bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caveolin-3 KO disrupts t-tubule structure and decreases t-tubularICadensity in mouse ventricular myocytes
Authors: Bryant Simon M. , Kong Cherrie H. T. , Watson Judy J. , Gadeberg Hanne C. , Roth David M. , Patel Hemal H. , Cannell Mark B. , James Andrew F. , Orchard Clive H. 
Published: July 2018

Caveolin-3 (Cav-3) is a protein that has been implicated in t-tubule formation and function in cardiac ventricular myocytes. In cardiac hypertrophy and failure, Cav-3 expression decreases, t-tubule structure is disrupted, and excitation-contraction coupling is impaired. However, the extent to which the decrease in Cav-3 expression underlies these changes is unclear. We therefore investigated the structure and function of myocytes isolated from the hearts of Cav-3 knockout (KO) mice. These mice showed cardiac dilatation and decreased ejection fraction in vivo compared with wild-type control mice. Isolated KO myocytes showed cellular hypertrophy, altered t-tubule structure, and decreased L-type Ca2+channel current ( ICa) density. This decrease in density occurred predominantly in the t-tubules, with no change in total ICa, and was therefore a consequence of the increase in membrane area. Cav-3 KO had no effect on L-type Ca2+channel expression, and C3SD peptide, which mimics the scaffolding domain of Cav-3, had no effect on ICain KO myocytes. However, inhibition of PKA using H-89 decreased ICaat the surface and t-tubule membranes in both KO and wild-type myocytes. Cav-3 KO had no significant effect on Na+/Ca2+exchanger current or Ca2+release. These data suggest that Cav-3 KO causes cellular hypertrophy, thereby decreasing t-tubular ICadensity.NEW & NOTEWORTHY Caveolin-3 (Cav-3) is a protein that inhibits hypertrophic pathways, has been implicated in the formation and function of cardiac t-tubules, and shows decreased expression in heart failure. This study demonstrates that Cav-3 knockout mice show cardiac dysfunction in vivo, while isolated ventricular myocytes show cellular hypertrophy, changes in t-tubule structure, and decreased t-tubular L-type Ca2+current density, suggesting that decreased Cav-3 expression contributes to these changes in cardiac hypertrophy and failure.
Therapeutic Potential of Leelamine, a Novel Inhibitor of Androgen Receptor and Castration-Resistant Prostate Cancer
Authors: Singh Krishna B. , Ji Xinhua , Singh Shivendra V. 
Published: July 2018

Abstract
Clinical management of castration-resistant prostate cancer (CRPC) resulting from androgen deprivation therapy remains challenging. CRPC is driven by aberrant activation of androgen receptor (AR) through mechanisms ranging from its amplification, mutation, post-translational modification, and expression of splice variants (e.g., AR-V7). Herein, we present experimental evidence for therapeutic vulnerability of CRPC to a novel phytochemical, leelamine (LLM), derived from pine tree bark. Exposure of human prostate cancer cell lines LNCaP (an androgen-responsive cell line with mutant AR), C4-2B (an androgen-insensitive variant of LNCaP), and 22Rv1 (a CRPC cell line with expression of AR-Vs), and a murine prostate cancer cell line Myc-CaP to plasma achievable concentrations of LLM resulted in ligand-dependent (LNCaP) and ligand-independent (22Rv1) growth inhibition in vitro that was accompanied by downregulation of mRNA and/or protein levels of full-length AR as well as its splice variants, including AR-V7. LLM treatment resulted in apoptosis induction in the absence and presence of R1881. In silico modeling followed by luciferase reporter assay revealed a critical role for noncovalent interaction of LLM with Y739 in AR activity inhibition. Substitution of the amine group with an isothiocyanate functional moiety abolished AR and cell viability inhibition by LLM. Administration of LLM resulted in 22Rv1 xenograft growth suppression that was statistically insignificant but was associated with a significant decrease in Ki-67 expression, mitotic activity, expression of full-length AR and AR-V7 proteins, and secretion of PSA. This study identifies a novel chemical scaffold for the treatment of CRPC. Mol Cancer Ther; 17(10); 2079–90. ©2018 AACR.
Оцінка ефективності лікування хронічного катарального гінгівіту в працівників птахофабрик за даними клінічних спостережень та параклінічних індексів
Authors: Pupin T. I. , Kardashevska O. I. 
Published: July 2018

