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Skin Health and Disease Feb 2023Radiation-induced morphea (RIM) is a rare but recognized late complication of radiotherapy. It was first described in 1905, not long after the initial discovery of...
Radiation-induced morphea (RIM) is a rare but recognized late complication of radiotherapy. It was first described in 1905, not long after the initial discovery of X-rays by Roentgen. Characterized by the deposition of excess collagen in the dermis, it results in thickening of the skin. Its frequency is approximately 2 in 1000. We present a series of three cases involving patients receiving radiotherapy treatment for breast cancer, each of which subsequently developed RIM. Because of its rarity, RIM is often misdiagnosed as infection or metastatic disease. This can lead to delayed diagnosis and treatment, leading to poorer outcomes such as chronic pain issues. Early dermatological involvement and tissue sampling to examine histopathological features can avoid this, leading to better care and improved results. A variety of treatment options are available, ranging from topical to systemic, with early induction more likely to result in a positive response.
PubMed: 36751336
DOI: 10.1002/ski2.148 -
Nucleic Acids Research Feb 2023tRNAs are key partners in ribosome-dependent protein synthesis. This process is highly dependent on the fidelity of tRNA aminoacylation by aminoacyl-tRNA synthetases and... (Review)
Review
tRNAs are key partners in ribosome-dependent protein synthesis. This process is highly dependent on the fidelity of tRNA aminoacylation by aminoacyl-tRNA synthetases and relies primarily on sets of identities within tRNA molecules composed of determinants and antideterminants preventing mischarging by non-cognate synthetases. Such identity sets were discovered in the tRNAs of a few model organisms, and their properties were generalized as universal identity rules. Since then, the panel of identity elements governing the accuracy of tRNA aminoacylation has expanded considerably, but the increasing number of reported functional idiosyncrasies has led to some confusion. In parallel, the description of other processes involving tRNAs, often well beyond aminoacylation, has progressed considerably, greatly expanding their interactome and uncovering multiple novel identities on the same tRNA molecule. This review highlights key findings on the mechanistics and evolution of tRNA and tRNA-like identities. In addition, new methods and their results for searching sets of multiple identities on a single tRNA are discussed. Taken together, this knowledge shows that a comprehensive understanding of the functional role of individual and collective nucleotide identity sets in tRNA molecules is needed for medical, biotechnological and other applications.
Topics: Aminoacylation; Transfer RNA Aminoacylation; Amino Acyl-tRNA Synthetases; Biotechnology; RNA, Transfer
PubMed: 36744444
DOI: 10.1093/nar/gkad007 -
Indian Heart Journal 2023Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America,... (Clinical Trial)
Clinical Trial
BACKGROUND & OBJECTIVE
Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA trial demonstrated that primary prevention (PP) patients in these regions benefit from an ICD or a cardiac resynchronization therapy defibrillator (CRT-D). We aimed to compare the rate of device therapy and mortality among ischemic and non-ischemic cardiomyopathy (ICM and NICM) PP patients who met guideline indications for ICD therapy and had an ICD/CRT-D implanted.
METHODS
Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from the above-mentioned regions. All-cause mortality and device therapy were examined by cardiomyopathy (ICM vs NICM) and implantation status. Cox proportional hazards methods were used, adjusting for factors affecting mortality risk.
RESULTS
Of 1848 PP NICM patients, 1007 (54.5%) received ICD/CRT-D, while 303 of 581 (52.1%) PP ICM patients received an ICD/CRT-D. The all-cause mortality rate at 3 years for NICM patients with and without an ICD/CRT-D was 13.1% and 18.3%, respectively (HR 0.51, 95% CI 0.38-0.68, p < 0.001). Similarly, all-cause mortality at 3 years in ICM patients was 13.8% in those with a device and 19.9% in those without an ICD/CRT-D (HR 0.54, 95% CI 0.33-.0.88, p = 0.011). The time to first device therapy, time to first shock, and time to first antitachycardia pacing (ATP) therapy were not significantly different between groups (p ≥ 0.263).
CONCLUSIONS
In this large data set of patients with a guideline-based PP ICD indication, defibrillator device implantation conferred a significant mortality benefit in both NICM and ICM patients. The rate of appropriate device therapy was also similar in both groups.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT02099721.
Topics: Defibrillators, Implantable; Cardiomyopathies; Humans; India; Male; Female; Middle Aged; Aged; Proportional Hazards Models; Prospective Studies; Death, Sudden, Cardiac
PubMed: 36736459
DOI: 10.1016/j.ihj.2023.01.010 -
Faculty Reviews 2022For more than three decades, RNA has been known to be a relevant and attractive macromolecule to target but figuring out which RNA should be targeted and how remains... (Review)
Review
For more than three decades, RNA has been known to be a relevant and attractive macromolecule to target but figuring out which RNA should be targeted and how remains challenging. Recent years have seen the confluence of approaches for screening, drug optimization, and target validation that have led to the approval of a few RNA-targeting therapeutics for clinical applications. This focused perspective aims to highlight - but not exhaustively review - key factors accounting for these successes while pointing at crucial aspects worth considering for further breakthroughs.
PubMed: 36644293
DOI: 10.12703/r/11-39 -
BMC Medical Education Jan 2023There is increasing recognition of including social determinants of health (SDOH) in teaching for future doctors. However, the educational methods and the extent of... (Review)
Review
BACKGROUND
There is increasing recognition of including social determinants of health (SDOH) in teaching for future doctors. However, the educational methods and the extent of integration into the curriculum vary considerably-this scoping review is aimed at how SDOH has been introduced into medical schools' curricula.
METHODS
A systematic search was performed of six electronic databases, including PubMed, Education Source, Scopus, OVID (Medline), APA Psych Info, and ERIC. Articles were excluded if they did not cover the SDOH curriculum for medical students; were based on service-learning rather than didactic content; were pilot courses, or were not in English, leaving eight articles in the final study.
RESULTS
The initial search yielded 654 articles after removing duplicates. In the first screening step, 588 articles were excluded after applying inclusion and exclusion criteria and quality assessment; we examined 66 articles, a total of eight included in the study. There was considerable heterogeneity in the content, structure and duration of SDOH curricula. Of the eight included studies, six were in the United States(U.S.), one in the United Kingdom (U.K.) and one in Israel. Four main conceptual frameworks were invoked: the U.S. Healthy People 2020, two World Health Organisation frameworks (The Life Course and the Michael Marmot's Social Determinants of Health), and the National Academic of Science, Engineering, and Medicine's (Framework For educating Health Professionals to Address the Social Determinants of Health). In general, programs that lasted longer appeared to perform better than shorter-duration programmes. Students favoured interactive, experiential-learning teaching methods over the traditional classroom-based teaching methods.
CONCLUSION
The incorporation of well-structured SDOH curricula capturing both local specification and a global framework, combined with a combination of traditional and interactive teaching methods over extended periods, may be helpful in steps for creating lifelong learners and socially accountable medical school education.
Topics: Humans; Social Determinants of Health; Curriculum; Education, Medical; Problem-Based Learning; Students, Medical
PubMed: 36631816
DOI: 10.1186/s12909-022-03899-2 -
Globalization and Health Dec 2022The vast investments that have been made in recent decades in new medicines, vaccines, and technologies will only lead to improvements in health if there are appropriate...
BACKGROUND
The vast investments that have been made in recent decades in new medicines, vaccines, and technologies will only lead to improvements in health if there are appropriate and well-functioning health systems to make use of them. However, despite the growing acceptance by major global donors of the importance of health systems, there is an enthusiasm gap when it comes to disbursing funds needed to understand the intricacies of how, why and when these systems deliver effective interventions. To understand the reasons behind this, we open up the black box of donor decision-making vis-à-vis Health Policy and Systems Research (HPSR) financing: what are the organizational processes behind the support for HPSR, and what are the barriers to increasing engagement?
