Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced severe hypoglycemia with insulin glargine in intensively treated adults with type 1 diabetes.

BACKGROUND The goal of new therapies introduced for type 1 diabetes should be to decrease hypoglycemic episodes while improving glycemic control. METHODS A database was used to computer match the baseline A1C values in 196 subjects with type 1 diabetes receiving multiple daily injections (MDI) consisting of four or more injections per day. There were 98 patients transferred from NPH to insulin glargine (Lantus, Aventis Pharmaceuticals, Bridgewater, NJ), and 98 patients remained on NPH throughout the study. The gender distribution and mean age (approximately 32 years), duration of diabetes (approximately 16 years), and duration of treatment (approximately 13 months) were not significantly different between the groups. The majority of patients were well controlled (>50% in both groups had an A1C <7%). RESULTS The mean A1c values were not significantly different in the groups at baseline or at follow-up. Severe hypoglycemic episodes per patient per year were significantly lower in the glargine group compared with the NPH group (0.5 vs. 1.2, respectively; P = 0.04). The mean end-of-study total (P = 0.03) and long-acting (P = 0.0001) doses were significantly reduced from baseline in the group that switched to glargine, but not in the group that remained on NPH, with no change in the short-acting dose in either group. The weight gain was significantly higher in the NPH group at the end of the study (P = 0.004) with no significant change in the glargine group. CONCLUSIONS Transfer to glargine treatment from NPH in MDI regimens significantly reduces severe hypoglycemic episodes despite a decline in long-acting basal insulin without significant weight gain.
Shuyu capsules relieve liver-qi depression by regulating ERK-CREB-BDNF signal pathway in central nervous system of rat

The purpose of this study was to investigate the possible therapeutic mechanism of Shuyu capsules in liver-qi depression. Liver-qi depression rats were prepared based on chronic unpredictable mild stress (CUMS) and delayed constraint. Rats were gavaged with Shuyu capsule, fluoxetine, Radix Bupleuri and Radix Paeoniae Alba to constrct rat models. Body weight test, sucrose preference test and open-field test were applied to test rat models. Western blot analysis and quantitative real-time PCR was applied to determine the relative expression of extracellular signal-regulated protein kinase (ERK), cyclic AMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in hippocampus and frontal lobe tissues. ELISA was used to detect the content of BDNF in serum. Body weight, sugar intake and total distance were significantly decreased in depression group compared with control. The four drugs significantly increased levels of these factors. Compared with control group, ERK, CREB and BDNF expression were significantly decreased in depression group in both hippocampus and frontal lobe tissues at both mRNA and protein level. Shuyu capsule and fluoxetine group showed a significant increase in the expression of ERK, CREB and BDNF at mRNA, p-ERK and p-BDNF at protein level. Compared with Radix Paeoniae Alba, Radix Bupleuri were better in the rescue of ERK, CREB and BDNF expression. In conclusion, the pathogenesis of liver-qi depression associated with lower expression of ERK, CREB and BDNF in hippocampus and frontal. Shuyu capsule and main constitution alleviated the depressive-like behaviors and reversed the disruptions of the p-ERK, p-CREB and BDNF in stressed rats.
Efficacy and safety of perioperative appliance of sunitinib in patients with metastatic or advanced renal cell carcinoma

Background: The aim of this systematic review and meta-analysis is to comprehensively evaluate the efficacy and safety of the perioperative use of sunitinib in patients with metastatic and advanced renal cell carcinoma (RCC). Materials and methods: We searched authenticated databases for related clinical studies. The baseline characteristics, parameters concerning the efficacy and safety of the perioperative use of sunitinib were extracted for subsequent comprehensive analysis. The parameters which reflected the efficacy and safety as overall survival (OS), progression-free survival (PFS), occurrence rate of all-grade and grade ≥3 adverse effects (AEs) were carefully pooled using comprehensive meta-analysis. Results: We finally recruited 411 patients from 14 eligible studies. We found proteinuria (75.0%, 95% CI 62.1%–84.6%), anemia (71.6%, 95% CI 60.9%–80.3%), athesia (60.0%, 95% CI 40.3%–77.0%), pause symptoms (59.2%, 95% CI 49.2%–68.4%), arterial hypertension (53.1%, 95% CI 43.2%–62.7%), and thrombocytopenia (52.5%, 95% CI 44.8%–60.0%) to be the most common all-grade AEs. And arterial hypertension, athesia, cutaneous toxicity, hypophosphatemia, leukopenia, pain, pause syndrome, renal dysfunction, and thrombocytopenia were the most common types of grade ≥3 AEs. In addition, objective response rate (ORR) of sunitinib to both the original and metastatic tumor sites increased with the use of sunitinib, so did the OS and PFS. Conclusion: Common all-grade and grade ≥3 AEs were carefully monitored. The perioperative use of sunitinib showed superior ORR, OS, and PFS rates. Nevertheless, more studies are required to further verify these findings.
Redrawing medical professional domains: new doctors, shifting boundaries, and traditional force fields.

