Systemic sclerosis (SSc) is a heterogeneous disease characterized by autoimmunity, vasculopathy, and fibrosis which affects the skin and internal organs. One key aspect of SSc vasculopathy is ...pulmonary arterial hypertension (SSc-PAH) which represents a leading cause of morbidity and mortality in patients with SSc. The pathogenesis of pulmonary hypertension is complex, with multiple vascular cell types, inflammation, and intracellular signaling pathways contributing to vascular pathology and remodeling. In this review, we focus on shared molecular features of pulmonary hypertension and those which make SSc-PAH a unique entity. We highlight advances in the understanding of the clinical and translational science pertinent to this disease. We first review clinical presentations and phenotypes, pathology, and novel biomarkers, and then highlight relevant animal models, key cellular and molecular pathways in pathogenesis, and explore emerging treatment strategies in SSc-PAH.
Background
Twitter has been shown to expand the audience and impact of material discussed at medical conferences, however, this phenomenon has not been analysed at the Royal Australasian College of ...Surgeons Annual Scientific Congress. The purpose of this study is to document the amount of Twitter activity at the Annual Scientific Congress, and to describe the way delegates use Twitter.
Methods
The number of tweets, retweets and contributors from the 2015 to 2018 congresses were determined using the Twitter advanced search function. Tweets were categorized broadly as academic, social or promotional. Union Metrics, an online software, was used to calculate estimates of impact including impressions and reach at the 2018 congress. Popular topics of discussion at all congresses were defined and counted.
Results
Twelve thousand five hundred and eight‐six tweets were created with the official hashtag at the time of the four congresses. Activity increased over time except in the number of original tweets between the 2016 and 2018 congresses. Sixty‐six percent of the tweets were directly related to congress content, and 23% were social in nature. At the 2018 congress, 16–34% of contributors were matched with a congress delegate.
Conclusion
The tweets analysed were mainly informative. Twitter expanded the audience for material discussed at the Annual Scientific Congresses, and the amount of Twitter activity generally increased. It is in the interest of conference organizers to encourage and regulate Twitter use for maximum effectiveness because it is a powerful tool and use is likely to continue increasing in future.
Twitter is increasingly being used to document academic congresses. This study demonstrates how Twitter use is growing at the Royal Australasian College of Surgeons Annual Scientific Congress, and the reasons surgeons publish content to Twitter.
Research examining the longer term influences of child care on children's development has expanded in recent years, but few studies have considered low-income children's experiences in community care ...arrangements. Using data from the Three-City Study (N = 349), the present investigation examines the influences of child care quality, extent and type on low-income children's development of behavior problems during middle childhood (7-11 years old). Higher levels of child care quality were linked to moderate reductions in externalizing behavior problems. High-quality child care was especially protective against the development of behavior problems for boys and African American children. Child care type and the extent of care that children experienced were generally unrelated to behavior problems in middle childhood.
Summary
MicroRNAs (miRNAs) are small non‐coding RNA molecules that play a crucial role in gene regulation. They are produced through an enzyme‐guided process called dicing and have an asymmetrical ...structure with two nucleotide overhangs at the 3′ ends. Artificial microRNAs (amiRNAs or amiRs) are designed to mimic the structure of miRNAs and can be used to silence specific genes of interest. Traditionally, amiRNAs are designed based on an endogenous miRNA precursor with certain mismatches at specific positions to increase their efficiency. In this study, the authors modified the highly expressed miR168a in Arabidopsis thaliana by replacing the single miR168 stem‐loop/duplex with tandem asymmetrical amiRNA duplexes that follow the statistical rules of miRNA secondary structures. These tandem amiRNA duplexes, called “two‐hit” amiRNAs, were shown to have a higher efficiency in silencing GFP and endogenous PDS reporter genes compared to traditional “one‐hit” amiRNAs. The authors also demonstrated the effectiveness of “two‐hit” amiRNAs in silencing genes involved in miRNA, tasiRNA, and hormone signalling pathways, individually or in families. Importantly, “two‐hit” amiRNAs were also able to over‐express endogenous miRNAs for their functions. The authors compare “two‐hit” amiRNA technology with CRISPR/Cas9 and provide a web‐based amiRNA designer for easy design and wide application in plants and even animals.
Proper home medication management plays a role in improving medication adherence, preserving drug efficacy and ensuring safe medication practices, which is crucial to establish positive treatment ...outcomes. However, no published studies are available on home medication management among psychiatric patients. The study aimed to identify home medication management problems among psychiatric patients in Malaysia and to examine the associations of inappropriate medication storage and lack of a medication administration schedule with sociodemographic factors, disease insight, number of medications and type of home care pharmacy services (HCPS).
This multicentre cross-sectional study was conducted among psychiatric patients using HCPS in six government hospitals in western Malaysia. Data were extracted from the HCPS form used for each visit as per the protocol published by the Pharmaceutical Services Division, Ministry of Health Malaysia. A minimum sample size of 169 was needed. Proportional random sampling was applied. The associations of inappropriate medication storage and lack of medication administration schedule with study parameters were analysed using multiple logistic regressions.
A total of 205 home visits were conducted with 229 home medication management problems identified; inappropriate medication storage and lack of medication administration schedule topped the list. Inappropriate medication storage was significantly associated with low income AOR = 4.34 (95% CI 1.17:15.98), p = 0.027, alcohol consumption AOR = 14.26 (95% CI 1.82:111.38), p = 0.011, poor insight AOR = 2.34 (95% CI 1.08:5.06), p = 0.030 and part-time HCPS AOR = 2.60 (95% CI 1.20:5.67), p = 0.016. Lack of administration schedule was significantly associated with low income AOR = 6.90 (95% CI 1.46:32.48), p = 0.014, smoking AOR = 2.43 (95% CI 1.20:4.92), p = 0.013, poor insight AOR = 5.32 (95% CI 2.45:11.56), p < 0.05 and part-time HCPS AOR = 2.96 (95% CI 1.42:6.15), p = 0.004.