METHODS
We conducted 27 semi-structured interviews with staff of major global health funders, asking them about four key issues: motivations for HPSR financing; priorities in HPSR financing; barriers for increasing HPSR allocations; and challenges or opportunities for the future. We transcribed the interviews and manually coded responses.
RESULTS
Our findings point to the growing appreciation that funders have of HPSR, even though it is often still seen as an 'afterthought' to larger programmatic interventions. In identifying barriers to funding HPSR, our informants emphasised the perceived lack of mandate and capacities of their organizations. For most funding organisations, a major barrier was that their leadership often voiced scepticism about HPSR's long time horizons and limited ability to quantify results.
CONCLUSION
Meeting contemporary health challenges requires strong and effective health systems. By allocating more resources to HPSR, global donors can improve the quality of their interventions, and also contribute to building up a stock of knowledge that domestic policymakers and other funders can draw on to develop better targeted programmes and policies.
Topics: Humans; Health Policy; Health Services Research; Government Programs; Financial Management; Investments
PubMed: 36564847
DOI: 10.1186/s12992-022-00896-4 -
Health Policy and Planning Mar 2023Health policy and systems research (HPSR) is a neglected area in global health financing. Despite repeated calls for greater investment, it seems that there has been... (Review)
Review
Health policy and systems research (HPSR) is a neglected area in global health financing. Despite repeated calls for greater investment, it seems that there has been little growth. We analysed trends in reported funding and activity between 2015 and 2021 using a novel real-time source of global health data, the Devex.com database, the world's largest source of funding opportunities related to international development. We performed a systematic search of the Devex.com database for HPSR-related terms with a focus on low- and middle-income countries. We included 'programs', 'tenders & grants' and 'contract awards', covering all call statuses (open, closed or forecast). Such funding opportunities were included if they were related specifically to HPSR funding or had an HPSR component; pure biomedical funding was excluded. Our findings reveal a relative neglect of HPSR, as only ∼2% of all global health funding calls included a discernible HPSR component. Despite increases in funding calls until 2019, this situation reversed in 2020, likely reflecting the redirection of resources to rapid assessments of the impacts of the coronavirus disease 2019 (COVID-19) pandemic. Most identified projects represented small-scale opportunities-commonly for consultancies or technical assistance. To the extent that new data were generated, these projects were either tied to a specific large intervention or were narrow in scope to meet a specific challenge-with many examples informing policy responses to the Covid-19 pandemic. Nearly half of advertised funding opportunities were multi-country projects, usually addressing global policy priorities like health systems strengthening or development of coordinated public health policies at a regional level. The Covid-19 pandemic has shown why investing in HPSR is more important than ever to enable the delivery of effective health interventions and avoid costly implementation failures. The evidence presented here highlights the need to scale up efforts to convince global health funders to institutionalize the inclusion of HPSR components in all funding calls.
Topics: Humans; Pandemics; Health Services Research; COVID-19; Health Policy; Financing, Organized; Global Health
PubMed: 36546732
DOI: 10.1093/heapol/czac109 -
Radiology Apr 2023Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after...
Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, fatigue) underwent same-day EID and PCD CT between April 2022 and June 2022. The 1.0-mm EID CT images and, subsequently, 1.0-, 0.4-, and 0.2-mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality were evaluated using a five-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNRs). Results Twenty participants (mean age, 54 years ± 16 [SD]; 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants, with a median involvement of 10% of lung volume [IQR, 0%-45%] and 3.5 lobes [IQR, 0-5]. Ground-glass opacities and linear bands (10 of 20 participants [50%] for both) were the most frequent findings at EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, with the most common being bronchiectasis (10 of 20 [50%]). Subjective image quality was improved for 1.0-mm PCD versus 1.0-mm EID CT images (median, 1; IQR, 1-2; < .001) and 0.4-mm versus 1.0-mm PCD CT images (median, 1; IQR, 1-1; < .001) but not for 0.4-mm versus 0.2-mm PCD CT images (median, 0; IQR, 0-0.5; = .26). PCD CT delivered higher lung SNR versus EID CT for 1.0-mm images (mean difference, 0.53 ± 0.96; = .03) but lower SNR for 0.4-mm versus 1.0-mm images and 0.2-mm vs 0.4-mm images (-1.52 ± 0.68 [ < .001] and -1.15 ± 0.43 [ < .001], respectively). Conclusion Photon-counting detector CT outperformed energy-integrating detector CT in the visualization of subtle post-COVID-19 lung abnormalities and image quality. © RSNA, 2023
Topics: Male; Adult; Humans; Middle Aged; Prospective Studies; Phantoms, Imaging; Photons; COVID-19; Tomography, X-Ray Computed; Lung
PubMed: 36445225
DOI: 10.1148/radiol.222087 -
International Journal of Molecular... Nov 2022Allocation of morbidly obese patients to either conservative therapy options-such as lifestyle intervention and/or low-calorie diet (LCD)-or to bariatric...
Allocation of morbidly obese patients to either conservative therapy options-such as lifestyle intervention and/or low-calorie diet (LCD)-or to bariatric surgery-preferably sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB)-represents a crucial decision in order to obtain sustainable metabolic improvement and weight loss. The present study encompasses 160 severely obese patients, 81 of whom participated in an LCD program, whereas 79 underwent RYGB surgery. The post-interventional dynamics of physiologically relevant adipokines and hepatokines (ANGPTL4, CCL5, GDF15, GPNMB, IGFBP6), as well as their correlation with fat mass reduction and improvement of liver fibrosis, were analyzed. Systemic GDF15 was characterized as an excellent predictive marker for hepatic fibrosis as well as type 2 diabetes mellitus. Of note, baseline GDF15 serum concentrations were positively correlated with NFS and HbA1c levels after correction for BMI, suggesting GDF15 as a BMI-independent marker of hepatic fibrosis and T2D in obese individuals. Specific GDF15 cut-off values for both diseases were calculated. Overall, the present data demonstrate that circulating levels of specific adipokines and hepatokines are regulated with therapy-induced fat loss and metabolic improvement and might, therefore, serve as biomarkers for the success of obesity therapy strategies.
Topics: Humans; Obesity, Morbid; Adipokines; Diabetes Mellitus, Type 2; Gastric Bypass; Biomarkers; Liver Cirrhosis; Membrane Glycoproteins
PubMed: 36430499
DOI: 10.3390/ijms232214020 -
International Journal of Molecular... Nov 2022Recent evidence indicates that the HIV-1 Integrase (IN) binds the viral genomic RNA (gRNA), playing a critical role in the morphogenesis of the viral particle and in the...
Recent evidence indicates that the HIV-1 Integrase (IN) binds the viral genomic RNA (gRNA), playing a critical role in the morphogenesis of the viral particle and in the stability of the gRNA once in the host cell. By combining biophysical, molecular biology, and biochemical approaches, we found that the 18-residues flexible C-terminal tail of IN acts as a sensor of the peculiar apical structure of the trans-activation response element RNA (TAR), interacting with its hexaloop. We show that the binding of the whole IN C-terminal domain modifies TAR structure, exposing critical nucleotides. These modifications favour the subsequent binding of the HIV transcriptional trans-activator Tat to TAR, finally displacing IN from TAR. Based on these results, we propose that IN assists the binding of Tat to TAR RNA. This working model provides a mechanistic sketch accounting for the emerging role of IN in the early stages of proviral transcription and could help in the design of anti-HIV-1 therapeutics against this new target of the viral infectious cycle.
Topics: tat Gene Products, Human Immunodeficiency Virus; HIV Integrase; RNA, Viral; Transcription Factors
PubMed: 36430221
DOI: 10.3390/ijms232213742