Molecular modelling of the GIR1 branching ribozyme gives new insight into evolution of structurally related ribozymes

Twin-ribozyme introns contain a branching ribozyme (GIR1) followed by a homing endonuclease (HE) encoding sequence embedded in a peripheral domain of a group I splicing ribozyme (GIR2). GIR1 catalyses the formation of a lariat with 3 nt in the loop, which caps the HE mRNA. GIR1 is structurally related to group I ribozymes raising the question about how two closely related ribozymes can carry out very different reactions. Modelling of GIR1 based on new biochemical and mutational data shows an extended substrate domain containing a GoU pair distinct from the nucleophilic residue that dock onto a catalytic core showing a different topology from that of group I ribozymes. The differences include a core J8/7 region that has been reduced and is complemented by residues from the pre-lariat fold. These findings provide the basis for an evolutionary mechanism that accounts for the change from group I splicing ribozyme to the branching GIR1 architecture. Such an evolutionary mechanism can be applied to other large RNAs such as the ribonuclease P

Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults

Importance: The prevalence and baseline risk factors of post-COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19. Objectives: To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors. Design, Setting, and Participants: This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. At the early convalescent stage and at 6-month follow-up, participants underwent a clinical examination; pulmonary, cardiac, and cognitive functional testing; immunological and organ injury biomarker analyses; and completion of a questionnaire. Participants were classified according to the World Health Organization case definition of PCC at follow-up. Association analyses of 78 potential risk factors were performed. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The point prevalence of PCC 6 months after RT-PCR testing in the SARS-CoV-2-positive and SARS-CoV-2-negative groups, and the risk difference with corresponding 95% CIs. Results: A total of 404 individuals testing positive for SARS-CoV-2 and 105 individuals testing negative were enrolled (194 male [38.1%]; 102 non-European [20.0%] ethnicity). A total of 22 of the SARS-CoV-2-positive and 4 of the SARS-CoV-2-negative individuals were lost to follow-up, and 16 SARS-CoV-2-negative individuals were excluded due to SARS-CoV-2 infection in the observational period. Hence, 382 SARS-CoV-2-positive participants (mean [SD] age, 18.0 [3.7] years; 152 male [39.8%]) and 85 SARS-CoV-2-negative participants (mean [SD] age, 17.7 [3.2] years; 31 male [36.5%]) could be evaluated. The point prevalence of PCC at 6 months was 48.5% in the SARS-CoV-2-positive group and 47.1% in the control group (risk difference, 1.5%; 95% CI, -10.2% to 13.1%). SARS-CoV-2 positivity was not associated with the development of PCC (relative risk [RR], 1.06; 95% CI, 0.83 to 1.37; final multivariable model utilizing modified Poisson regression). The main risk factor for PCC was symptom severity at baseline (RR, 1.41; 95% CI, 1.27-1.56). Low physical activity (RR, 0.96; 95% CI, 0.92-1.00) and loneliness (RR, 1.01; 95% CI, 1.00-1.02) were also associated, while biological markers were not. Symptom severity correlated with personality traits. Conclusions and Relevance: The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors. This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC

Type D personality is associated with increased metabolic syndrome prevalence and an unhealthy lifestyle in a cross-sectional Dutch community sample

<p>Abstract</p> <p>Background</p> <p>People with Type D-Distressed-personality have a general tendency towards increased negative affectivity (NA), while at the same time inhibiting these emotions in social situations (SI). Type D personality is associated with an increased risk of adverse outcomes in patients with cardiovascular disease. Whether Type D personality is a cardiovascular risk factor in healthy populations remains to be investigated. In the present study, the relations between Type D personality and classical cardiovascular risk factors, i.e. metabolic syndrome and lifestyle were investigated in a Dutch community sample.</p> <p>Methods</p> <p>In a cross-sectional study 1592 participants were included, aged 20-80 years. Metabolic syndrome was defined by self-report, following the International Diabetes Federation-IDF-guidelines including an increased waist circumference, dyslipidemia, hypertension, and diabetes. In addition lifestyle factors smoking, alcohol use, exercise and dietary habits were examined. Metabolic syndrome prevalence was stratified by Type D personality (a high score on both NA and SI), lifestyle and confounders age, gender, having a partner, higher education level, cardiac history, family history of cardiovascular disease.</p> <p>Results</p> <p>Metabolic syndrome was more prevalent in persons with a Type D personality (13% vs. 6%). Persons with Type D personality made poorer lifestyle choices, adhered less to the physical activity norm (OR = 1.5, 95%CI = 1.1-2.0, <it>p </it>= .02), had a less varied diet (OR = 0.50, 95%CI = 0.40-0.70, <it>p </it>< .0005), and were less likely to restrict their fat intake (OR = 0.70, 95%CI = 0.50-0.90, <it>p </it>= .01). Type D personality was related to a twofold increased risk of metabolic syndrome (OR = 2.2, 95%CI = 1.2-4.0, <it>p </it>= .011), independent of lifestyle factors and confounders.</p> <p>Conclusions</p> <p>Type D personality is related to an increased prevalence of metabolic syndrome and unhealthy lifestyle, which suggests both behavioral and biological vulnerability for development of cardiovascular disorders and diabetes.</p

Diabetes MILES – The Netherlands: rationale, design and sample characteristics of a national survey examining the psychosocial aspects of living with diabetes in Dutch adults

