bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammalian Target of Rapamycin Complex 1 Activation Disrupts the Low-Density Lipoprotein Receptor Pathway: A Novel Mechanism for Extracellular Matrix Accumulation in Human Peritoneal Mesothelial Cells
Authors: Liu Jing , Zhu Wei , Jiang Chun-Ming , Feng Yuan , Xia Yang-Yang , Zhang Qing-Yan , Xu Peng-Fei , Zhang Miao 
Published: November 2018

Peritoneal fibrosis (PF) is characterized by progressive extracellular matrix (ECM) accumulation. Increasing evidence has suggested that ECM synthesis was increased in human peritoneal mesothelial cells (HPMCs) under high-glucose conditions, but the effects of high-glucose peritoneal dialysis solution (PDS) on ECM synthesis have not been fully elucidated. The aim of this study was to explore the potential mechanisms of high-glucose PDS-induced production of ECM in HPMCs. HPMCs were stimulated by high-glucose PDS. The activity of mammalian target of rapamycin complex 1 (mTORC1) was inhibited by rapamycin or regulatory-associated protein of mTOR (raptor) siRNA. Morphological changes in the cells were observed under an inverted microscope. Oil red O, filipin staining and high-performance liquid chromatography were used to examine lipid accumulation. The expression of low-density lipoprotein receptor (LDLr) regulation, the mTORC1 pathway and ECM-associated markers were assessed by real-time polymerase chain reaction and western blot analysis. The results showed that after treatment with PDS, HPMCs showed notable elongation consistent with the morphology of myofibroblasts, and the expression of ECM proteins such as α-smooth muscle actin, fibroblast specific protein-1 and collagen I was increased. In addition, there was a parallel increase in the ECM and lipid accumulation. Moreover, the effect of intracellular lipid deposition was closely correlated with the dysregulation of LDLr, which was mediated through the upregulation of LDLr, sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), and SREBP-2 and through the enhanced coexpression of the SCAP with the Golgin. Further analysis showed that PDS enhanced the protein phosphorylation of mTOR, eukaryotic initiation factor 4E-binding protein 1, and p70 S6 kinase. Interestingly, blocking mTORC1 activity reversed the dysregulation of LDLr, even in the presence of PDS. These effects were also accompanied by a decrease in the expression of ECM components. Our findings demonstrated that increased mTORC1 activity exacerbated ECM formation in HPMCs by disrupting LDLr regulation, which contributed to lipid disorder-mediated PF.
ПЕРВИННІ ІМУНОДЕФІЦИТИ: РЕГІОНАЛЬНІ, НАЦІОНАЛЬНІ ТА ГЛОБАЛЬНІ ВИКЛИКИ
Authors: Boyarchuk O. R. , Volokha A. P. , Hariyan T. V. , Dmytrash L. M. 
Published: November 2018

Первинні імунодефіцити – група захворювань, що зумовлені генетичними дефектами та проявляються порушенням функції імунної системи. За останні роки спостерігається позитивна динаміка виявлення первинних імунодефіцитів в Україні та в Тернопільській області, проте рання діагностика захворювань залишається важливою проблемою.
Мета дослідження – проаналізувати проблеми діагностики та лікування первинних імунодефіцитів в Україні та регіоні для визначення напрямків їх удосконалення. Протягом останніх років у країнах Східної Європи та в Україні відбулися значні зрушення в діагностиці первинних імунодефіцитів. Кількість захворювань в Україні за останні 10 років зросла втричі, проте ще значна кількість випадків залишається не виявленою. З 2012 р. в Україні ведеться реєстр хворих з первинними імунодефіцитами. В Тернопільській області спостерігається недостатнє виявлення дефектів антитілоутворень та комбінованих імунодефіцитів, порівняно з Україною та Європою, не використовуються усі можливості діагностики імунодефіцитів із синдромними ознаками, зокрема Ніймеген-синдрому та синдрому Ді-Джорджі. Проведений аналіз показав недостатню обізнаність студентів-медиків, лікарів-інтернів різних спеціальностей та практичних лікарів як первинної ланки, так і вузьких спеціалістів щодо діагностики та ведення первинних імунодефіцитів. Міждисциплінарна співпраця фахівців різних галузей (первинної ланки, імунологів, алергологів, пульмонологів, ревматологів, хірургів, неонатологів, оториноларингологів, гастроентерологів тощо) є важливим аспектом у питаннях діагностики і лікування пацієнтів із первинними імунодефіцитами. Розширення спектра генетичної діагностики первинних імунодефіцитів, забезпечення пацієнтів усіх вікових груп високоякісними імуноглобулінами для внутрішньовенного та підшкірного введень, доступність алогенної трансплантації гемопоетичних стовбурових клітин від родинного та сумісного неродинного донора є на сьогодні основними викликами розвитку дитячої імунології в Україні та в регіоні. Впровадження моделі освіти лікарів та підвищення громадської настороженості з удосконаленням інфраструктури діагностики первинних імунодефіцитів дозволить покращити ранню діагностику захворювань та якість життя дітей.
ВИБІР МЕТОДУ РЕКОНСТРУКЦІЇ ДЕФЕКТІВ ПОКРИВНИХ ТКАНИН ТУЛУБА ТА КІНЦІВОК У ТРАВМОВАНИХ ХВОРИХ
Authors: Ponomarenko E. V. 
Published: November 2018

Об’єм реконструктивних втручань із відновлення дефектів покривних тканин, які виникають унаслідок травматичного ушкодження, визначає результат як з функціональної, так і з естетичної точки зору.
Мета дослідження – обрати оптимальний метод відновно-реконструктивного втручання із закриття ранових дефектів тулуба та кінцівок після травми.
Матеріали і методи. У роботі проаналізовано дані 242 хворих із дефектами покривних тканин тулуба та кінцівок, які виникли унаслідок механічного ушкодження за період 2008–2016 рр. Пацієнтам виконали 697 оперативних втручань, з них 492 (70,6 %) операцій з приводу відновлення ушкоджених тканин.
Результати досліджень та їх обговорення. Хворих поділили на 4 групи залежно від розмірів, глибини та ступеня ушкодження м’яких тканин та інших структур тулуба й кінцівок. Перша група – 44 (18,2 %) хворих з обмеженою (до 5 см у діаметрі) ділянкою ушкодження шкіри та підлеглих тканин до глибокої фасції. Їм було виконано 61 (8,8 %) втручання. Друга група – 67 (27,7 %) хворих із великою та надвеликою рановою поверхнею й ушкодженням м’яких тканин нижче глибокої фасції. У цій групі виконано 144 (20,6 %) оперативних втручань. Третю групу склали 90 (37,2 %) пацієнтів з дефектами покривних тканин, які виникли разом або унаслідок ушкодження кістково-суглобового апарату. Було виконано 272 (39 %) операцій. Четверта група – 41 (16,9 %) хворих з поєднаною або множинною травмою, що супроводжується ушкодженням магістральних судин, нервів частковим або повним відокремленням кінцівки. В цій групі було виконано 220 (31,6 %) операцій.
Висновки. Використання васкуляризованих клаптів у 21,3 % усіх можливих реконструкцій підвищило функціональні та косметичні результати лікування, знизило кількість ішемічних розладів та запальних процесів (1,9 % післяопераційних ускладнень). Ретельний підхід до вибору відновного втручання дефектів покривних тканин, які зумовлені механічними ушкодженнями, дозволив досягти задовільних результатів у 98,9 % випадків.
Lung cancer risk stratification using methylation profile in the oral epithelium
Authors: Harada Hiroaki , Miyamaoto Kazuaki , Kimura Masami , Ishigami Tetsuro , Taniyama Kiyomi , Okada Morihito 
Published: November 2018

Background Assuming that the entire airway is affected by the same inhaled carcinogen, similar molecular alterations may occur in the lung and oral cavity. Thus, we hypothesized that DNA methylation profiles in the oral epithelium may be a promising biomarker for lung cancer risk stratification. Methods A methylation-specific polymerase chain reaction was performed on oral epithelium from 16 patients with lung cancer and 32 controls without lung cancer. Genes showing aberrant methylation profiles in the oral epithelium were compared between patients and controls. Results The analysis revealed that HOXD11 and PCDHGB6 were methylated more frequently in patients than in controls ( p = 0.0055 and p = 0.0247, respectively). Combined analyses indicated that 8 of 16 (50%) patients and 3 of 32 (9.4%) controls showed DNA methylation in both genes ( p = 0.0016). Among the population limited to current and former smokers, 6 of 11 (54.5%) patients showed methylation in both genes, compared to 1 of 17 (5.9%) controls ( p = 0.0037). In a subgroup analysis limited to the population above 50-years old, 8 of 16 (50%) patients and 2 of 16 (12.5%) controls showed methylation in both genes ( p = 0.0221). Conclusions The results of this study indicate that specific gene methylation in the oral epithelium might be a promising biomarker for lung cancer risk assessment, especially among smokers. Risk stratification through the analysis of DNA methylation profiles in the oral epithelium may be a useful and less invasive first-step approach in an efficient two-step lung cancer screening strategy.
Validity assessment of a simulation module for robot-assisted thoracic lobectomy
Authors: Whittaker George , Aydin Abdullatif , Raveendran Sinthuri , Dar Faizan , Dasgupta Prokar , Ahmed Kamran 
Published: November 2018

Background Training for robot-assisted thoracic lobectomy remains an issue, prompting the development of virtual reality simulators. Our aim was to assess the construct and face validity of a new thoracic lobectomy module on the RobotiX Mentor, a robotic surgery simulator. We also aimed to determine the acceptability and feasibility of implementation into training. Methods This prospective, observational, and comparative study recruited novice (n = 16), intermediate (n = 9), and expert (n = 5) participants from King's College London, the 25th European Conference on General Thoracic Surgery, and the Society of Robotic Surgery conference 2018. Each participant completed two familiarization tasks followed by the Guided Robotic Lobectomy module and an evaluation questionnaire. Outcome measures were compared using Mann-Whitney U tests. Results Construct validity was demonstrated in 12/21 performance evaluation metrics. Significant differences between groups were found in all metrics including: time taken to complete module, vascular injury, respect for tissue, number of stapler firings, time instruments out of view, number of instrument collisions, and number of movements. Participants deemed aspects of the simulator (mean 3/5) and module (3/5) as realistic and rated the simulator as both acceptable (3.8/5) and feasible (3.8/5) for robotic surgical training. Conclusions Face validity, acceptability, and feasibility were established for the thoracic lobectomy module of the RobotiX Mentor simulator. Moderate evidence of construct validity was also demonstrated. With further work, this simulation module could help to reduce the initial part of the learning curve for trainees and decrease the risk of errors during live training.
Analysis of achieving an “ideal” outcome following midline unifocalization
Authors: Mainwaring Richard D , Patrick William L , Rosenblatt Tatiana R , Nasirov Teimour , Kamra Komal , Hanley Frank L 
Published: November 2018

Objective Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries is a complex form of congenital heart disease. Midline unifocalization has been developed for the surgical treatment of this condition. There are 3 outcome measures that determine long-term success: patients are alive, patients have achieved complete repair (i.e. ventricular septal defect closure), and patients have a relatively low right ventricle-to-aortic pressure ratio (<0.45). However, to date, no studies have combined these 3 outcome measures to analyze the likelihood of achieving an ideal outcome. Methods This was a retrospective review of 255 patients who underwent midline unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. The median age at unifocalization was 4.5 months. Results Two hundred thirty-five (92%) patients were alive at a mean follow-up of 5.3 years. Two hundred and seventeen (85%) patients underwent single-stage complete repair, and 38 (15%) had an initial unifocalization and shunt. Twenty-four of the 38 palliated patients have subsequently undergone repair. Thus 241 (94%) patients ultimately achieved complete repair. Of the 241 patients who were repaired, 219 (86%) had a right ventricle-to-aortic peak systolic pressure ratio <0.45. Combining these outcome measures, 77% of patients achieved an ideal outcome at one month, 73% at 6 months, 76% at one year, and 80% at 4 years. Conclusions Most (80%) patients can achieve all 3 measures of favorable outcome at 4 years following midline unifocalization. We speculate that this will be a favorable portend for the future of these patients.
Geographical variations in the use of diagnostic imaging of musculoskeletal diseases in Norway
Authors: Gransjøen Ann Mari , Lysdahl Kristin Bakke , Hofmann Bjørn Morten 
Published: November 2018

Background There is a high prevalence of musculoskeletal disorders in the Norwegian population. A significant number of these patients are referred to diagnostic imaging. Geographical variations in the use of imaging for musculoskeletal disorders may display over- or underuse, and knowledge about these variations is required. Purpose To investigate geographical variations in diagnostic imaging of the musculoskeletal system and analyze variations in the use of these examinations of all musculoskeletal diagnostic imaging, the specific modalities, and specific examinations. Material and Methods Population rates from Statistics Norway and outpatient radiological procedures of the musculoskeletal system registered at the Norwegian Health Economics Administration (HELFO) the first half of 2016 were accessed. The HELFO data were age-adjusted; high/low ratios were calculated as rates in number of examinations per 1000 inhabitants. A high/low ratio of 1 = equal use, 1.5–1.9 = moderate variation (approximately 50% difference), and > 2 (twice as much) = high variation. Results Geographical variations were demonstrated at all levels, with an overall high/low ratio of 1.3. For specific modalities the highest variation was for ultrasound (3.2) and CT (2.2). For individual examinations, the highest high/low ratios were observed for MRI of the shoulder (2.4) and radiography of the lower back (1.9) and shoulder (1.8). Conclusion We demonstrate a moderate to high geographical variation in the use of diagnostic imaging of the musculoskeletal system. This variation can indicate over- or underuse, which may violate basic principles of equity, priority, setting and appropriate care, and needs further attention.
Outcomes of medically managed patients with myocardial infarction
Authors: Kaul Padma , Savu Anamaria , Hamza Shereen , Knudtson Merril L , Bainey Kevin , Brass Neil , Armstrong Paul W , Welsh Robert C 
Published: November 2018

Aims: The purpose of this study was to compare outcomes associated with medical management of ST-elevation myocardial infarction and non-ST-elevation myocardial infarction patients presenting to hospitals with and without onsite catheterization facilities. Methods All patients ( n=25,921) with ST-elevation myocardial infarction ( n=10,563) or non-ST-elevation myocardial infarction ( n=15,358) in Alberta, Canada between April 2010–March 2016 were categorized according to availability of catheterization facilities at the hospital they presented to and their management strategy (medically managed without coronary angiography or medically managed after coronary angiography). Results: Overall, 51% presented to hospitals without catheterization facilities; and 34% were managed medically (18% without coronary angiography, and 16% after coronary angiography). Rates of medical management were higher at hospitals without versus those with catheterization facilities (43% vs. 24%, p<0.01). However, both the rate of presentation to hospitals without catheterization facilities (70% non-ST-elevation myocardial infarction, 24% ST-elevation myocardial infarction, p<0.01) and medical management (45% non-ST-elevation myocardial infarction, 18% ST-elevation myocardial infarction, p<0.01) differed by myocardial infarction type. The lack of catheterization facilities at the presenting hospital had no association with in-hospital mortality in patients medically managed without coronary angiography, but was associated with a lower risk of mortality among patients medically managed after coronary angiography. However, the latter benefit was restricted to non-ST-elevation myocardial infarction patients only (adjusted hazard ratio 0.43, 95% confidence interval: 0.25–0.76). Conclusion: The availability of catheterization facilities at the hospital at which non-ST-elevation myocardial infarction and ST-elevation myocardial infarction patients presented influenced their likelihood of being medically managed, but was not associated with adverse short- or long-term mortality outcomes.
Who should get long-term anticoagulant therapy for venous thromboembolism and with what?
Authors: Rodger Marc Alan , Le Gal Gregoire 
Published: November 2018

AbstractAfter an initial 3 to 6 months of anticoagulation for venous thromboembolism (VTE), clinicians and patients face an important question: “Do we stop anticoagulants or continue them indefinitely?” The decision is easy in some scenarios (eg, stop in VTE provoked by major surgery). In most scenarios, which are faced on a day-to-day basis in routine practice, it is a challenging decision because of uncertainty in estimates in the long-term risks (principally major bleeding) and benefits (reducing recurrent VTE) and the tight trade-offs between them. Once the decision is made to continue, the next question to tackle is “Which anticoagulant?” Here again, it is a difficult decision because of the uncertainty with regard to estimates of efficacy and the safety of anticoagulant options and the tight trade-offs between choices. We conclude with the approach that we take in our clinical practice.
Long-term mental health outcomes after unintentional burns sustained during childhood: a retrospective cohort study
Authors: Duke Janine M. , Randall Sean M. , Vetrichevvel Thirthar P. , McGarry Sarah , Boyd James H. , Rea Suzanne , Wood Fiona M. 
Published: November 2018

Abstract

Background
Burns are a devastating injury that can cause physical and psychological issues. Limited data exist on long-term mental health (MH) after unintentional burns sustained during childhood. This study assessed long-term MH admissions after paediatric burns.

Methods
This retrospective cohort study included all children (&lt; 18 years) hospitalised for a first burn (n = 11,967) in Western Australia, 1980–2012, and a frequency matched uninjured comparison cohort (n = 46,548). Linked hospital, MH and death data were examined. Multivariable negative binomial regression modelling was used to generate incidence rate ratios (IRR) and 95% confidence intervals (CI).

Results
The burn cohort had a significantly higher adjusted rate of post-burn MH admissions compared to the uninjured cohort (IRR, 95% CI: 2.55, 2.07–3.15). Post-burn MH admission rates were twice as high for those younger than 5 years at index burn (IRR, 95% CI 2.06, 1.54–2.74), three times higher for those 5–9 years and 15–18 years (IRR, 95% CI: 3.21, 1.92–5.37 and 3.37, 2.13–5.33, respectively) and almost five times higher for those aged 10–14 (IRR, 95% CI: 4.90, 3.10–7.76), when compared with respective ages of uninjured children. The burn cohort had higher admission rates for mood and anxiety disorders (IRR, 95% CI: 2.79, 2.20–3.53), psychotic disorders (IRR, 95% CI: 2.82, 1.97–4.03) and mental and behavioural conditions relating to drug and alcohol abuse (IRR, 95% CI: 4.25, 3.39–5.32).

Conclusions
Ongoing MH support is indicated for paediatric burn patients for a prolonged period after discharge to potentially prevent psychiatric morbidity and associated academic, social and psychological issues.
Young key affected population in Myanmar: are there any challenges in seeking information and care for HIV/sexually transmitted infections and reproductive health?
Authors: Htut Kyaw Min , Mon Myo Myo , Aye Zin Mar , Ni Lwin Lwin 
Published: November 2018

Background: Unmet needs and barriers in seeking HIV/STI and RH information and care are present especially among young key affected population (YKAP). Therefore, the study was conducted to determine the health seeking behaviors of YKAP regarding HIV/STI and RH, and challenges in seeking health information and care. Methods: A cross-sectional, mixed-methods study was conducted at two large cities in Myanmar. Face-to-face interviews were conducted with YKAP aged 15-24 years. In-depth interviews and key informant interviews were done with YKAP and health care providers. Descriptive statistics and bivariate analyses were done for quantitative data and thematic analysis was applied for qualitative data. Results: A total of 119 young men who have sex with men (YMSM) and 123 young female sex workers (YFSW) included in the study. Mean age of YMSM and YFSW were 20.9±2.4 and 21.7±2.2 years. Over 30% of YMSM and 49.3% of YFSW had experience of any STI symptom. Particularly, 17% of YMSM and 10% of YFSW had genital ulcer, and majority sought health care at NGO clinics. About 37% of YMSM and 40% of YFSW visited Drop-in-center (DIC) within one to six months. Over 13% of YMSM and 14.6% of YFSW had challenges in seeking HIV/STI and RH information. YMSM/YFSW type and age of YMSM were associated with visit to DIC. Lesser proportions of Tha-nge (43.5%), younger age YMSM (66.7%), brothel-based YFSW (47.9%) visited DIC than others (p<0.05). Challenges and unmet needs expressed by YKAP were reluctance in asking health information, worry for future fertility, consequences of anal sex and contraception. Challenges expressed by providers were limited time during outreach service and difficulty in reaching entertainment-based sex workers. Conclusions: Special attention in provision of health information should be paid to YKAP since there is a considerable proportion of YKAP with unmet need in seeking HIV/STI/RH information and care.
Spices for Thought: Salt, Chili Pepper, and Slaves in Ethiopian Amharic Proverbs
Authors: Salamon Hagar 
Published: November 2018

Abstract
Even though slavery-related understandings are deeply embedded in the collective Ethiopian consciousness, they are seldom explicitly discussed. In the course of oral interviews carried out in rural northwestern Ethiopia with elderly men and women who still recall the practice of slavery, a rich corpus of Amharic proverbs related to this topic was collected. Focusing on a specific segment of this corpus, I invite the reader to visit Ethiopian folkloric crossroads of slaves and salt, spiced up with some hot chili pepper. These proverbs are revealed as a powerful channel to tap into generally submerged and rarely discussed local slavery-related perceptions.