Exercise Tolerance Improves After Pulmonary Rehabilitation in Pulmonary Hypertension Patients

Pulmonary rehabilitation (PR) is part of the recommended management plan of pulmonary hypertension (PHTN) and is important to better quality of life and exercise tolerance. This study aimed at determining effectiveness of PR on exercise capacity. Retrospective chart analysis was conducted on patients referred to our PHTN clinic for PR. Patients who had PHTN diagnosed on right heart catheterization (defined by mean pulmonary artery pressure\u3e25 mmHg) and completed a standardized 12-week PR program were considered for the study. Patients’ baseline exercise tolerance was recorded as speed attainable on a treadmill and duration of exercise in minutes. Demographics, age, sex, and oxygen use were obtained from chart review. Eighteen PHTN patients (5 male, 13 female; mean age 67.7±11.6 years) were considered for the study (six World Health Organization [WHO] group 1 pulmonary arterial hypertension [33.33%], eight WHO group III PHTH [44.44%], two WHO group IV and two WHO V PHTN [11.11%]). Treadmill speed improved following rehabilitation (1.3 mph [interquartile range {IQR}, 1.0–1.8 mph] to 2.2 mph [IQR, 1.3–2.8 mph]; P\u3c0.0001, Wilcoxon signed rank test). Median exercise time improved (27 min (IQR, 22–30 min) to 30 min (IQR, 24–30 min); not significant. Improvement was defined only as an increase in speed or duration, or both. Sixteen of 18 participants improved (88.9% [95% exact binomial confidence interval, 65.3%–98.6%). Patients with PHTN benefit from a structured PR program to improve their exercise capacity and should be enrolled in PR programs as part of their management

Effects of pulmonary rehabilitation on Fatigue Severity Scale in patients with lung disease