Summary. The research of periodontal diseases provides the basis for a generalized conclusion that the occurrence of pathological changes in the teeth-containing tissues occurs when the general state of the organism changes, due to the action of a number of endogenous and exogenous factors that determine the approaches to the treatment and prevention of these diseases. Despite the automation and mechanization of poultry farms, an increasing percentage of poultry workers are exposed to adverse productive factors, which lead to occupational diseases, in particular periodontal diseases.The aim of the study – to evaluate the effectiveness of the developed scheme of treatment of chronic catarrhal gingivitis in poultry factory workers according to clinical observations and paraclinical indices.Materials and Methods. To evaluate the effectiveness of the treatment of chronic catarrhal gingivitis (CCG), there were 39 employees of poultry farms, whо were divided into 2 equal groups: the main (20 persons), in which treatment was performed according to the scheme we developed and control (19 people), where patients were treated for according to the “Protocols of the Ministry of Health of Ukraine” the provision of medical care in the specialty “Therapeutic Dentistry”.Results and Discussion. In case of poultry factory workers, patients with CCG, 1 month after treatment, the index of PI in the main group was (0.45±0.03) points, the value of the index of PMA decreased by 2 times: (12.28±2.28) %, the value of the index OHI- S corresponded to satisfactory hygiene: (0.98±0.02) points. Six months after treatment, patients in the main group who tested for stabilization of the periodontal index of PI with a value of (0.45±0.04) points, a decrease in the PMA index to (11.79±2.23) and an OHI-S index of (1.08±0.01) score. In 12–18 months, the value of the index of PI in the main group was (0.63±0.23) points, the index PMA fell to (14.37±2.26) %. The condition of oral hygiene according to the OНI-S index in the main group was assessed as “satisfactory” with a value of (1.28±0.04) points.Conclusions. In the main group, the elimination of the inflammatory process in the gums was clinically observed at all stages, which was confirmed by a decrease in the periodontal indices PMA up to (11.79±2.23) %, PI up to (14.37±2.26) %, a decrease in the index of the hygiene index OHI-S to (1.08±0.01) points. Thus, the proposed therapeutic model allowed to increase the efficiency and reduce the duration of treatment of chronic catarrhal gingivitis in workers of poultry farms.
Risk adapted approaches to prophylaxis of thrombotic complications at gisterectomy
Authors: Kryvokulsky B. D. , Zhulkevich I. V. 
Published: July 2018

Мета роботи: провести оцінку стану системи гемостазу, розробити індивідуальні підходи для визначення груп ризику та профілактику тромботичних ускладнень (ТУ) у хворих на рак ендометрія (РЕ) на доопераційному етапі. Оптимізувати хірургічну тактику при виявленні тромбів у судинах малого таза при гістеректомії.Матеріали і методи. При дослідженні використано загальноклінічні методи обстеження: лабораторні, ультразвукове дослідження, гістологічні методи; математичний, статистичний – для аналізу та узагальнення данних у пакеті Statgraph (v.3.0).Результати досліджень та їх обговорення. До операції рівень D-димеру у 58,50 % хворих перевищував норму, що свідчило про активацію системи зсідання крові та загрозу розвитку ТУ, що було підтверджено у 5,4 % хворих, завдяки проведеню еластографії судин малого таза. До операції спостерігали збільшення рівня D-димеру у 86 (58,50 %) хворих, при операційному втручанні у 109 хворих (74,15 %).Під час гістеректомії проведено ревізію кукс судин малого таза на наявність тромбів. У 11,56 % хворих при ревізії кукс судин малого таза виявлені тромботичні маси за лінійним розміром були від 0,3 до 5,4 см, що підтверджено гістологічним дослідженням. У 17 пaцієнток під час проведення тромбектомії було виділено 19 тромбів.Створено математичну модель для рівняння множинної регресії, яка може бути використана для прогнозу наявності (відсутності) тромбів у венах малого таза.Розроблено алгоритм оптимізації діагностичної та хірургічної тактики у хворих РЕ з врахуванням ризику можливих ТУ, який дозволяє оптимізувати діагностичну і хірургічну тактику, що сприяє активному виявленню тромбів у хворих із РЕ.
QTc Interval and Risk of Cardiac Events in Adults With Anorexia Nervosa
Authors: Frederiksen Tanja Charlotte , Krogh Christiansen Morten , Charmoth Østergaard Pernille , Hove Thomsen Per , Graff Claus , Clausen Loa , Kjærulf Jensen Henrik 
Published: July 2018