Inappropriate medication storage and a lack of a medication administration schedule are common among psychiatric patients. The study also highlighted the potential of HCPS to improve disease insight and home medication management among psychiatric patients if the service is utilized fully.
A primary aim of the Chicago School Readiness Project was to improve teachers’ emotionally supportive classroom practices in Head Start-funded preschool settings. Using a clustered randomized ...controlled trial (RCT) design, the Chicago School Readiness Project randomly assigned a treatment versus control condition to 18 Head Start sites, which included 35 classrooms led by 94 teachers who served 602 children. Teachers in the treatment condition were invited to participate in behavior management training and their classrooms were visited weekly by mental health consultants who “coached” teachers as they implemented behavior management strategies. Estimation of hierarchical linear models revealed that the multi-component intervention provided statistically significant benefits: Head Start classrooms randomized to the treatment condition were found to have statistically significantly higher levels of positive classroom climate, teacher sensitivity, and behavior management than were classrooms in the control condition (with effect sizes ranging from
d
=
0.52 to 0.89). Discussion of these findings reflects on policy implications and future research.
The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures ...derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated 16 of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.
Abstract
Background
Molding competent clinicians capable of applying ethics principles in their practice is a challenging task, compounded by wide variations in the teaching and assessment of ethics ...in the postgraduate setting. Despite these differences, ethics training programs should recognise that the transition from medical students to healthcare professionals entails a longitudinal process where ethics knowledge, skills and identity continue to build and deepen over time with clinical exposure.
A systematic scoping review is proposed to analyse current postgraduate medical ethics training and assessment programs in peer-reviewed literature to guide the development of a local physician training curriculum.
Methods
With a constructivist perspective and relativist lens, this systematic scoping review on postgraduate medical ethics training and assessment will adopt the Systematic Evidence Based Approach (SEBA) to create a transparent and reproducible review.
Results
The first search involving the teaching of ethics yielded 7669 abstracts with 573 full text articles evaluated and 66 articles included. The second search involving the assessment of ethics identified 9919 abstracts with 333 full text articles reviewed and 29 articles included. The themes identified from the two searches were the goals and objectives, content, pedagogy, enabling and limiting factors of teaching ethics and assessment modalities used. Despite inherent disparities in ethics training programs, they provide a platform for learners to apply knowledge, translating it to skill and eventually becoming part of the identity of the learner. Illustrating the longitudinal nature of ethics training, the spiral curriculum seamlessly integrates and fortifies prevailing ethical knowledge acquired in medical school with the layering of new specialty, clinical and research specific content in professional practice. Various assessment methods are employed with special mention of portfolios as a longitudinal assessment modality that showcase the impact of ethics training on the development of professional identity formation (PIF).
Conclusions
Our systematic scoping review has elicited key learning points in the teaching and assessment of ethics in the postgraduate setting. However, more research needs to be done on establishing Entrustable Professional Activities (EPA)s in ethics, with further exploration of the use of portfolios and key factors influencing its design, implementation and assessment of PIF and micro-credentialling in ethics practice.
Introduction
Primary hyperparathyroidism (PHPT) results in increased bone turnover, resulting in bone mineral density (BMD) reduction and a predisposition towards fractures. Parathyroidectomy (PTX) ...is the only definitive cure.
Objective
The primary goals of this study were to investigate the impact of PTX on BMD in patients with PHPT and to identify factors associated with post-operative BMD improvement using a multivariate model.
Methods
Between 1999 and 2010, a total of 757 patients underwent PTX for treatment of PHPT; 123 patients had both a pre- and a post-operative dual-energy X-ray absorptiometry (DEXA) scan. A prospective database was queried to obtain information about patient demographics, medications, comorbidities, and pre- and post-operative laboratory values. A Cox regression model was used to stratify patients and to identify factors that independently predict BMD response following PTX in this patient population.
Results
Overall, mean percent change in BMD was +12.31 % at the spine, +8.9 % at the femoral neck (FN), and +8.5 % at the hip, with a mean follow-up of 2.3 ± 1.5 years. A total of 101 (82.1 %) patients had BMD improvement at their worst pre-operative site. In patients who improved, 69.9 % (
n
= 86) had >5 % increase. Factors associated with BMD improvement at the worst pre-operative site were as follows: male gender (hazard ratio HR 2.29; 95 % confidence interval CI 1.54–4.21); pre-operative BMD with T-score less than −2.0 (HR 1.89; 95 % CI 1.11–2.39); age <55 years (HR 1.74; 95 % CI 1.14–2.25); BMD DEXA scan at >2.5 years post-operatively (HR 1.71; 95 % CI 1.09–2.17); history of previous fracture (HR 1.24; 95 % CI 1.05–1.92); and private insurance (HR 1.18; 95 % CI 1.06–2.1). The use of bisphosphonates, estrogens, vitamin D supplementation, or tobacco; obesity; history of previous PTX, serum calcium or parathyroid hormone levels were not independently associated with post-operative BMD improvement.
Conclusion
Osteoporosis is one of the established National Institutes of Health criteria for PTX in asymptomatic patients with PHPT, but BMD improvement is not consistently seen during the post-operative period. Gender, age, more severe pre-operative bone disease, and insurance status were all predictors for greater BMD improvement following PTX. Further studies with a rigorous post-operative BMD regimen are needed in order to validate these results.