Wstęp: Z męczenie jest dobrze znanym objawem zaawansowanej choroby płuc. Ma ona znaczący wpływ na jakość życia i zdrowie psychiczne pacjenta, dlatego wielu pacjentów w ramach terapii przechodzi rehabilitację oddechową. Aby stworzyć nowe ukierunkowane programy rehabilitacyjne bardzo istotne jest zrozumienie wpływu rehabilitacji oddechowej na nasilenie duszności u tych chorych.Celem pracy jest ocena wpływu rehabilitacji oddechowej na nasilenie zmęczenia mierzonego za pomocą Fatigue Severity Scale (FSS) u pacjentów z zaawansowaną chorobą płuc.Materiał i metody: Pacjenci zakwalifikowani do standardowego 6-tygodniowego programu rehabilitacyjnego byli proszeni o dokładne wypełnienie 2 ankiet przed rehabilitacją i po jej zakończeniu: ankiety FSS, która jest cennym narzędziem pozwalającym na ocenę zmęczenia pod kątem potrzeby interwencji medycznej, oraz ankiety Geriatric Depression Scale (GDS), która jest narzędziem używanym do oceny nasilenia depresji przez samych pacjentów. Dane przeanalizowano za pomocą programu Statistical Analysis System (SAS). Z mienne wartości FSS oceniono przy użyciu testu Wilcoxona dla par obserwacji. Wartości p < 0,05 uznano za istotne statystycznie.Wyniki: Do badania włączono 21 pacjentów (12 kobiet i 9 mężczyzn, średnia wieku 64,3 ± 11,2 roku). Wyniki FSS przed rehabilitacją wynosiły od 1,6 do 6,7 (średni wynik na poziomie 4,6 ± 1,7), a po rehabilitacji od 1,0 do 6,2 (średni wynik na poziomie 3,9 ± 1,6). Mediana FSS przed rehabilitacją wynosiła 5,3 (przedział międzykwartylowy; Q1–Q3: 3,0–6,1), po rehabilitacji wyniosła 3,9 (przedział międzykwartylowy; Q1–Q3: 2,6–5,1). Wykazano istotnie statystycznie niższy wynik w FSS po zakończeniu programu rehabilitacji oddechowej (p < 0,0208; test Wilcoxona dla par obserwacji). Wykazano również niższy wynik w GDS po rehabilitacji, ale nie był on istotny statystycznie (średnia przed rehabilitacją: 5,5 ± 3,6; średnia po rehabilitacji: 4,2 ± 2,9). Z miany w GDS korelowały ze zmianami w FSS (współczynnik korelacji rang Spearmana 0,525, p < 0,0146).Wnioski: U chorych z zaawansowaną chorobą płuc nasilenie zmęczenia można przedstawić za pomocą mierzalnych danych. U pacjentów, którzy przeszli program rehabilitacji oddechowej, stwierdzono istotną poprawę w postaci zmniejszenia nasilenia zmęczenia. Potrzebne są dalsze badania, aby oceniać nowe metody leczenia, które pozwolą zmniejszyć dolegliwości towarzyszące zaawansowanym chorobom płuc.Introduction: Fatigue is a known symptom of advanced lung disease and impacts quality of life and psychological health. Many of these patients undergo pulmonary rehabilitation as part of their therapy. Understanding the effect of pulmonary rehabilitation on fatigue in these patients is important, as one may be able to design more focused rehabilitation programs. The aim of this study is to evaluate the effect of pulmonary rehabilitation on fatigue as measured by the Fatigue Severity Scale (FSS) in patients with advanced lung disease.Material and methods: Patients were enrolled in a standardized 6 week pulmonary rehabilitation program. They were asked to complete questionnaires to evaluate their self-reported fatigue (FSS), and depression as measured by Geriatric Depression Scale (GDS). The GDS is a self-reported assessment tool used to identify depression in patients. The FSS is a validated instrument that indicates a perception of fatigue that might require medical intervention. Participants completed questionnaires both at baseline and after completing the standardized pulmonary rehabilitation program. Data was analyzed in Statistical Analysis System (SAS). The change in FSS was evaluated using the Wilcoxon signed-rank test. P-values < 0.05 were considered statistically significant.Results: 21 patients (12 females; 9 males; mean age 64.3 ± 11.2 yrs) were considered for the study. Pre-pulmonary rehabilitation FSS scores ranged from 1.6 to 6.7 (mean score of 4.6 ± 1.7). Post pulmonary rehabilitation FSS scores ranged 1.0 to 6.2 (mean score of 3.9 ± 1.6). The median pre-rehabilitation FSS was 5.3 (inter quartile range; Q1–Q3: 3.0–6.1), and median post rehabilitation FSS was 3.9 (inter quartile range; Q1–Q3: 2.6–5.1). There was a significant decrease in FSS scores after completing pulmonary rehabilitation program (p < 0.0208). There was a decrease in GDS (pre-rehabilitation, mean: 5.5 ± 3.6; post-rehabilitation, mean: 4.2 ± 2.9), but this decrease was not statistically significant. The change in GDS correlated with the change in FSS (Spearman Correlation Coefficient 0.525, p < 0.0146).Conclusions: Patients with advanced lung disease reported a measurable component of fatigue. Participating in pulmonary rehabilitation resulted in significant improvement in patient’s self-reported fatigue severity. Further studies are necessary to evaluate and design interventions to improve fatigue in in the setting of advanced lung disease

Transformational teaching, self-presentation motives, and identity in adolescent female physical education

This study examined whether teachers’ use of transformational teaching behaviors, as perceived by adolescent girls, in physical education would predict girls’ moderate to vigorous physical activity via mediated effects of physical activity self-presentation motives, physical activity identity, and physical education class engagement. Self-report data were acquired from 273 Scottish high school girls in Grades S1–S3 (the equivalent of Grades 7–9 in North America) at 2 time points separated by 1 week. Significant predictive pathways were found from transformational teaching to girls’ moderate to vigorous physical activity via mediated effects of acquisitive self-presentation motives and physical activity identity. This preliminary study provides a novel contribution to the research area by showing how previously unrelated psychosocial constructs work together to predict adolescent girls’ moderate to vigorous physical activity. Results are discussed in relation to existing literature and future research directions

The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo

SummaryResearch over the past decade has suggested important roles for pseudogenes in physiology and disease. In vitro experiments demonstrated that pseudogenes contribute to cell transformation through several mechanisms. However, in vivo evidence for a causal role of pseudogenes in cancer development is lacking. Here, we report that mice engineered to overexpress either the full-length murine B-Raf pseudogene Braf-rs1 or its pseudo “CDS” or “3′ UTR” develop an aggressive malignancy resembling human diffuse large B cell lymphoma. We show that Braf-rs1 and its human ortholog, BRAFP1, elicit their oncogenic activity, at least in part, as competitive endogenous RNAs (ceRNAs) that elevate BRAF expression and MAPK activation in vitro and in vivo. Notably, we find that transcriptional or genomic aberrations of BRAFP1 occur frequently in multiple human cancers, including B cell lymphomas. Our engineered mouse models demonstrate the oncogenic potential of pseudogenes and indicate that ceRNA-mediated microRNA sequestration may contribute to the development of cancer