Background:
The literature contains several cases of anorexia nervosa (AN) patients with prolonged QTc interval. However, the risk of prolonged QTc interval is controversial and the risk of cardiac events in AN patients has yet to be investigated.

Methods:
We estimated the difference in mean QTc interval and relative risk of borderline prolonged QTc (>440 ms) and prolonged QTc (>460 ms) between 430 adult women AN patients and 123 healthy controls using 3 correction formulas. In a follow-up study, we estimated the risk of a primary end point (a composite of ventricular tachycardia, aborted cardiac arrest, and cardiac arrest) in AN patients compared with a population-based cohort derived from the Danish Civil Register.

Results:

Mean QTc for AN patients was 408 ms (Hodges), 402 ms (Fridericia), and 399 ms (Bazett). Hodges’ found a slightly increased mean QTc (6.8 ms, 95% confidence interval, 1.6–12.0;
P
=0.01) and percentage with QTc >440 ms in AN patients (relative risk, 3.7, 95% confidence interval, 1.4–10.3;
P
=0.01), not observed with Fridericia’s and Bazett’s formulas. There was no difference in the risk of QTc >460 ms between AN patients and healthy controls. During a median follow-up of 10.1 years, AN patients had an increased risk of the primary end point compared with the population-based cohort (hazard ratio, 10.4, 95% confidence interval, 2.6–41.6;
P
=0.001). However, absolute numbers were small with cumulative incidences of 0.5% and 0.07%, respectively, after 10 years. No events occurred in any AN patient with QTc >440 ms. All-cause mortality was also significantly increased in AN patients compared with the population-based cohort (hazard ratio, 11.2, 95% confidence interval, 5.1–24.5;
P
<0.001).

Conclusions:
Overall, there was no difference in mean QTc interval or risk of prolonged QTc between AN patients and healthy controls. However, AN patients had a notably increased all-cause mortality, as well as an increased risk of cardiac events, which was not related to the baseline QTc interval.
Multisite Generalization of the SHArP Weather Generator
Authors: Smith Kimberly , Strong Courtenay , Rassoul-Agha Firas 
Published: July 2018

AbstractGeneralization of point-scale stochastic weather generators to simultaneously produce output at multiple sites provides more powerful support for hydrology and climate change impact studies. Generalization preserves the statistical properties of each individual site while maintaining proper spatial correlation over the domain. Here, generalization of the daily precipitation and temperature components of the stochastic harmonic autoregressive parametric (SHArP) weather generator is presented. The generalization process for temperature involves conversion of vector time series to matrix time series that capture between-site covariances of maximum and minimum daily temperature. Between-site temperature covariances depend on spatial precipitation-occurrence patterns (POPs), of which there are up to 2M for M sites. To dramatically reduce the number of covariance matrices that drive temperature, multisite SHArP uses empirical orthogonal function analysis to categorize the POPs and harmonic smoothing to reduce the number of parameters describing the temporal evolution (annual cycle) of the elements in the covariance matrices. By modeling precipitation-regime-specific residuals, the model is shown to capture statistically significant spatial and temporal contrasts in observed temperature covariance. For precipitation simulation, we extend existing techniques by adding a trend term to the occurrence and amount parameters. Multisite generalization of the framework is illustrated by simulating stochastic historical and future temperature and precipitation across complex terrain over northern Utah on the basis of historical station observations and historical and future statistically downscaled climate model output.
Use of mirtazapine in patients with chronic breathlessness: A case series
Authors: Lovell Natasha , Bajwah Sabrina , Maddocks Matthew , Wilcock Andrew , Higginson Irene J 
Published: July 2018