Background : As the number of people with diabetes is increasing rapidly worldwide, a more thorough understanding of the psychosocial aspects of living with this condition has become an important health care priority. While our knowledge has grown substantially over the past two decades with respect to the physical, emotional and social difficulties that people with diabetes may encounter, many important issues remain to be elucidated. Under the umbrella of the Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study International Collaborative, Diabetes MILES &ndash; The Netherlands aims to examine how Dutch adults with diabetes manage their condition and how it affects their lives. Topics of special interest in Diabetes MILES - The Netherlands include subtypes of depression, Type D personality, mindfulness, sleep and sexual functioning. Methods/design : Diabetes MILES &ndash; The Netherlands was designed as a national online observational study among adults with diabetes. In addition to a main set of self-report measures, the survey consisted of five complementary modules to which participants were allocated randomly. From September to October 2011, a total of 3,960 individuals with diabetes (40% type 1, 53% type 2) completed the battery of questionnaires covering a broad range of topics, including general health, self-management, emotional well-being and contact with health care providers. People with self-reported type 1 diabetes (specifically those on insulin pump therapy) were over-represented, as were those using insulin among respondents with self-reported type 2 diabetes. People from ethnic minorities were under-represented. The sex distribution was fairly equal in the total sample, participants spanned a broad age range (19&ndash;90 years), and diabetes duration ranged from recent diagnosis to living with the condition for over fifty years. Discussion : The Diabetes MILES Study enables detailed investigation of the psychosocial aspects of living with diabetes and an opportunity to put these findings in an international context. With several papers planned resulting from a pooled Australian-Dutch dataset and data collections planned in other countries, the Diabetes MILES Study International Collaborative will contribute substantially to identifying potentially unmet needs of those living with diabetes and to inform clinical research and care across the globe. <br /

Lung Ultrasound to Assess Pulmonary Congestion in Patients with Acute Exacerbation of COPD

Øyvind Johannessen,1,2 Fride Uthaug Reite,3 Rahul Bhatnagar,1,2 Tarjei Øvrebotten,1,2 Gunnar Einvik,1,3,&ast; Peder L Myhre1,2,&ast; 1Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 2Department of Cardiology, Akershus University Hospital, Lørenskog, Norway; 3Department of Pulmonary Medicine, Akershus University Hospital, Lørenskog, Norway&ast;These authors contributed equally to this workCorrespondence: Peder L Myhre, Department of Cardiology, Akershus University Hospital, Lørenskog, 1478, Norway, Tel +47 93025644, Email [email protected]: Heart failure (HF) often coexists with chronic obstructive pulmonary disease (COPD) and is associated with worse outcomes. We aimed to assess the feasibility of detecting vertical artifacts (B-lines) on lung ultrasound (LUS) to identify concurrent HF in patients hospitalized with acute exacerbation of COPD (AECOPD). Second, we wanted to assess the association between B-lines and the risk of rehospitalization for AECOPD or death.Patients and Methods: In a prospective cohort study, 123 patients with AECOPD underwent 8-zone bedside LUS within 24h after admission. A positive LUS was defined by ≥ 3 B-lines in ≥ 2 zones bilaterally. The ability to detect concurrent HF (adjudicated by a cardiologist committee) and association with events were evaluated by logistic- and Cox regression models.Results: Forty-eight of 123 patients with AECOPD (age 75± 9 years, 57[46%] men) had concurrent HF. Sixteen (13%) patients had positive LUS, and the prevalence of positive LUS was similar between patients with and without concurrent HF (8[17%] vs 8[11%], respectively, p=0.34). The number of B-lines was higher in concurrent HF: median 10(IQR 6– 16) vs 7(IQR 5– 12), p=0.03. The sensitivity and specificity for a positive LUS to detect concurrent HF were 17% and 89%, respectively. Positive LUS was not associated with rehospitalization and mortality: Adjusted HR: 0.93(0.49– 1.75), p=0.81.Conclusion: LUS did not detect concurrent HF or predict risk in patients with AECOPD.Keywords: chronic obstructive pulmonary disease, heart failure, lung ultrasound, acute exacerbations, pulmonary congestion, B-line

Impact of a dementia-friendly program on detection and management of patients with cognitive impairment and delirium in acute-care hospital units: a controlled clinical trial design

Background Frail older persons with cognitive impairment (CI) are at special risk of experiencing delirium during acute hospitalisation. The purpose of this study was to investigate whether a dementia-friendly hospital program contributes to improved detection and management of patients with CI and risk of delirium at an acute-care hospital in Norway. Furthermore, we aimed to explore whether the program affected the detection of delirium, pharmacological treatment, 30-day re-hospitalisation, 30-day mortality and institutionalisation afterwards. Methods This study was part of a larger quality improvement project aiming at developing and implementing a new program for early screening and management of patients with CI. This study, evaluating the program are designed as a controlled clinical trial with a historical control group. It was conducted at two different medical wards at a large acute-care hospital in Norway from September 2018 to December 2019. A total of 423 acute hospitalised patients 75 years of age or older were included in the study. Delirium screening and cognitive tests were recorded by research staff with the 4 ‘A’s Test (4AT) and the Confusion Assessment Measure (CAM), while demographic and medical information was recorded from the electronic medical records (EMR). Results Implementation of the dementia-friendly hospital program did not show any significant changes in the identification of patients with CI. However, the share of patients screened with 4AT within 24 h increased from 0% to 35.5% (P < .001). The proportion of the patients with CI identified by the clinical staff, who received measures to promote “dementia-friendly” care and reduce the risk for delirium increased by 32.2% (P < .001), compared to the control group. Furthermore, the number of patients with CI who were prescribed antipsychotic, hypnotic or sedative medications was reduced by 24.5% (P < .001). There were no differences in delirium detection, 30-day readmission or 30-day mortality. Conclusions A model for early screening and multifactorial non-pharmacological interventions for patients with CI and delirium may improve management of this patient group, and reduce prescriptions of antipsychotic, hypnotic and sedative medications. The implementation in clinical practice of early screening using quality improvement methodology deserves attention. Trial registration The protocol of this study was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System with the registration number: NCT04737733 and date of registration: 03/02/2021