Lyme disease (stratified by stage), undiagnosed infections, sequelae, individuals with PTLDS and quality-adjusted life-years (QALYs) lost.

Our model estimated 333 (95% confidence interval [CI] 329-ence to understand the disease burden and lays the foundation to assess the cost-effectiveness of pharmaceutical and nonpharmaceutical interventions.

Asian Canadians and Asian Americans face COVID-19-related discrimination. The objective of this qualitative study was to explore the experiences of Asian health care workers dealing with discrimination, with a focus on racial micro-agressions, in Canada and the United States during the COVID-19 pandemic.

We adopted a qualitative descriptive approach. We used convenience and snowball sampling strategies to recruit participants. We conducted individual, in-depth semistructured interviews with Asian health care workers in Canada and the US via videoconferencing between May and September 2020. Eligible participants had to self-identify as Asian and be currently employed as a health care worker with at least 1 year of full-time employment. We used an inductive thematic approach to analyze the data.

Thirty participants were recruited. Fifteen (50%) were Canadians and 15 (50%) were Americans; there were 18 women (60%), 11 men (37%) and 1 nonbinary person. Most of the participants were aged 25-29 years (

= 16, 53%).