Background: Breathlessness remains a common and distressing symptom in people with advanced disease with few effective treatment options. Repurposing of existing medicines has been effective in other areas of palliative care, for example, antidepressants to treat pain, and offers an opportunity to deliver improved symptom control in a timely manner. Previous case series have shown reduced breathlessness following the use of sertraline (a selective serotonin reuptake inhibitor) in people with chronic obstructive pulmonary disease. Cases: Six cases where mirtazapine, a noradrenergic and specific serotonergic antidepressant, was used to treat chronic breathlessness in advanced lung disease. Case management: All cases received mirtazapine at a starting dose of 15 mg, prescribed under the care of their primary care physician. Cases had been receiving mirtazapine for a variable time period (2 weeks to 5 months) at the time of the interviews. Case outcome: All cases reported less breathlessness and being able to do more. They described feeling more in control of their breathing, and being able to recover more quickly from episodes of breathlessness. Some cases also reported beneficial effects on anxiety, panic, appetite and sleep. No adverse effects were reported. Discussion: Patients with chronic breathlessness in this case series reported benefits during mirtazapine treatment. To determine the effectiveness of mirtazapine in alleviating breathlessness and improving quality of life in chronic lung disease, blinded randomised trials are warranted.
Surgical treatment for terrible triad injury of the elbow with anteromedial coronoid fracture through a combined surgical approach
Authors: Liu Guanyi , Hu Jingen , Ma Weihu , Li Ming , Xu Rongming , Pan Zhijun 
Published: July 2018

Summary Objective To report the results of the surgical treatment of terrible triad injury with anteromedial coronoid fracture through a combined surgical approach. Methods This retrospective study evaluated data from patients who underwent surgery to repair terrible triad injuries and anteromedial coronoid fractures. Surgical treatment involved radial head repair or replacement, medial and lateral collateral ligament repair, and coronoid fracture fixation through combined approaches. Evaluations were performed using the Mayo Elbow Performance Score (MEPS) and anteroposterior and lateral radiographs of the elbow. Results Twenty-two patients (15 males, seven females; mean ± SD age, 47.5 ± 11.4 years) were enrolled in this study. Fracture union and concentric reduction of both the ulnotrochlear and radiocapitellar articulations were achieved in all patients. The mean ± SD follow-up was 31.6 ± 11.9 months. The mean ± SD arc of flexion–extension was 110.3° ± 26.3° and arc of forearm rotation was 139.5° ± 17.1°. The mean ± SD MEPS was 88.1 ± 12.2 points, with results classified as excellent in eight elbows, good in ten, and fair in four. Six patients had radiographic signs of post-traumatic arthritis. Three patients required secondary surgeries. Conclusion Combined surgical approaches can be considered for the treatment of terrible triad injuries in association with anteromedial coronoid fractures.
Minimum Wages, Employment, and College Enrollment
Authors: Wescher Lance , Hutchinson Travis , Rannou Anna 
Published: July 2018

Most studies of the effects of minimum wage laws look exclusively at the labor market. This article investigates the less-researched topic of the effects of a minimum wage increase on enrollment in undergraduate higher education institutions in the United States. With a higher opportunity cost of pursuing an education given a higher minimum wage, potential students may opt to work instead of attend college. Conversely, if an increase in the minimum wage raises the unemployment rate for young workers, more people may enroll in college, as they are unable to find employment. Using restricted geocode variables and panel data from National Longitudinal Survey of Youth (NLSY97) over a period of time in which every state saw an increase in its effective minimum wage, we find that higher minimum wages do correspond to lower levels of college enrollment. We use a multinomial probit model to examine how tradeoffs are made between employment and college enrollment. Finally, we examine the transition path between college enrollment and employment. JEL Classification: I23, J24, and E24.
Prophylactic metoclopramide use in trauma patients given tramadol: A randomised, double-blinded, placebo-controlled trial
Authors: Choo Kim Hoon , Manikam Rishya A/L , Yoong Khadijah Poh Yuen , Kandasamy Vanitha A/P 
Published: July 2018

Background: Tramadol is a common analgesia used in Emergency Department for trauma patients. However, it causes multiple side effects, most notably nausea and vomiting. Objectives: The aim of this study is to determine whether routine administration of prophylactic metoclopramide in patients receiving intravenous tramadol for injuries of extremities is beneficial. Method: A randomised, double-blinded, placebo-controlled trial was carried out on 200 trauma patients requiring tramadol for acute pain in Emergency & Trauma Department of Sarawak General Hospital. Patients were randomised into two groups, group one received metoclopramide 10 mg intravenously while group two received placebo. Nausea severity (measured on a visual analogue scale) before and after tramadol administration, number of episodes of vomiting and patients’ demographic data were recorded. Results: A total of 191 patients were recruited, in which the metoclopramide group had 96 patients while the placebo group had 95 patients. In total, 5 out of 191 patients had significant worsening of nausea severity and all were from the placebo group (5.26%). The difference was statistically significant (p = 0.029, Fisher’s exact test). Only 1 out of 191 patients vomited and was from the placebo group. No adverse reaction was reported in both groups of patients. Conclusion: Routine administration of intravenous metoclopramide may be beneficial in musculoskeletal trauma patients receiving tramadol.
Early detection of dementia: The knowledge and attitudes of primary care physicians in Hong Kong
Authors: Leung Cheuk Wing , Lam Tai Pong , Wong Kwai Wing , Chao Vai Kiong David 
Published: July 2018

BackgroundDementia affects people worldwide and its prevalence is growing. Early detection of dementia by primary care physicians can be beneficial; thus, their knowledge and attitudes about this issue are important.ObjectiveTo assess primary care physicians’ knowledge and attitudes about the early detection of dementia in Hong Kong.MethodsThis was a mixed methods (qualitative and quantitative) study. Four focus groups with a purposive sample of 31 primary care physicians were interviewed, and a questionnaire-survey was completed and returned by 437 primary care physicians.ResultsParticipants all agreed that the early detection of dementia would benefit patients and primary care physicians should be capable of making such diagnoses. Confidence in making an early diagnosis varied; physicians tended to overlook symptoms in the early stages. All agreed that more training is needed at the post-graduate level of medical education.ConclusionsParticipants had positive attitudes towards early detection of dementia; however, their confidence and ability to make an early diagnosis varied.
What can we learn from second generation digital natives? A qualitative study of undergraduates’ views of digital health at one London university
Authors: Cowey Aasha E , Potts Henry W W 
Published: July 2018

Objectives We live in a digital age and opportunities within healthcare are increasing, ranging from patient portals to wearable devices. Today’s undergraduates are second generation digital natives and are at a critical point of becoming more autonomous in their healthcare interactions. This study aims to understand their experiences of both digital and broader healthcare. This will enable a better understanding of implications for national policy, individual healthcare organisations and further research. Methods Undergraduates aged 18–21 participated in individual interviews or focus groups. Inductive thematic analysis was undertaken. Negative member checking and feedback on emerging themes from both participants and experts were used to increase the validity of the study. Results Twenty-four undergraduates participated in the study, including a high proportion of international students. Thematic analysis revealed 16 themes. Six key themes explored in this paper are: generation gap; impact on healthcare professionals (HCPs); use of technology to replace or enhance HCP interactions; use of technology to support administration/transactional activities; paper vs electronic; and personally held health and fitness data. Conclusion This paper highlights recommendations for the undergraduate cohort and wider populations including better articulation of benefits, making digital options more personalised and interactive, and raising awareness of dangerous ‘obsessive’ behaviour around health and fitness apps. Some of our findings challenge the assumption that this generation will automatically accept digital initiatives, including the importance this cohort continues to place on face-to-face interactions. In response, we offer some suggestions to improve awareness, utilisation and acceptance of digital health.