Health financing policies during the COVID-19 pandemic and implications for universal health care: a case study of 15 countries

Background The COVID-19 pandemic was a health emergency requiring rapid scal resource mobilisation to support national responses. The use of e ective health nancing mechanisms and policies, or lack thereof, a ected the impact of the pandemic on the population, particularly vulnerable groups and individuals. We provide an overview and illustrative examples of health nancing policies adopted in 15 countries during the pandemic, develop a framework for resilient health nancing, and use this pandemic to argue a case to move towards universal health coverage (UHC). Methods In this case study, we examined the national health nancing policy responses of 15 countries, which were purposefully selected countries to represent all WHO regions and have a range of income levels, UHC index scores, and health system typologies. We did a systematic literature review of peer-reviewed articles, policy documents, technical reports, and publicly available data on policy measures undertaken in response to the pandemic and complemented the data obtained with 61 in-depth interviews with health systems and health nancing experts. We did a thematic analysis of our data and organised key themes into a conceptual framework for resilient health nancing. Findings Resilient health nancing for health emergencies is characterised by two main phases: (1) absorb and recover, where health systems are required to absorb the initial and subsequent shocks brought about by the pandemic and restabilise from them; and (2) sustain, where health systems need to expand and maintain scal space for health to move towards UHC while building on resilient health nancing structures that can better prepare health systems for future health emergencies. We observed that ve key nancing policies were implemented across the countries— namely, use of extra-budgetary funds for a swift initial response, repurposing of existing funds, e cient fund disbursement mechanisms to ensure rapid channelisation to the intended personnel and general population, mobilisation of the private sector to mitigate the gaps in public settings, and expansion of service coverage to enhance the protection of vulnerable groups. Accountability and monitoring are needed at every stage to ensure e cient and accountable movement and use of funds, which can be achieved through strong governance and coordination, information technology, and community engagement. Interpretation Our ndings suggest that health systems need to leverage the COVID-19 pandemic as a window of opportunity to make health nancing policies robust and need to politically commit to public nancing mechanisms that work to prepare for future emergencies and as a lever for UHC.We thank the management team of the Bill & Melinda Gates Foundation and the Saw Swee Hock School of Public Health (National University of Singapore, Singapore) for all the administrative support given. This research was funded by the Bill & Melinda Gates Foundation (Investment ID INV-005598)

Multisite Phosphorylation Provides an Effective and Flexible Mechanism for Switch-Like Protein Degradation

Phosphorylation-triggered degradation is a common strategy for elimination of regulatory proteins in many important cell signaling processes. Interesting examples include cyclin-dependent kinase inhibitors such as p27 in human and Sic1 in yeast, which play crucial roles during the G1/S transition in the cell cycle. In this work, we have modeled and analyzed the dynamics of multisite-phosphorylation-triggered protein degradation systematically. Inspired by experimental observations on the Sic1 protein and a previous intriguing theoretical conjecture, we develop a model to examine in detail the degradation dynamics of a protein featuring multiple phosphorylation sites and a threshold site number for elimination in response to a kinase signal. Our model explains the role of multiple phosphorylation sites, compared to a single site, in the regulation of protein degradation. A single-site protein cannot convert a graded input of kinase increase to much sharper output, whereas multisite phosphorylation is capable of generating a highly switch-like temporal profile of the substrate protein with two characteristics: a temporal threshold and rapid decrease beyond the threshold. We introduce a measure termed temporal response coefficient to quantify the extent to which a response in the time domain is switch-like and further investigate how this property is determined by various factors including the kinase input, the total number of sites, the threshold site number for elimination, the order of phosphorylation, the kinetic parameters, and site preference. Some interesting and experimentally verifiable predictions include that the non-degradable fraction of the substrate protein exhibits a more switch-like temporal profile; a sequential system is more switch-like, while a random system has the advantage of increased robustness; all the parameters, including the total number of sites, the threshold site number for elimination and the kinetic parameters synergistically determine the exact extent to which the degradation profile is switch-like. Our results suggest design principles for protein degradation switches which might be a widespread mechanism for precise regulation of cellular processes such as cell cycle progression

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk