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Seventy-four revision stapedectomies performed consecutively over 10 years (1986 to 1995) were reviewed retrospectively. The most common intraoperative findings were incus erosion, prosthesis displacement, and oval window closure. Incus erosion was more frequently associated with multiple revisions. The postoperative results were reported using the conventional method (postoperative air minus preoperative bone) as well as the guidelines recently published by the American Academy of Otolaryngology--Head and Neck Surgery (postoperative air minus postoperative bone), with success rates of postoperative air-bone gap closure to within 10 dB after revision surgery of 51.6% and 45.6%, respectively. Patients with persistent conductive hearing loss (large residual air-bone gaps) after primary stapedectomy had poorer postrevision hearing results. Sensorineural hearing loss (defined as a drop in bone pure-tone average of more than 10 dB) occurred in four cases (5.4%). The number of revision surgeries, variations in operative techniques using laser or drill, and the ossicle to which the prosthesis was attached did not statistically affect the postoperative air-bone gaps. These results were compared with previously published data. [ABSTRACT FROM AUTHOR]

Importance: Previous studies on alcohol consumption and incident gout have mostly included men or combined both sexes, and the sex-specific associations between alcohol consumption and gout are poorly understood., Objective: To evaluate the consumption of total and specific alcoholic beverages in association with incident gout in men and women., Design, Setting, and Participants: This prospective cohort study included 401 128 participants in the UK Biobank aged 37 to 73 years who were free of gout at baseline (2006-2010). Participants were followed up through December 31, 2021, and data were analyzed between August 2023 and June 2024., Exposure: Questionnaire-based consumption of total alcohol and specific alcoholic beverages., Main Outcomes and Measures: The outcome was incident gout, identified using hospital records. Multivariable Cox proportional hazards regression models were used to estimate sex-specific hazard ratios (HRs) and 95% CIs of incident gout associated with alcohol consumption, with a particular consideration of reverse causation bias., Results: The main analysis included 179 828 men (mean [SD] age, 56.0 [8.2] years) and 221 300 women (mean [SD] age, 56.0 [8.0] years). Current drinkers showed a higher risk of gout than never drinkers among men (HR, 1.69; 95% CI, 1.30-2.18) but not among women (HR, 0.83; 95% CI, 0.67-1.03). Among current drinkers, higher total alcohol consumption was associated with a higher risk of gout among both sexes and more strongly among men than women (men: HR, 2.05 [95% CI, 1.84-2.30]; women: HR, 1.34 [95% CI, 1.12-1.61]). The most evident sex difference in the consumption of specific alcoholic beverages was observed for beer or cider (men: mean [SD], 4.2 [4.8] pints per week; women: mean [SD], 0.4 [1.1] pints per week). Consumption of champagne or white wine, beer or cider, and spirits each was associated with a higher risk of gout among both sexes, with beer or cider showing the strongest association per 1 pint per day (men: HR, 1.60 [95% CI, 1.53-1.67]; women: HR, 1.62 [95% CI, 1.02-2.57]). Some inverse associations between light to moderate consumption of specific alcoholic beverages and gout were eliminated after adjusting for other alcoholic beverages and excluding individuals who had reduced alcohol consumption for health reasons, self-reported poor health, or had cardiovascular disease, cancer, or kidney failure at baseline, or developed gout within the first 2 years of follow-up., Conclusions and Relevance: In this cohort study, higher consumption of several specific alcoholic beverages was associated with a higher risk of gout among both sexes. The sex-specific associations for total alcohol consumption may be associated with differences between men and women in the types of alcohol consumed.

Context: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases., Objective: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women., Methods: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders., Results: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99)., Conclusion: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objective: To examine the associations between microvascular disease (MVD) and risk of stroke, dementia, and their major subtypes among individuals with type 2 diabetes mellitus (T2DM)., Methods: We included 26,173 participants with T2DM from the UK Biobank who had no known stroke or dementia at baseline. MVD burden was reflected by the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. Cox regression models were used to estimate hazard ratios (HRs) and 95 % confidential intervals (CIs) of stroke and dementia associated with overall MVD burden and individual MVD., Results: During a median follow-up of 11.5 years, 1103 incident stroke (964 ischemic and 269 hemorrhagic stroke) and 813 incident dementia (312 Alzheimer's disease and 304 vascular dementia) cases were identified. The risk of stroke, dementia, and their major subtypes all increased with an increasing number of MVD (all P-trend <0.001). The adjusted HRs (95 % CIs) comparing three with no MVD were 5.03 (3.16, 8.02) for all stroke, 4.57 (2.75, 7.59) for ischemic stroke, and 6.60 (2.65, 16.43) for hemorrhagic stroke. The corresponding estimates were 4.28 (2.33, 7.86) for all-cause dementia, 6.96 (3.02, 16.01) for Alzheimer's disease, and 3.81 (1.40, 10.42) for vascular dementia. Among the three MVD, chronic kidney disease showed the strongest associations with both stroke subtypes, while peripheral neuropathy was most strongly associated with both dementia subtypes., Conclusions: Risk of stroke, dementia, and their major subtypes increased with an increasing number of MVD. The associations of individual MVD with stroke and dementia varied substantially by types of MVD., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background : A healthy eating pattern characterized by a higher intake of healthy plant foods has been associated with a lower risk of premature mortality, but whether this applies to individuals with varying glycemic status remains unclear. Methods : This study included 4621 participants with diabetes and 8061 participants with prediabetes from the US National Health and Nutrition Examination Survey (2007-2016). Using the dietary data assessed by two 24 h dietary recalls, a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) were created based on 15 food groups and were assessed for their relationships with mortality risk. Results : Over a median follow-up of 7.2 years, there were 1021 deaths in diabetes and 896 deaths in prediabetes. A higher hPDI (highest vs. lowest quartile) was associated with a 41% (HR = 0.59, 95% CI: 0.49-0.72; P -trend < 0.001) lower risk of all-cause mortality in diabetes and a 31% (HR = 0.69, 95% CI: 0.55-0.85; P -trend < 0.001) lower risk in prediabetes. A higher uPDI was associated with an 88% (HR = 1.88, 95% CI: 1.55-2.28; P -trend < 0.001) higher risk of mortality in diabetes and a 63% (HR = 1.63, 95% CI: 1.33-1.99; P -trend < 0.001) higher risk in prediabetes. Mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.0% to 10.9% of the relationships between hPDI or uPDI and all-cause mortality among participants with diabetes. Conclusions : For adults with diabetes as well as those with prediabetes, adhering to a plant-based diet rich in healthier plant foods is associated with a lower mortality risk, whereas a diet that incorporates less healthy plant foods is associated with a higher mortality risk.

Background: Sex differences exist in the prevalence of microvascular disease (MVD) and healthy-lifestyle adherence. Whether MVD and healthy lifestyles are associated with mortality risk similarly for women and men who have type 2 diabetes mellitus (T2DM) remains unknown., Methods: The present study included 9992 women and 15,860 men with T2DM from the UK Biobank. MVDs included retinopathy, peripheral neuropathy, and chronic kidney disease. Healthy lifestyle factors consisted of ideal BMI, nonsmoking, healthy diet, regular exercise, and appropriate sleep duration. Sex-specific hazard ratios (HRs) of mortality associated with the MVDs or healthy lifestyles were calculated and women-to-men ratio of HRs (RHR) were further estimated, after multivariable adjustment for potential confounders., Results: During a median of 12.7 years of follow-up, 4346 (1202 in women) all-cause and 1207 (254 in women) CVD deaths were recorded. The adjusted HRs (95% CI) of all-cause mortality for 1 additional increment of the MVDs were 1.71 (1.55, 1.88) for women and 1.48 (1.39, 1.57) for men, with an RHR of 1.16 (1.03, 1.30). The corresponding RHR was 1.36 (1.09, 1.69) for cardiovascular mortality. Adhering to a healthy lifestyle (≥4 vs. ≤1 lifestyle factor) was associated with an approximately 60%-70% lower risk of all-cause and cardiovascular mortality without sex differences (P-interaction >0.70). Furthermore, as compared with having no MVD and an unfavorable lifestyle, having ≥2 MVDs but a favorable lifestyle was not associated with a higher risk of all-cause mortality either in women (HR = 0.88; 95% CI: 0.49, 1.60) or in men (HR = 0.95; 95% CI: 0.64, 1.40), similarly when considering cardiovascular mortality., Conclusions: In T2DM, while MVDs are more strongly associated with mortality risk in women than in men, adhering to a favorable lifestyle is associated with a substantially lower risk of mortality and may eliminate the detrimental impact of MVDs in both sexes., Competing Interests: Conflict of interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Wide phthalate exposure has been associated with both declines in renal function and an elevated risk of mortality. Whether phthalate-associated risk of premature mortality differs by renal function status remains unclear., Methods: This study included 9605 adults from the U.S. National Health and Nutrition Examination Survey. Urinary concentrations of 11 phthalate metabolites were assessed using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. According to estimated glomerular filtration rate (eGFR), participants were grouped as having normal or modestly declined renal functions, or chronic kidney disease (CKD). Multivariable Cox regression models estimated all-cause mortality associated with phthalate exposure, overall and by renal function status., Results: Overall, Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and Mono-(2-ethyl-5-carbox-ypentyl) phthalate (MECPP) were associated with an elevated risk of mortality (P-trend across tertile <0.05). Moreover, significant interactions were observed between eGFR and MEHHP, MEOHP, MECPP, DEHP in the whole population (P for interactions <0.05). After stratification by renal function, total Di (2-ethylhexyl) phthalate (DEHP) was additionally found to be associated with mortality risk in the CKD group (HR = 1.12; 95% CI: 1.01, 1.25). Co-exposure to the 11 phthalate metabolites was associated with a higher risk of all-cause mortality in the CKD (HR = 1.47; 95% CI: 1.18, 1.84) and modestly declined renal function group (HR = 1.25; 95% CI: 1.09, 1.44)., Conclusions: The associations between phthalate exposure and risk of all-cause mortality were primarily observed in CKD patients, reinforcing the need for monitoring phthalate exposure in this patient population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

Background: Venetoclax in combination with hypomethylating agents (HMAs) is standard-of-care in patients with newly diagnosed acute myeloid leukemia (AML) who are ≥ 75 years old or unfit for intensive chemotherapy. We examined early real-world treatment experience among patients with AML receiving venetoclax+HMAs or HMA monotherapy., Patients and Methods: This retrospective cohort study used an electronic health record-derived, deidentified, United States nationwide database comprised of patient-level structured and unstructured data, curated via technology-enabled abstraction. Patients with an AML diagnosis on or after January 1, 2014, who had ≥ 2 clinic visits, and initiated treatment with venetoclax+HMAs from June 1, 2018 to March 31, 2021, or HMA monotherapy from January 1, 2016 to May 31, 2018, were included. Kaplan-Meier analysis was used to estimate time to last administration (TTLA) and overall survival (OS)., Results: Overall, 619 patients treated with venetoclax+HMAs and 480 treated with HMA monotherapy were selected from the database. Median age at diagnosis was 76 and 78 years, respectively, most patients were treated in community practice (83.4% and 89.4%, respectively), and almost half had secondary AML (47.2% and 47.3%, respectively). Adjusted analyses showed both significantly longer TTLA (3.6 months vs. 2.3 months; hazard ratio [HR] = 0.69 [95% confidence interval (CI), 0.60-0.80], P< .0001) and OS (9.3 months vs. 5.9 months; HR = 0.71 [95% CI, 0.61-0.82], P < .0001) in patients treated with venetoclax+HMAs versus HMA monotherapy, respectively., Conclusion: This study shows benefit in real-world outcomes of venetoclax+HMAs relative to HMA monotherapy in patients with newly diagnosed AML, using a predominantly community-based database., Competing Interests: Disclosure AG, EM, MM, KN, GK: Genentech, Inc (E); F. Hoffmann-La Roche Ltd (OI). TX, EMF: F. Hoffmann-La Roche Ltd (E/OI). WWHC: AbbVie, Inc (E) VK: Incyte, Inc. (RF); Pfizer, Inc., Novartis, Inc (C/A). DRG: Genentech, Inc./F. Hoffmann-La Roche Ltd (C/A); ADC Therapeutics, Jazz Pharmaceuticals, Genentech, Inc./F. Hoffmann-La Roche Ltd. (Other: speakers’ bureau); Bristol Myers Squibb (SAB)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We perform anatomical landmarking for craniomaxillofacial (CMF) bones without explicitly segmenting them. Toward this, we propose a simple, yet efficient, deep network architecture, called relational reasoning network (RRN), to accurately learn the local and the global relations among the landmarks in CMF bones; specifically, mandible, maxilla, and nasal bones., Approach: The proposed RRN works in an end-to-end manner, utilizing learned relations of the landmarks based on dense-block units. For a given few landmarks as input, RRN treats the landmarking process similar to a data imputation problem where predicted landmarks are considered missing., Results: We applied RRN to cone-beam computed tomography scans obtained from 250 patients. With a fourfold cross-validation technique, we obtained an average root mean squared error of < 2    mm per landmark. Our proposed RRN has revealed unique relationships among the landmarks that help us in inferring informativeness of the landmark points. The proposed system identifies the missing landmark locations accurately even when severe pathology or deformations are present in the bones., Conclusions: Accurately identifying anatomical landmarks is a crucial step in deformation analysis and surgical planning for CMF surgeries. Achieving this goal without the need for explicit bone segmentation addresses a major limitation of segmentation-based approaches, where segmentation failure (as often is the case in bones with severe pathology or deformation) could easily lead to incorrect landmarking. To the best of our knowledge, this is the first-of-its-kind algorithm finding anatomical relations of the objects using deep learning., (© 2023 The Authors.)

Aims: Inhibitor of soluble epoxide hydrolase (t-AUCB) has been used in the experimental therapy of hypertension. This study aimed to investigate whether the secretion of submandibular glands (SMGs) altered in renal hypertensive rats, and to explore whether t-AUCB could improve the salivary secretion., Main Methods: 2-kidney 1-clip Sprague-Dawley rats were used as renal hypertensive animals. t-AUCB treatment was given for 1 week after 8 weeks modeling. Blood pressure, blood perfusion and the secretion of SMGs, and endothelium-dependent relaxation of external maxillary artery were measured to investigate the effects of t-AUCB on the vascular tone and the secretion of SMGs in renal hypertensive rats. SMGs were collected for histological evaluation and the internal arteries were dissected for primary endothelial cells culture., Key Findings: The blood perfusion and flow rate of SMGs in the renal hypertensive rats were significantly lower than those in the controls. Endothelium-dependent relaxation of the external maxillary artery and AMPK/Akt/eNOS signaling was impaired in hypertensive rats. The glandular morphology and the concentration of salivary ions did not change obviously. t-AUCB treatment ameliorated the secretion of SMGs, the blood perfusion, and the dysfunction of endothelium-dependent relaxation of the external maxillary artery by activating the AMPK/Akt/eNOS pathway in hypertensive rats., Significance: t-AUCB increases the blood perfusion through ameliorating dysfunction of endothelium-dependent relaxation of SMGs arteries and thus improves the hyposecretion of SMGs in hypertensive rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the effect of topical glucocorticoid in treating phimosis on urinarytract infection(UTI) of vesicoureteral reflux(VUR) in infants. Methods: Clinical data of infants with UTI diagnosed as primary VUR admitted to our hospital from January 2016 to January 2021 were retrospectively analyzed. The children were divided into three groups:the effective group (topical glucocorticoid was effective in the treatment of phimosis), the ineffective group(topical glucocorticoid was ineffective in the treatment of phimosis), and the untreated group(phimosis was not treated). Age of onset, degree of reflux, side and other indicators were compared to understand the effectiveness of topical glucocorticoid in treating phimosis, and the clinical characteristics of repeated UTI with VUR in treated phimosis and untreated phimosis. Results: A total of 544 children were included. Among them, 59 cases were treated with topical glucocorticoid for phimosis, 48 cases in the effective group, and their age was (12.5±8.4) months;11 cases in the ineffective group,and their age was (11.2±8.9) months. There were 485 cases in the untreated group, and their age was (13.1±9.3) months.The effective rate of topical glucocorticoid in the treatment of phimosis was 81.36%. There were 12 cases(12/48) of recurrent UTI in the effective group and 213 cases (213/485)of recurrent UTI in the untreated group, and the difference between the two groups was statistically significant ( P =0.008). Conclusion: Treatment of phimosis with topical glucocorticoid is an effective, easy to perform, and cost-effective method, and can effectively reduce the risk of recurrent UTI in infants with primary VUR.

Background: A country's health system faces pressure when hit by an unexpected shock, such as what we observe in the midst of the coronavirus disease 2019 (COVID-19) pandemic. The concept of resilience is highly relevant in this context and is a prerequisite for a health system capable of withstanding future shocks. By exploring how the key dimensions of the resilient health system framework are applied, the present systematic review synthesizes the vital features of resilient health systems in low- and middle-income countries. The aim of this review is to ascertain the relevance of health system resilience in the context of a major shock, through better understanding its dimensions, uses and implications., Methods: The review uses the best-fit framework synthesis approach. An a priori conceptual framework was selected and a coding framework created. A systematic search identified 4284 unique citations from electronic databases and reports by non-governmental organisations, 12 of which met the inclusion criteria. Data were extracted and coded against the pre-existing themes. Themes outside of the a priori framework were collated to form a refined list of themes. Then, all twelve studies were revisited using the new list of themes in the context of each study., Results: Ten themes were generated from the analysis. Five confirmed the a priori conceptual framework that capture the dynamic attributes of a resilient system. Five new themes were identified as foundational for achieving resilience: realigned relationships, foresight and motivation as drivers, and emergency preparedness and change management as organisational mechanisms., Conclusion: The refined conceptual model shows how the themes inter-connect. The foundations of resilience appear to be critical especially in resource-constrained settings to unlock the dynamic attributes of resilience. This review prompts countries to consider building the foundations of resilience described here as a priority to better prepare for future shocks., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Muscular dystrophy (MD) causes muscle wasting and is often lethal in patients due to a lack of proven therapies. In contrast, mouse models of MD are notoriously mild. We have previously shown severe human-like muscle pathology in mdx [Duchenne MD (DMD)] and dysferlin-deficient limb-girdle MD type 2B (LGMD2B) mice by inactivating the gene encoding for apolipoprotein E (ApoE), a lipid transporter synthesized by the liver, brain and adipocytes to regulate lipid and fat metabolism. Having recently established that human DMD is a novel type of primary genetic dyslipidaemia with elevated cholesterol, we sought to determine whether cholesterol could exacerbate the muscle wasting process observed in severe rodent MD., Methods: Severe mdx and dysferlin knock-out mice lacking ApoE were treated with ezetimibe (15 mg/kg/day), a clinically approved drug exhibiting few pleiotropic effects. In separate studies, dietary cholesterol was raised (from 0.2% to 2% cholesterol) in combination with experimental micro-injury and direct cholesterol injection assays. Muscles were assessed histologically for changes in collagen and adipocyte infiltration and both transcriptomic and cellular changes by RNA-seq and fluorescence-activated cell sorting analysis., Results: Treatment of severe DMD and LGMD2B mice with ezetimibe completely prevented clinical signs of ambulatory dysfunction (0% incidence vs. 33% for vehicle treatment; P < 0.05). Histological analyses revealed that ezetimibe-reduced fibro-fatty infiltration up to 84% and 63% in severely affected triceps (P ≤ 0.0001) and gastrocnemius (P ≤ 0.003) muscles, resulting in a respective 1.9-fold and 2.2-fold retention of healthy myofibre area (P ≤ 0.0001). Additionally, raising dietary cholesterol and thus concentrations of plasma low-density lipoprotein-associated cholesterol (by 250%; P < 0.0001) reduced overall survivability (by 100%; P < 0.001) and worsened muscle damage in the LGMD2B triceps by 767% (P < 0.03). Micro-pin-induced mechanical injury in LGMD2B mice fed a high cholesterol diet exacerbated muscle damage by 425% (P < 0.03) and increased macrophage recruitment (by 98%; P = 0.03) compared with those injured on a chow diet. Parallel RNA-seq analyses revealed that injury in cholesterol-fed mice also modulated the expression of 3671 transcripts (1953 up-regulated), with fibrogenic, inflammatory and programmed cell death-associated pathways among the most enriched. Mice lacking dysferlin also displayed heightened muscle necrosis (by 123%; P < 0.0001) following a direct intramuscular injection of cholesterol compared with control mice., Conclusions: Cholesterol exacerbates rodent MD. Specific inhibition of cholesterol absorption with ezetimibe may safely attenuate human MD severity and delay death., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background/Aim: Essential oils of sunflower receptacles (SEOs) have antibacterial and antioxidant potential. However, the differences of biological activities from the different varieties of sunflowers have not been studied till now. The purpose of this study was to compare the differences of chemical compounds, antioxidant activities, and inhibitory activities against xanthine oxidase (XO) of SEOs from the three varieties of sunflowers including LD5009, SH363, and S606. Methods: SEOs were extracted by using the optimal extraction conditions selected by response surface methodology (RSM). Chemical compounds of SEOs were identified from the three varieties of sunflowers by gas chromatography-mass spectrometry (GC-MS). Antioxidant activities of SEOs were detected by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and iron ion reduction ability. Inhibitory activities of SEOs against XO were measured by using UV spectrophotometer. XO inhibitors were selected from the main chemical compounds of SEOs by the high-throughput selections and molecular simulation docking. Results: The extraction yields of SEOs from LD5009, SH363, and S606 were 0.176, 0.319, and 0.580%, respectively. A total of 101 chemical compounds of SEOs were identified from the three varieties of sunflowers. In addition, the results of inhibitory activities against XO showed that SEOs can reduce uric acid significantly. Eupatoriochromene may be the most important chemical compounds of SEOs for reducing uric acid. The results of antioxidant activities and inhibitory activities against XO showed that SEOs of LD5009 had the strongest antioxidant and XO inhibitory activities. The Pearson correlation coefficient ( r > 0.95) showed that γ-terpinene, (E)-citral, and L-Bornyl acetate were highly correlated with the antioxidant activities and XO inhibitory ability. Conclusion: SEOs had antioxidant activities and XO inhibitory ability. It would provide more scientific information for utilization and selection of varieties of sunflowers, which would increase the food quality of sunflowers and incomes of farmers., Competing Interests: The authors declare that this study received funding from Jilin Teyi Food Technology Corporation Ltd. The funder had the following involvement in the study: design, sample collection and the decision to submit it for publication., (Copyright © 2021 Liu, Gao, Dong, Qiao, Yan, Han, Li and Han.)

Objective: The association between benign paroxysmal positional vertigo (BPPV) and impaired calcium metabolism has attracted widespread interest. Several studies have suggested that decreased bone mineral density (BMD) and serum 25-hydroxyvitamin D (25(OH)D) level are related to the occurrence and/or recurrence of BPPV; however, the characteristics of bone metabolism in patients with BPPV subtypes have not been fully investigated, and conclusions have been controversial. This study aimed to evaluate BMD and serum levels of 25(OH)D and bone turnover markers to clarify the characteristics of bone metabolism in patients with different types of BPPV., Method: We retrospectively analysed the data of new-onset idiopathic postmenopausal female patients with BPPV at our institution from January 2016 to January 2020. The patients' demographic data including age, medication history, concomitant diseases, onset time, clinical form, laboratory indicators, such as serum levels of 25(OH)D, bone formation markers, namely, amino-terminal propeptide of type I procollagen (PINP) and osteocalcin (OC), bone resorption marker, namely, β-isomerized carboxy-terminal telopeptide of type I collagen (β-CTX), and BMD were collected and analysed., Results: This study included 201 consecutive postmenopausal female patients with BPPV. Among them, 138 were diagnosed with posterior semicircular canal BPPV, 42 were diagnosed with lateral semicircular canal canalolithiasis, and 21 were diagnosed with lateral semicircular canal cupulolithiasis. There were no significant differences in age distribution, body mass index, clinical history, levels of albumin, globulin, uric acid, creatinine, or blood urea nitrogen, lipid profiles (except high-density lipoprotein cholesterol) and routine blood parameters among these groups (P > 0.05). There were no significant differences in the mean T-score and BMD values of different sites or in the serum levels of 25(OH)D and bone turnover markers (PINP, OC and β-CTX) among the subgroups (P > 0.05). The proportion of reduction in BMD (T-score < -1 SD) and decreased serum vitamin D level (< 20 ng/ml) were not significantly different between the subgroups (P > 0.05)., Conclusion: There were no significant differences in bone metabolism in postmenopausal female patients with different types of idiopathic BPPV., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Antimicrobial resistance (AMR) is a growing global health problem. Staphylococcus aureus ( SA ) is a common bacterium associated with a variety of community and hospital infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounts for most SA related morbidity and mortality. In this study, we determined the prevalence and factors associated with SA and MRSA in Myanmar., Methods: We collected the data retrospectively by reviewing an electronic register containing the results of bacterial culture and antibiotic susceptibility testing of biological specimens received from healthcare facilities during 2018-2019., Results: Of the 37,798 biological specimens with bacterial culture growth, 22% (8244) were Gram-positive. Among the Gram-positive bacteria, 42% (2801) were SA , of which 48% (1331) were judged as MRSA by phenotypic methods. The prevalence of MRSA was higher in the older age groups, in female patients, in urine specimens and specimens received from the intensive care unit and dermatology departments. One site (Site F) had the highest MRSA prevalence of the seven AMR sentinel sites. Most SA isolates were sensitive to vancomycin (90%) by phenotypic methods., Conclusions: The high prevalence of MRSA indicates a major public health threat. There is an urgent need to strengthen the AMR surveillance and hospital infection control program in Myanmar.

Globally, antibiotic resistance in bacteria isolated from neonatal sepsis is increasing. In this cross-sectional study conducted at a medical college teaching hospital in Nepal, we assessed the antibiotic resistance levels in bacteria cultured from neonates with sepsis and their in-hospital treatment outcomes. We extracted data of neonates with sepsis admitted for in-patient care from June 2018 to December 2019 by reviewing hospital records of the neonatal intensive care unit and microbiology department. A total of 308 neonates with sepsis were admitted of which, blood bacterial culture antibiotic sensitivity reports were available for 298 neonates. Twenty neonates (7%) had bacteriologic culture-confirmed neonatal sepsis. The most common bacterial species isolated were Staphylococcus aureus (8), followed by coagulase-negative Staphylococcus (5). Most of these bacteria were resistant to at least one first-line antibiotic used to manage neonatal sepsis. Overall, there were 7 (2%) deaths among the 308 neonates (none of them from the bacterial culture-positive group), and 53 (17%) neonates had left the hospital against medical advice (LAMA). Improving hospital procedures to isolate bacteria in neonates with sepsis, undertaking measures to prevent the spread of antibiotic-resistant bacteria, and addressing LAMA's reasons are urgently needed.

We aimed to assess the clinicopathological features and to determine the prognostic factors of cervical adenocarcinoma (AC). Relevant data were extracted from surveillance, epidemiology and end results database from 2004 to 2015. The log-rank test and Cox proportional hazard analysis were subsequently utilized to identify independent prognostic factors. A total of 3102 patients were identified. The enrolled patients were characterized by higher proportion of early FIGO stage (stage I: 65.9%; stage II: 14.1%), low pathological grade (grade I/II: 49.1%) and tumor size ≤ 4 cm (46.8%). The 5- and 10-year cancer-specific survival rates of these patients were 74.47% and 70.00%, respectively. Meanwhile, the 5- and 10-year overall survival (OS) rates were 71.52% and 65.17%, respectively. Multivariate analysis revealed that married status, surgery as well as chemotherapy were independent favorable prognostic indicators. Additionally, aged > 45, tumor grade III/IV, tumor size > 4 cm, advanced FIGO stage and pelvic lymph node metastasis (LNM) were unfavorable prognostic factors (all P < 0.01). Stratified analysis found that patients without surgery could significantly benefit from chemotherapy and radiotherapy. In addition, chemotherapy could significantly improve the survival in stage II-IV patients and radiotherapy could only improve the survival in stage III patients (all P < 0.01). Marital status, age, grade, tumor size, FIGO stage, surgery, pelvic LNM and chemotherapy were significantly associated with the prognosis of cervical AC.

A novel and efficient process has been developed for copper-catalyzed C(sp 3 )-H direct imidation of methyl sulfides with N -fluorobenzenesulfonimide(NFSI). Without using any ligands, various methyl sulfides including aromatic and aliphatic methyl sulfides, can be transformed to the corresponding N -((phenylthio)methyl)-benzenesulfonamide derivatives in good to excellent yields., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with an indolent course. It is less often reported as a second tumor that occurs after treatment of malignant tumors in pediatric patients. Here, we report a case of IMT following Wilms tumor (WT), and conduct a literature review concerning IMTs and WT to evaluate the diagnostic possibility of IMT as a second tumor. The coexistence of the 2 tumors may cause confusion as to whether they share genetic links or that IMTs may appear as late effects of the treatment of WT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Electronic Health (eHealth) is the use of information and communication technologies for health and plays a significant role in improving public health. The rapid expansion and development of eHealth initiatives allow researchers and healthcare providers to connect more effectively with patients. The aim of the CIH LMU Symposium 2020 was to discuss the current challenges facing the field, opportunities in eHealth implementation, to share the experiences from different healthcare systems, and to discuss future trends addressing the use of digital platforms in health. The symposium on eHealth explored how the health and technology sector must increase efforts to reduce the obstacles facing public and private investment, the efficacy in preventing diseases and improving patient quality of life, and the ethical and legal frameworks that influence the proper development of the different platforms and initiatives related to the field. This symposium furthered the sharing of knowledge, networking, and patient/user and practitioner experiences in low- and middle-income countries (LMIC) in both public and private sectors.

Purpose: To present the clinicopathological characteristics and outcome of children with bladder and ureteral inflammatory myofibroblastic tumors (IMTs) in our center., Methods: We reviewed the medical records of patients with bladder and ureteral IMTs from 2010 to 2018. We recorded patients' demographic data, presentation, hemoglobin level, presence of hydronephrosis, tumor size, treatment, and outcomes., Results: Eight patients with bladder IMTs and 3 with ureteral IMTs were treated at our center during this period. The mean age was 7.1 years. Four patients presented with anemia at diagnosis with the mean hemoglobin level 84.5 g/L. Among patients with bladder IMTs, 5 were male and 3 were female. The most common symptom was lower urinary symptoms in 6 patients, followed by hematuria in 4 patients. 2 patients had complications of hydronephrosis and hydroureter. Among patients with ureteral IMTs, 2 were male and one was female. The most common symptom was abdominal pain, and 3 patients presented with upper urinary tract dilation. All patients underwent surgery. A total of 81.8% were positive for anaplastic lymphoma kinase. Cytokeratin (CK) expression was present in all patients with bladder IMTs, while it was negative in 2 patients with ureteral IMTs. During mean follow-up of 43.4 months, all patients survived event-free., Conclusion: The presence of hydronephrosis and hydroureter is rare in patients with bladder IMTs. Anemia caused by hematuria should be raised the index of suspicion for IMTs. Children with bladder and ureteral IMTs had excellent prognosis. The expression pattern of CK varied between bladder and ureteral IMTs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The article "Long non-coding RNA ANCR promotes progression of NSCLC by inhibiting E-Ca expression, by T. Zhou, J.-J. Fang, Y.-X. Zhou, Z.-P. Li, L. Jiang, W.-W. Han, Z.-H. Zhu, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1250-1257-DOI: 10.26355/eurrev&#95;202002&#95;20178-PMID: 32096155" has been withdrawn from the authors. They stated that "during the last few months, new experimental data have been obtained and analyzed, so we want to rewrite the paper to further test the cell experiment and give more evidence to support our paper. It is difficult to repeat the part of the cell experiment, and the results need to be further improved. In addition, the internal reference pictures in the paper are wrong and need to be re experimented and modified. This needs more detailed studies and maybe a long time, so we want to withdraw our paper and resubmit it when it is ready". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20178.

Background: Globally, two billion workers are employed informally but there is limited research on the relationship between informal work and health. Existing studies have focused on informality as an employment condition, with little emphasis on the diversity of physical and social contexts in which informal work takes place. The study considers the diversity of informal workplaces and explores the ways in which this diversity might influence health and well-being of two informal occupational groups in Yangon, the former capital of Myanmar., Methods: We conducted 21 field observations and 47 semi-structured interviews with street vendors and home-based garment workers based in Yangon, Myanmar. A constant comparative method was used to identify and compare how the physical characteristics of their informal workplaces affect their health for these two informal subgroups., Results: Although both street vendors and home-based garment workers work informally, their exposure to occupational health and income risks are specific to the physical features of their informal workplaces. Street vendors, who work in public spaces with minimal coverage, are more likely to experience the direct effects of outdoor pollution, inclement weather and ergonomic risks from lifting, carrying and transporting heavy merchandise while home-based garment workers, many of whom live and work in unsanitary housing and deprived neighborhoods, are more likely to experience pollution in or near their homes, and ergonomic risks from poor posture. Similarly, although both groups face safety challenges, street vendors face urban violence and abuse during their commute and at vending points whereas home-based garment workers felt unsafe in their home-based workplaces due to the presence of crime and violence in their neighborhoods., Conclusion: While informal employment is universally characterized by lack of social protection, exposure to occupational health and income risks for subpopulations of informal workers is determined by the specific physical and social environments of their workplaces. Efforts to improve the health of informal workers should consider the contexts in which informal work takes place to develop tailored interventions for subpopulations of informal workers.

Background: The National Malaria Control Programme (NMCP) in Myanmar trained health staff at the township level starting in mid-2016 in order to achieve the Plasmodium falciparum malaria elimination target by 2020. This study aimed to evaluate the knowledge and perception of Basic Health Staff (BHS) and Vector-borne Diseases Control (VBDC) teams exposed to a short training course on malaria elimination in six targeted townships which included two conflict-affected townships between 2016 and 2017., Methods: This was a cross-sectional mixed-methods study using quantitative and qualitative data extracted from one survey database conducted between October 2018 and March 2019. Modified Poisson regression analysis was performed to ascertain the determinants of low knowledge scores after the training programme., Results: Altogether, 544 trained frontline health workers involved in malaria elimination at the time of the survey were recruited and 56% (302/544) were stationed at sub-Rural Health Centers. More than half of the respondents had correct knowledge of malaria case categories although relapse and recrudescent cases (39% and 37% respectively) were less well known. Over two-thirds of respondents could mention those eligible for malaria testing. Less than 30% knew the foci classification. The overall knowledge scores ranged from 10 to 31. The significant predictors of low level of knowledge [the cut-off point was set at the median value of 21 (IQR 12-30)] in multivariate analysis were the younger age group (18-29 years) and health staff who had attended malaria elimination training in 2017, [(APR = 1.6, 95% CI 1.2-2.2)]; and (APR = 1.5, 95%CI 1.2-1.8)]. Qualitative data from 10 key informants identified perceived challenges in conflict-affected areas as well as in areas of high population mobility with further implications for case surveillance. In addition, the low level of education of community members was noted as one of the barriers that hampered public readiness in the elimination scenario., Conclusion: A significant impact on knowledge improvement after the training programme was not visible especially for correct notification of malaria cases and treatment according to National Malaria Elimination Guidelines. Regular monitoring and continuing guidance by the higher level management is critical to support the field staff., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Objective: To observe the effect of the micro ribonucleic acid (miR)-10a on sepsis-induced liver injury in rats through the transforming growth factor-b1 (TGF-b1)/Smad signaling pathway., Materials and Methods: The rat model of sepsis was established via cecal ligation and puncture, in which miR-10a was overexpressed and silenced using liposome transfection. The rats were randomly divided into miR-10a mimics group (Mimics group, n=10) and miR-10a inhibitors group (Inhibitors group, n=10), and the sham operation group (Sham group, n=10) was also set up. The transfection efficiency of miR-10a in liver tissues in each group was detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), the serum liver function indexes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were determined. Moreover, the content of the serum reactive oxygen species (ROS), glutathione (GSH), and GSH peroxidase (GSH-Px) was determined using enzyme-linked immunosorbent assay (ELISA). The content of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) in liver tissues was detected, and the pathological changes in liver tissues were observed through hematoxylin-eosin (HE) staining. Finally, the expression levels of cytochrome P4502E1 (CYP2E1) and TGF-b1/Smad signaling pathway genes and proteins in liver tissues were detected via qRT-PCR and Western blotting., Results: The expression of miR-10a was significantly increased in Mimics group (p<0.05) and extremely low in the Inhibitors group (p<0.05). In Mimics group, the levels of serum AST, ALT, and LDH were significantly increased (p<0.05), the content of ROS, TNF-α, IL-6, and MPO was substantially increased (p<0.05), while that of GSH and GSH-Px notably declined (p<0.05). According to the HE staining results, the liver cells were orderly arranged in the Inhibitors group, and they were disorderly arranged with more inflammatory cells in the Mimics group. The results of the gene and protein assays showed that the expression levels of CYP2E1, TGF-b1, and Smad2 in Mimics group were markedly higher than those in the Sham group (p<0.05), while they displayed the opposite trends in the Inhibitors group (p<0.05)., Conclusions: Silencing miR-10a can inhibit the occurrence of sepsis-induced liver injury in rats by downregulating the TGF-β1/Smad pathway.

There is no cure or beneficial management option for Limb-Girdle muscular dystrophy (MD) type 2B (LGMD2B). Losartan, a blood pressure (BP) lowering angiotensin II (AngII) receptor type 1 (ATR1) blocker (ARB) with unique anti-transforming growth factor-β (TGF-β) properties, can protect muscles in various types of MD such as Duchenne MD, suggesting a potential benefit for LGMD2B patients. Herein, we show in a mild, dysferlin-null mouse model of LGMD2B that losartan increased quadriceps muscle fibrosis (142%; P<0.0001). In a severe, atherogenic diet-fed model of LGMD2B recently described by our group, losartan further exacerbated dysferlin-null mouse muscle wasting in quadriceps and triceps brachii, two muscles typically affected by LGMD2B, by 40% and 51%, respectively (P<0.05). Lower TGF-β signalling was not observed with losartan, therefore plasma levels of atherogenic lipids known to aggravate LGMD2B severity were investigated. We report that losartan increased both plasma triglycerides and cholesterol concentrations in dysferlin-null mice. Other protective properties of losartan, such as increased nitric oxide release and BP lowering, were also reduced in the absence of dysferlin expression. Our data suggest that LGMD2B patients may show some resistance to the primary BP-lowering effects of losartan along with accelerated muscle wasting and dyslipidemia. Hence, we urge caution on the use of ARBs in this population as their ATR1 pathway may be dysfunctional., Competing Interests: The authors have declared that no competing interests exist.

The present study aimed to explore the correlation between the dynamic serum levels of phospholipase A2 receptor (PLA2R), aldose reductase (AR) and superoxide dismutase 2(SOD2) antibodies with disease activity and treatment response in patients with idiopathic membranous nephropathy (IMN). The present study included 56 patients with IMN who were diagnosed through a renal biopsy and presenting with nephrotic syndrome. The patients were divided into two treatment groups: One treated with cyclophosphamide (CTX) and one with tacrolimus (FK506). Serum was collected prior to treatment, and at 1, 3, 6, 9 and 12 months after the start of the 12-month-long therapy. Samples were tested by ELISA to measure anti-PLA2R, anti-AR and anti-SOD2 antibody titers. In addition, urinary protein excretion, serum albumin (Alb) and other blood biochemical indexes were measured. Theanti-PLA2R antibody positivity rate was 71.43% in the patients prior to treatment. After 12 months of treatment, proteinuria and PLA2R antibody levels were decreased, whereas serum Alb was increased. There was no significant difference of remission rates between the CTX and FK506 groups. In conclusion, the results of the present study indicate that the anti-PLA2R antibody level is correlated with the severity of IMN, whereas anti-AR and anti-SOD2 antibody levels are not. In addition, there was no significant difference between the CTX and FK506 groups in regards to the remission rates of patients with IMN.

Objective: To investigate the relationship between serum 25-hydroxyvitamin D[25(OH) D] levels and idiopathic benign paroxysmal positional vertigo (BPPV) in female patients. Methods: A total of 67 women diagnosed with idiopathic BPPV were selected as the study group between January and December 2016 in Ningbo No.2 Hospital, and 95 healthy women without a history of vertigo or dizziness were selected as the control group. The data of height, weight, histories of hypertension and diabetes mellitus were collected, and serum 25(OH) D levels were measured. The number of the recurrence and canalith repositioning maneuvers were recorded during the one-year follow-up. Results: No significant differences of age, body mass index, histories of hypertension and diabetes mellitus between patients with BPPV and healthy controls (all P >0.05) .The serum 25 (OH) D levels were significantly lower in patients with idiopathic BPPV than in healthy controls [(50.56±13.36) nmol/L vs (56.55±16.21) nmol/L, t =-2.485, P =0.014]. BPPV patients with low level of 25(OH) D showed a significant increase in the number of canalith repositioning maneuvers required and the recurrence rate. The regression analyses demonstrated that 25(OH)D deficiency was associated with BPPV with an odds ratio of 2.054 (95% CI: 1.088-3.877, P =0.026). Conclusion: 25(OH) D deficiency may be a risk factor of BPPV.

Background: Myanmar National AIDS programme's priority is to improve the survival of all people living with HIV by providing anti-retroviral therapy (ART) care. More than 7200 children (aged <15 years) have been enrolled into ART care from 2005 to 2016. A previous study showed that ~11% children on ART care had either died or were lost to follow-up by 60 months. Factors associated with death and lost-to follow-up (adverse outcomes) have not been previously studied., Objectives: To describe the association between demographic and clinical characteristics at enrollment into ART care with adverse outcomes., Methods: Cohort study using records of children enrolled for ART care at Mingalardon Specialist Hospital (main Paediatric ART center in Myanmar) from 2006-2016. We used multivariable Cox proportional hazards regression models for analysis., Results: 1,159 children were enrolled for ART care and they contributed a total of 1.45 million person-days of follow-up period. 112 (10%) had an adverse outcome during the follow-up time period (55 deaths, 57 lost to follow-up). Enrollment into the ART care through in-patient care department of the hospital, CD4 Cell count <50/mm3, enrollment during changing ART guidelines (different ART eligibility criteria and preferred ART regimen) were independently associated with higher hazards of adverse outcome. Receiving protease inhibitor-based ART regimen at enrollment was independently associated with lower hazards of adverse outcome. Age, sex, residing in urban or rural areas, WHO clinical stage, having TB at the time of enrollment, receiving cotrimoxazole prophylaxis were not statistically associated with adverse outcomes., Conclusion: Our analysis reconfirms good survival of children on ART care (including those with TB). The characteristics associated with adverse outcomes (other than CD4 cell count<50) are surrogates of some unmeasured underlying health system/ patient related factors that needs further exploration to improve the survival of children on ART care.

Objective: To analyze the bone mineral density and serum osteocalcin levels in postmenopausal women with idiopathic benign paroxysmal positional vertigo. Methods: A total of 64 postmenopausal women with idiopathic BPPV were selected as the study group, and 98 postmenopausal healthy women were selected as the control group. Bone mineral density and serum osteocalcin levels were analyzed and compared between the groups.χ(2) test was used for numeration data and t test was used for measurement data. Results: The prevalence of osteoporosis or osteopenia in BPPV group 67.2% (43/64) was significantly higher than that in the control group 51.0% (50/98) (χ(2)=4.139, P =0.042). Among BPPV subjects, there was a negative correlation between osteocalcin and bone density T ( r =-0.469, P <0.001). Osteocalcin was found in normal bone mass subgroup (13.61±4.32)μg/L, decreased bone mass subgroup (17.49±7.61)μg/L, and osteoporosis subgroup (20.83±6.72)μg/L, respectively, and the difference was statistically significant ( F =5.39, P =0.007). Conclusions: Bone mineral density in BPPV group is lower than that in control group. The lower the bone mineral density of the patients, the higher the osteocalcin in BPPV group.

Background: International non-governmental organizations (INGOs) have been implementing community-based tuberculosis (TB) care (CBTBC) in Myanmar since 2011. Although the National TB Programme (NTP) ultimately plans to take over CBTBC, there have been no evaluations of the models of care or of the costs of providing CBTBC in Myanmar by INGOs., Methods: This was a descriptive study using routinely-collected programmatic and financial data from four INGOs during 2013 and 2014, adjusted for inflation. Data analysis was performed from the provider perspective. Costs for sputum examination were not included as it was provided free of charge by NTP. We calculated the average cost per year of each programme and cost per patient completing treatment., Results: Four INGOs assisted the NTP by providing CBTBC in areas where access to TB services was challenging. Each INGO faced different issues in their contexts and responded with a diversity of strategies. The total costs ranged from US$ 140 754 to US$ 550 221 during the study period. The cost per patient completing treatment ranged from US$ 215 to US$ 1 076 for new cases and US$ 354 to US$ 1 215 for retreatment cases, depending on the targeted area and the package of services offered. One INGO appeared less costly, more sustainable and patient oriented than others., Conclusions: This study revealed a wide variety of models of care and associated costs for implementing CBTBC in diverse and challenging populations and contexts in Myanmar. Consequently, we recommend a more comprehensive evaluation, including development of a cost model, to estimate the costs of scaling up CBTBC country-wide, and cost-effectiveness studies, to best inform the NTP as it prepares to takeover CBTBC activities from INGOs. While awaiting evidence from these studies, model of CBTBC that have higher sustainability potential and allocate more resources to patient-centered care should be given priority support.

Cel7A from Rasamsonia emersonii is one of the processive endocellulases classified under family 7 glycoside hydrolase. Molecular dynamics simulations were carried out to obtain the optimized sliding and hydrolyzing conformations, in which the reducing ends of sugar chains are located on different sites. Hydrogen bonds are investigated to clarify the interactions between protein and substrate in either conformation. Nine hydrogen bonding interactions are identified in the sliding conformation, and six similar interactions are also found correspondingly in the hydrolyzing conformation. In addition, four strong hydrophobic interactions are also determined. The domain cross-correlation map analysis shows movement correlation of protein including autocorrelation between residues. The root mean square fluctuations analysis represents the various flexibilities of different fragment in the two conformations. Comparing the two conformations reveals the water-supply mechanism of selective hydrolysis of cellulose in Cel7A. The mechanism can be described as follow. When the reducing end of substrate slides from the unhydrolyzing site (sliding conformation) to the hydrolyzing site (hydrolyzing conformation), His225 is pushed down and rotated, the rotation leads to the movement of Glu209 with the interstrand hydrogen bonding in β-sheet. It further makes Asp211 close to the hydrolysis center and provides a water molecule bounding on its carboxyl in the previous unhydrolyzing site. After the hydrolysis takes place and the product is excluded from the enzyme, the Asp211 comes back to its initial position. In summary, Asp211 acts as an elevator to transport outer water molecules into the hydrolysis site for every other glycosidic bond., (© 2016 Wiley Periodicals, Inc.)

A total of eight Ensifer sp. strains were isolated from two pristine cave environments. One strain was isolated from a cave water pool located in the Wind Cave National Park, South Dakota, USA and the remaining seven strains were isolated from Lechuguilla Cave of Carlsbad Caverns National Park, New Mexico, USA. Whole genome sequencing and comparative genomic analyses of the eight isolates compared to various type strains from the genera Ensifer and Sinorhizobium demonstrates that although members in these genera can be phylogenetically separated into two distinct clades, the percentage of conserved proteins (POCP) between various type strains from Ensifer and Sinorhizobium are consistently higher than 50%, providing strong genomic evidence to support the classification of the genera Ensifer and Sinorhizobium into a single genus., Competing Interests: The authors have declared that no competing interest exists.

Objectives: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal subtype of renal cell carcinoma, whose most effective measure of curing remains diagnosis and nephrectomy in its early phase. However, there is no feasible and recognized plasma biomarker for the clinical diagnosis of ccRCC. The objective of this study is to identify a novel plasma microRNA (miRNA) acting as an efficient diagnostic plasma biomarker in ccRCC., Methods and Materials: The plasma miRNA expression profile was quantified by miRNA microarray. Validation of miRNA levels of plasmas and tissues were performed by quantitative reverse transcription polymerase chain reaction in 106 ccRCC, 28 renal angiomyolipomas (AML), and 123 healthy control plasmas and in 110 ccRCC tissues., Results: We found that plasma miR-144-3p levels in 106 ccRCC plasmas were remarkably up-regulated compared with that in healthy individuals and in patients with AML. miR-144-3p served as a promising plasma biomarker for yielding an area under the receiver operating characteristic curve of 0.91 with 87.10% sensitivity and 83.02% specificity in discriminating ccRCC from healthy individuals, and an area under the curve of 0.82 with 75.00% sensitivity and 71.70% specificity in discriminating ccRCC from patients with AML. In addition, plasma miR-144-3p levels were significantly decreased after surgery in 106 patients with ccRCC. Next, we examined miR-144-3p levels in 110 human ccRCC tissues, and found that miR-144-3p levels in ccRCC tissues were increased compared with adjacent normal tissues. Pearson correlation analysis revealed that miR-144-3p levels in tumor tissues were positively correlated with preoperative plasma miR-144-3p levels in the matched samples from patients with ccRCC. In addition, the miR-144-3p levels in ccRCC plasmas and tissues were increased in patients with advanced pT stage., Conclusions: Our data indicate that miR-144-3p, which is significantly up-regulated in ccRCC plasmas and tissues, particularly with advanced pT stage, is a novel and excellent plasma biomarker for the diagnosis of ccRCC., (Copyright © 2017. Published by Elsevier Inc.)

Dipyridamole (DIP) inhibits thrombus formation when given chronically, and causes vasodilation over a short time. To date, DIP can increase the anticancer drugs (5-fluorouracil, methotrexate, piperidine, vincristine) concentration in cancer cells and hence enhance the efficacy of treatment cancer. The inhibition of DIP may result in increased 5-fluorouracil efficacy and diminish the drug side effects. But the actual molecular targets remain unknown. In this study, reverse protein-ligands docking, and quantum mechanics were used to search for the potential molecular targets of DIP. The quantum mechanics calculation was performed by using Gaussian 03 program package. Reverse pharmacophore mapping was used to search for potential molecular target candidates for a given small molecule. The docking study was used for exploring the potential anti-cancer targets of dipyridamole. The two predicted binders with the statistically significant prediction are dihydropyrimidine dehydrogenase (DPD) (PDB Id: 1GTE) and human spindle checkpoint kinase Bub1 (PDB Id: 3E7E). Structure analysis suggests that electrostatic interaction and hydrogen bonding play an important role in their binding process. The strong functional linkage of DIP and 5FU supports our prediction. In conclusion, these results generate a tractable set of anticancer proteins. The exploration of polypharmacology will provide us new opportunities in treating systematic diseases, such as the cancers. The results would generate a tractable set of anticancer target proteins for future experimental validations.

Background: The co-circulation of 4 DENV serotypes in geographically expanding area, has resulted in increasing occurrence of DENV co-infections. However, studies assessing the clinical impact of DENV co-infections have been scarce and have involved small number of patients. This study explores the impact of DENV co-infection on clinical manifestations and laboratory parameters., Methods: This retrospective study involved consecutive hospitalized patients with non-structural protein 1 (NS1) antigen positivity during an outbreak (Jan to April 2014). Multiplex RT-PCR was performed directly on NS1 positive serum samples to detect and determine the DENV serotypes. All PCR-positive serum samples were inoculated onto C6/36 cells. Multiplex PCR was repeated on the supernatant of the first blind passage of the serum-infected cells. Random samples of supernatant from the first passage of C6/36 infected cells were subjected to whole genome sequencing. Clinical and laboratory variables were compared between patients with and without DENV co-infections., Results: Of the 290 NS1 positive serum samples, 280 were PCR positive for DENV. Medical notes of 262 patients were available for analysis. All 4 DENV serotypes were identified. Of the 262 patients, forty patients (15.3 %) had DENV co-infections: DENV-1/DENV-2(85 %), DENV-1/DENV-3 (12.5 %) and DENV-2/DENV-3 (2.5 %). Another 222 patients (84.7 %) were infected with single DENV serotype (mono-infection), with DENV- 1 (76.6 %) and DENV- 2 (19.8 %) predominating. Secondary dengue infections occurred in 31.3 % patients. Whole genome sequences of random samples representing DENV-1 and DENV-2 showed heterogeneity amongst the DENVs. Multivariate analysis revealed that pleural effusion and the presence of warning signs were significantly higher in the co-infected group, both in the overall and subgroup analysis. Diarrhoea was negatively associated with co-infection. Additionally, DENV-2 co-infected patients had higher frequency of patients with severe thrombocytopenia (platelet count < 50,000/mm(3)), whereas DENV-2 mono-infections presented more commonly with myalgia. Elevated creatinine levels were more frequent amongst the co-infected patients in univariate analysis. Haemoconcentration and haemorrhagic manifestations were not higher amongst the co-infected patients. Serotypes associated with severe dengue were: DENV-1 (n = 9), DENV-2 (n = 1), DENV-3 (n = 1) in mono-infected patients and DENV-1/DENV-2 (n = 5) and DENV-1/DENV-3 (n = 1) amongst the co-infected patients., Conclusion: DENV co-infections are not uncommon in a hyperendemic region and co-infected patients are skewed towards more severe clinical manifestations compared to mono-infected patients.

Objective: To evaluate the diagnosis, management and nasal endoscopic surgical outcome of nasopharyngeal granulomatous mass in post-radiation nasopharyngeal carcinoma (NPC) patients., Materials and Methods: A total of 23 cases of granulomatous mass after radiotherapy for NPC from 2008 to 2013 treated with nasal endoscopic surgery were retrospectively reviewed., Results: Radiotherapy dose (p=0.036) and chemotherapy (p<0.001) correlated with the latency period after the treatment against NPC. The symptoms of the 23 patients before the treatment were nonspecific including nasal obstruction, purulent discharge, headache, epistaxis, foreign body sensation and/or hearing impairment. 12 patients (52.2%) were misdiagnosed to be recurrence of NPC by imaging examination (CT/MRI). After the endoscopic surgery treatment, 18 patients were disease free while the other 5 patients had developed a recurrence. Four of those five recurrent patients were cured with the repeated treatment. Histologic findings of granulation tissue with fibrin and inflammatory cells were found in all of the patients., Conclusions: In situ granulomatous masses in post-radiation NPC patients are very prone to be misdiagnosed as recurrence of nasopharyngeal carcinoma. Chemotherapy is a significant independent factor affecting latency period (p=0.029). The nasal endoscopic surgery is an effective therapy for post-radiation nasopharyngeal granuloma; surgery can not only alleviate symptoms, what is more important, but it also helps to confirm the diagnosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Spatial variability of soil organic matter and its distribution pattern are the hot issues of soil scientific research. Selecting Haigouhe watershed as the study area, this paper mainly focused on the spatial variability, distribution pattern and its impact factors of SOM in the surface soil by classical statistics, Geo-statistics and "3S" technology. The results showed that: compared with the other black soil areas, the SOM content in Haigouhe watershed was a little lower, there was a spatial autocorrelation, and a moderate variability. Random factors, such as human activities, cultivation measures and so on, had little impact on the spatial variation, while the structural factors had a dominant function, and there was a remarkable spatial anisotropy of SOM. The SOM content reduced gradually from east to west with the familiar changes of height, so the co-kriging interpolation, selecting elevation as the co-variate, was employed to improve the accuracy. The spatial variability of SOM and its distribution pattern in Haigouhe watershed were greatly affected by topography and land use but weakly influenced by traffic, villages and other social factors. The surrounding environment of the samples would increase the uncertainty of spatial variability and interpolation of SOM and it cannot be ignored in future studies. In summary, it was a significant scientific research to analyze the spatial variability, distribution pattern of SOM and its main impact factors in a mollisol hilly watershed of China.

