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48) or all-cause mortality (beta-blocker user 1.13 [0.78-1.64]; non-user 0.89 [0.62-1.26]; interaction P = 0.35), in patients using beta-blockers. Aclidinium reduced annualized rate of moderate-to-severe COPD exacerbation (beta-blocker user rate ratio 0.75 [95% CI 0.60-0.94, P = 0.013]; non-user 0.79 [0.67-0.93, P = 0.005]), delayed time to first exacerbation, and improved lung function versus placebo. There was greater trough FEV
benefit in beta-blocker users versus non-users (least squares mean difference at 52weeks 111mL [95% CI 74mL-147mL] versus 69mL [42mL-97mL]; interaction P = 0.041).
This post hoc analysis supports long-acting anti-muscarinic use with concomitant beta-blockers in patients with moderate-to-very severe COPD and cardiovascular comorbidity.
ClinicalTrials.gov, NCT01966107, Registered 16 October 2013, https//clinicaltrials.gov/ct2/show/NCT01966107 .
ClinicalTrials.gov, NCT01966107, Registered 16 October 2013, https//clinicaltrials.gov/ct2/show/NCT01966107 .
Our study aimed to explore the clinical therapeutic effects of ultrasound-guided five-point injection of botulinum toxin type A for patients with trapezius hypertrophy.
Twenty female patients diagnosed with trapezius hypertrophy were enrolled in this study. The thicknesses of the trapezius muscle were measured by using the ultrasound scanner to locate the thickest point of trapezius, followed by labelling the other four points around the first point. Botulinum toxin type A was injected bilaterally (50IU/side, 5 points/side) in the trapezius muscle of these patients. The surgery effects were evaluated by thicknesses of the trapezius muscle, intramuscular needle electromyographic and electroneurographic examinations, appearance changes and patients’ satisfactions.
Statistically significant differences in thicknesses of the trapezius muscle were observed at 4weeks (p < 0.001), 12weeks (p < 0.001), 20weeks (p < 0.001), 28weeks (p = 0.011), 36weeks (p = 0.022), and 44weeks (p = 0.032) after surgery. The latencies of trapezius muscle became longer at 12weeks after surgery (left 2.40ms, right 2.53ms vs. left 1.75ms, right 2.00ms). Electroneurographic results showed amplitude reduction of compound muscle action potentials (CMAPs) at 12weeks after surgery (left 1.91 uV, right 3.10 uV vs. left 15.00 uV, right 15.40 uV). Obvious appearance changes were revealed at 12weeks after surgery. All of 80% patients were very satisfied, 15% patients were relatively satisfied, and 5% patients were not satisfied with the surgery.
Ultrasound-guided five-point injection of botulinum toxin type A might be effective for patients with trapezius hypertrophy.
Ultrasound-guided five-point injection of botulinum toxin type A might be effective for patients with trapezius hypertrophy.
Managerial commitment is important for effective design and implementation of citizen charter to assure the quality of health service delivery as per the standards depicted in the document. Hence the objective of this study is to assess the level of managerial commitment towards implementation of the citizen charter standards and associated factor in Jimma zone public hospitals.
A Facility based cross-sectional study design was employed in Jimma zone public hospitals from March 14 to May 16, 2019 and 422 health managers who were currently working at all levels of management were participated in the study. After checking its completeness, the data was entered into EPI data version 3.1 and exported to SPSS version 20 for statistical analysis. Factor analysis was conducted. Simple and multiple linear regression were done using 95%CI and significance was declared at P < 0.05. All assumptions of linear regression and principal component analysis were checked.
The percentages mean score of managerial commiedium. Hence, all levels of managers to consider and maintain factors identified in this study in their management practice to foster a higher level of managerial commitment towards implementation of citizen charter standards in jimma zone public hospitals.
Poly (ADP)-ribose polymerase (PARP) inhibitors have entered routine clinical practice for the treatment of high-grade serous ovarian cancer (HGSOC), yet the molecular mechanisms underlying treatment response to PARP1 inhibition (PARP1i) are not fully understood.
Here, we used unbiased mass spectrometry based proteomics with data-driven protein network analysis to systematically characterize how HGSOC cells respond to PARP1i treatment.
We found that PARP1i leads to pronounced proteomic changes in a diverse set of cellular processes in HGSOC cancer cells, consistent with transcript changes in an independent perturbation dataset. We interpret decreases in the levels of the pro-proliferative transcription factors SP1 and β-catenin and in growth factor signaling as reflecting the anti-proliferative effect of PARP1i; and the strong activation of pro-survival processes NF-κB signaling and lipid metabolism as PARPi-induced adaptive resistance mechanisms. Based on these observations, we nominate several protein targets for therapeutic inhibition in combination with PARP1i. When tested experimentally, the combination of PARPi with an inhibitor of fatty acid synthase (TVB-2640) has a 3-fold synergistic effect and is therefore of particular pre-clinical interest.
Our study improves the current understanding of PARP1 function, highlights the potential that the anti-tumor efficacy of PARP1i may not only rely on DNA damage repair mechanisms and informs on the rational design of PARP1i combination therapies in ovarian cancer.