The vulnerability and influence factors of agro-household livelihood in Haiyuan County, Ningxia were empirically analyzed utilizing set pair analysis and obstacle degree model, based on field survey data of impoverished agro-households in 2014. Results showed that vulnerability of agro-household livelihood in Haiyuan County was high in general while it exhibited geomorphological and ethnical differences. Vulnerability of agro-households livelihood in plain areas, valleys and intermountain depression areas were lower than that in earth-rock areas, loess ridge areas and moderately high mountain landform areas. Moreover, vulnerability of agro-household livelihood was higher in mixed Hui and Han ethnic villages than in mono Hui or Han ethnic villages. The villagers' lacking of necessities and the stress of sensitive external geographical environment were considered to be the fundamental reasons of vulnerability of agro-household livelihood. The unreasonable livelihood structure and the unvariant livelihood strategy caused the long-term accumulation of livelihood vulnerabi-lity. The nature of the local environment, which was not easy to change, decreased the accessibility of poverty alleviation resources. Building a clear village water rights allocation system, the implementation of counterpart-assistance to educate impoverished families, increasing investment in improving the diversities of means of living, developing the chains of comprehensive commodity market among villages, were necessary to improve the response capability of agro-household livelihood. The management of vulnerability of agro-household livelihood should put the 'Extending Roads to Every Village Project' on a more prominent position in the 'Extending Radio and TV Broadcasting Coverage to Every Village Project'. Furthermore, the combination of meteorological disaster prevention and insurance enterprise disaster reduction should be sought, and the agricultural production insurance system should be developed.

We report here the first high-quality draft genome sequence of Pasteurella multocida sequence type 128, which was isolated from the infected finger bone of an adult female who was bitten by a domestic dog. The draft genome will be a valuable addition to the scarce genomic resources available for P. multocida., (Copyright © 2016 Kavousi et al.)

Patients with dengue fever and comorbidities seem to be at higher risk of developing complications and/or severe dengue compared to healthier individuals. This study systematically reviews the evidence related to comorbidities and dengue. A systematic literature review was performed in five databases (EMBASE, PUBMED, Global Health, SciELO, Cochrane) and grey literature for full-text articles since its inceptions until October 10, 2015. A total of 230 articles were retrieved. Sixteen studies were analysed after applying all inclusion and exclusion criteria. Seven case control studies and nine retrospective cohort studies showed that comorbidities may contribute to severe dengue, especially 1) cardiovascular disease, 2) stroke, 3) diabetes, 4) respiratory disease and 5) renal disease, as well as old age. However, due to heterogeneity in studies, the real estimate effect of comorbidities as modifiers of dengue severity could not be established. Further research in regions with high prevalence of dengue infection would contribute to a better understanding of the relevance of comorbidities in severe dengue, especially with a standardised protocol, for outcomes, specific comorbidities, study design-best using prospective designs-and sample sizes.

Angiotensin-converting enzyme (ACE), a membrane-bound zinc metallopeptidase, catalyzes the formation of Angiotensin-II (AngII) and the deactivation of bradykinin in the renin-angiotensin-aldosterone and kallikrein-kinin systems. As a hydrolysis product of ACE, AngII is regarded as an inhibitor and displays stronger competitive inhibition in the C-domain than the N-domain of ACE. However, the AngII binding differences between the two domains and the mechanisms behind AngII dissociation from the C-domain are rarely explored. In this work, molecular docking, Molecular Mechanics/Poisson-Boltzmann Surface Area calculation, and steered molecular dynamics (SMD) are applied to explore the structures and interactions in the binding or unbinding of AngII with the two domains of human somatic ACE. Calculated free energy values suggest that the C-domain-AngII complex is more stable than the N-domain-AngII complex, consistent with available experimental data. SMD simulation results imply that electrostatic interaction is dominant in the dissociation of AngII from the C-domain. Moreover, Gln106, Asp121, Glu123, and Tyr213 may be the key residues in the unbinding pathway of AngII. The simulation results in our work provide insights into the interactions between the two domains of ACE and its natural peptide inhibitor AngII at a molecular level. Moreover, the results provide theoretical clues for the design of new inhibitors.

To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by A[Formula: see text] via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble A[Formula: see text] (5 [Formula: see text]M) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP[Formula: see text]/DAPI and Tubulin[Formula: see text]/DAPI. Western blotting and real-time PCR analyses were used to observe the effects of OA on NSCs differentiation by examining key targets of the JAK/STAT signal transduction pathway. Compared with normal NSCs, A[Formula: see text]-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the A[Formula: see text]-induced activation of JAK/STAT signaling, with a significant increase in Ngn1 expression and a significant decrease in p-STAT3/STAT3. These results indicate that OA could inhibit the excessive differentiation of NSCs into astrocytes by down-regulating JAK/STAT signaling which might retard the progress of AD.

An assay method for phthalate esters with a complex mixture of isomer of varying carbon numbers, such as di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP), using gas chromatography-mass spectrometry (GC-MS) positive chemical ionization (PCI) with 5% ammonia in methane is described. GC-MS-PCI-NH3, unlike GC-MS electron ionization (EI) (GC-MS-EI) that produces generally m/z 149 ion as the main base peak and low intensity M(+) peaks, produces higher intensity (M + 1) ions that allow the determination of total (R + R') carbon number distributions based on the various R and R' alkyl groups of the di-esters moiety. The technique allows distinguishing among the various commercial DINP and DIDP plasticizers. The carbon number distributions are determined in the acceptable range of <0.1 mole percent to >85 mole percent (m/m). Several examples of analysis made on commercial DINP and DIDP are presented. The use of only 5% instead of 100% ammonia simplifies use of GC-MS-PCI-NH3 but still produces sufficient M + 1 ion intensities that are appropriate for the assay. In addition, use of low concentrations of ammonia mitigates potential safety aspects related to use of ammonia and provides less corrosion for the instrument hardware., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The application of the organophosphate larvicide temephos to water storage containers is one of the most commonly employed dengue vector control methods. This systematic literature review is to the knowledge of the authors the first that aims to assess the community-effectiveness of temephos in controlling both vectors and dengue transmission when delivered either as a single intervention or in combination with other interventions. A comprehensive literature search of 6 databases was performed (PubMed, WHOLIS, GIFT, CDSR, EMBASE, Wiley), grey literature and cross references were also screened for relevant studies. Data were extracted and methodological quality of the studies was assessed independently by two reviewers. 27 studies were included in this systematic review (11 single intervention studies and 16 combined intervention studies). All 11 single intervention studies showed consistently that using temephos led to a reduction in entomological indices. Although 11 of the 16 combined intervention studies showed that temephos application together with other chemical vector control methods also reduced entomological indices, this was either not sustained over time or-as in the five remaining studies--failed to reduce the immature stages. The community-effectiveness of temephos was found to be dependent on factors such as quality of delivery, water turnover rate, type of water, and environmental factors such as organic debris, temperature and exposure to sunlight. Timing of temephos deployment and its need for reapplication, along with behavioural factors such as the reluctance of its application to drinking water, and operational aspects such as cost, supplies, time and labour were further limitations identified in this review. In conclusion, when applied as a single intervention, temephos was found to be effective at suppressing entomological indices, however, the same effect has not been observed when temephos was applied in combination with other interventions. There is no evidence to suggest that temephos use is associated with reductions in dengue transmission.

Objective: To evaluate the efficacy and community effectiveness of larvivorous fish for the control of dengue vectors and dengue transmission, when used as a single agent or in combination with other vector control methods., Method: Comprehensive literature search of published and grey literature using PubMed, EMBASE (DMDI), Web of Science, WHOLIS, WILEY, LILACS, GIFT, Cochrane Library, ELDIS, New York Academy of Medicine Grey Literature Report and Google. All results were checked for duplicates and examined for eligibility. Methodological quality of the studies was assessed using RoBANS., Results: Thirteen articles were considered eligible for inclusion. Incorporating a wide range of interventions and outcome measures, three were efficacy studies and 10 assessed community effectiveness. None of the studies were randomised or cluster-randomised controlled trials. All three efficacy studies and seven community effectiveness studies investigated fish as a single agent. All efficacy studies reported elimination of Aedes larvae from treated containers, while community effectiveness studies reported reductions in immature vector stages, two of which also detected a continuous decline over 2 years. An impact on adult mosquitoes was shown in only two community effectiveness studies. Reductions in dengue cases following intervention were reported in two studies, but it was not possible to attribute this to the intervention., Conclusion: While the use of larvivorous fish as a single agent or in combination with other control measures could lead to reductions in immature vector stages, considerable limitations in all the studies restricted any conclusions with respect to the evaluation of community effectiveness. Evidence for the community effectiveness of larvivorous fish as a single agent remains minimal and cluster-randomised controlled studies that include the assessment of impact on dengue are recommended., (© 2015 John Wiley & Sons Ltd.)