Our study improves the current understanding of PARP1 function, highlights the potential that the anti-tumor efficacy of PARP1i may not only rely on DNA damage repair mechanisms and informs on the rational design of PARP1i combination therapies in ovarian cancer.
Antisocial behaviour is a common phenomenon in childhood and adolescence. Information on psychosocial risk and resource factors for antisocial behaviour are important for planning targeted prevention and early intervention programs. The current study explores risk and resource factors of antisocial behaviour in children and adolescents based on population-based longitudinal data.
We analysed longitudinal data from the German BELLA study (n = 1145; 11 to 17 year-olds) measured at three measurement points covering two years. Latent growth analysis, linear regression models and structural equation modelling were used to explore cross-sectional and longitudinal data.
Based on baseline data, we found that stronger self-efficacy and worse family climate were each related to stronger antisocial behaviour. Longitudinal data revealed that more severe parental mental health problems, worse family climate at baseline, deteriorating family climate over time, and more social support were each associated with increasing antisocial behaviour over time. We further found a moderating effect for family climate.
Our study provides important exploratory results on psychosocial risk, resource and protective factors in the context of antisocial behaviour in children and adolescents, which need confirmation by future research. Our exploratory results point in the direction that family-based interventions for antisocial behavior in children and adolescents may benefit from considering the family climate.
Our study provides important exploratory results on psychosocial risk, resource and protective factors in the context of antisocial behaviour in children and adolescents, which need confirmation by future research. Our exploratory results point in the direction that family-based interventions for antisocial behavior in children and adolescents may benefit from considering the family climate.Coronary heart disease (CHD) is a common ischaemic heart disease whose pathological mechanism has not been fully elucidated. Single target drugs, such as antiplatelet aggregation, coronary artery dilation and lipid-lowering medicines, can relieve some symptoms clinically but cannot effectively prevent and treat CHD. Accumulating evidence has revealed that alterations in GM composition, diversity, and richness are associated with the risk of CHD. The metabolites of the gut microbiota (GM), including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs) and bile acids (BAs), affect human physiology by activating numerous signalling pathways. Due to the advantage of multiple components and multiple targets, traditional Chinese medicine (TCM) can intervene in CHD by regulating the composition of the GM, reducing TMAO, increasing SCFAs and other CHD interventions. check details We have searched PubMed, Web of science, Google Scholar Science Direct, and China National Knowledge Infrastructure (CNKI), with the use of the keywords “gut microbiota, gut flora, traditional Chinese medicine, herbal medicine, coronary heart disease”. This review investigated the relationship between GM and CHD, as well as the intervention of TCM in CHD and GM, and aims to provide valuable insights for the treatments of CHD by TCM.
Endometriosis, the presence of active endometrial tissue outside the lining membrane of the uterine cavity, is a common disease in women of childbearing age. The ectopic endometrium has some characteristics of tumor tissue, including invasive and migratory abilities. In addition, endometriosis is associated with inflammation and reduced cellular apoptosis.
Western blot analysis, qPCR, immunohistochemistry, immunofluorescence microscopy, Transwell assay, wound healing assay, and TUNEL staining.
Interleukin-1β (IL-1β) induced WEE1 expression in endometrial stromal cells (ESCs), suggesting that WEE1 may be upregulated during the endometriosis-induced inflammatory response. Overexpression of WEE1 in cultured ESCs promoted ESC migration while inhibiting apoptosis, whereas WEE1 knockdown reduced ESC migration while promoting apoptosis. Inhibition of WEE1 attenuates fibrosis in ESCs and female C57BL/6 J mice. This pro-fibrotic effect of WEE1 was significantly decreased by treatment with the Wnt/β-catenin inhibitor XAV939, suggesting that WEE1 acts via the Wnt/β-catenin signaling pathway.
Our study demonstrates that WEE1 promotes ESC migration and fibrosis via the Wnt/β-catenin signaling pathway. Thus, WEE1 may serve as a potential therapeutic target for the treatment of endometriosis.
Our study demonstrates that WEE1 promotes ESC migration and fibrosis via the Wnt/β-catenin signaling pathway. Thus, WEE1 may serve as a potential therapeutic target for the treatment of endometriosis.
To examine racial/ethnic and educational inequities in the relationship between state-level restrictive abortion policies and adverse birth outcomes from 2005 to 2015 in the United States.
Using a state-level abortion restrictiveness index comprised of 18 restrictive abortion policies, we conducted a retrospective longitudinal analysis examining whether race/ethnicity and education level moderated the relationship between the restrictiveness index and individual-level probabilities of preterm birth (PTB) and low birthweight (LBW). Data were obtained from the 2005-2015 National Center for Health Statistics Period Linked Live Birth-Infant Death Files and analyzed with linear probability models adjusted for individual- and state-level characteristics and state and year fixed-effects.
Among 2,250,000 live births, 269,253 (12.0%) were PTBs and 182,960 (8.1%) were LBW. On average, states had approximately seven restrictive abortion policies enacted from 2005 to 2015. Black individuals experienced increased probability of PTB with additional exposure to restrictive abortion policies compared to non-Black individuals.