PURPOSE This paper aims to investigate the forces that influence the shifting of professional boundaries on the entry of a new medical occupation in Dutch hospitals - non-specialist emergency physicians. DESIGN/METHODOLOGY/APPROACH Five case studies of Dutch hospitals were conducted and the emergency physicians' implementation process was analyzed by means of force field analysis. FINDINGS Emergency physicians were conceptualized as being the answer to unequivocal contextual changes. However, their contribution to better performance varies due to problems in the implementation process. Strong socio-political forces between traditional specialties and these new doctors mediate the intended improvement. The emergency physicians aim to establish their own organizational-, patient- and knowledge-domain by redrawing professional boundaries but they are not on a par with the specialists who set these boundaries. Consequently, emergency physicians only gradually redraw the existing boundaries, resulting in limited added value. Their reaction is to obtain power by striving to develop into a recognized specialty; ironically, by becoming an additional layer in the traditional medical hierarchy they might lose their envisaged added value. RESEARCH LIMITATIONS/IMPLICATIONS This paper is based on the first Dutch hospitals that implemented emergency physicians. The number of cases is therefore limited. Moreover, the study took place at an early stage of emergency physician implementation. PRACTICAL IMPLICATIONS The extent of successful redrawing depends on the implementation's transition logic, the existing degree of differentiation and boundary permeability and on the ideological power developed by the leaders. ORIGINALITY/VALUE The introduction of emergency physicians is currently being discussed in many countries worldwide, and some countries consider following the Dutch example of non-specialist doctors. This paper supports health professionals and hospital managers in not falling prey to the same pitfalls as some Dutch hospitals.
Effects of TNF-α blocking on experimental periodontitis and type 2 diabetes in obese diabetic Zucker rats.

OBJECTIVE Tumour necrosis factor α (TNF-α) is considered a key signalling modulator in the pathogenesis of both periodontitis (PD) and type 2 diabetes mellitus (DM2). This study aims at elucidating the effect of TNF-α blocking on the interplay between PD and DM2. METHODS Obese diabetic Zucker rats and their lean littermates were divided into five treatment groups with or without periodontitis. Anti-TNF-α treatment was provided with Etanercept injections. Diabetic state was evaluated by oral glucose tolerance test, the homeostatic model assessment, free fatty acids and blood glucose. Systemic inflammation was assessed by measurement of interleukin (IL)-1β, IL-6 and TNF-α in plasma. Kidney complications were evaluated by real-time rtPCR, creatinine clearance rate, urinary albumin excretion and increase in weight. PD was evaluated by registration of alveolar bone level. RESULTS After 4 weeks the diabetic state was modified by Etanercept treatment with lower insulin levels and lower homeostatic model assessment. Furthermore, while kidney complications were reduced by Etanercept treatment, PD had no effect. PD was influenced by diabetic state, but the impact was attenuated by Etanercept treatment. CONCLUSION In this study anti-TNF-α treatment improved glucose tolerance and compensated for the increased periodontal disease in obese diabetic Zucker. PD did not influence diabetic parameters assessed including complications of the rats kidneys.
Calprotectin (a major leucocyte protein) is associated with the levels of anti‐CCP and rheumatoid factor in a longitudinal study of patients with very early rheumatoid arthritis

Background: Calprotectin is a major granulocyte and monocyte protein, and plasma levels of calprotectin are strongly associated with inflammation in patients with rheumatoid arthritis (RA). Objective: To explore the associations between calprotectin and serological, inflammatory, and clinical assessments in a longitudinal study of patients with very early RA. Patients and methods: In 61 RA patients (77% females, mean age 57.9 years, disease duration 132 days), laboratory and clinical assessments were performed at baseline and after 3, 6, and 12 months. Results: Calprotectin levels were higher in patients positive vs. negative for anti‐cyclic citrullinated peptide (anti‐CCP), immunoglobulin M rheumatoid factor (IgM‐RF), and IgA‐RF (p<0.001–0.05). The 1‐year averaged level of calprotectin correlated significantly with the mean levels of these three serological markers (p<0.05). In multiple regression analyses, adjusting for age, sex, and disease duration, calprotectin was associated with anti‐CCP (p = 0.045), and both calprotectin and erythrocyte sedimentation rate (ESR) were associated with IgM‐RF (p = 0.003 and 0.03, respectively). Calprotectin correlated significantly with the inflammatory markers at all examinations [C‐reactive protein (CRP); r = 0.60–0.70, p<0.001, ESR; r = 0.55–0.57, p<0.001] as well as with the 28‐joint disease activity score (DAS28; r = 0.28–0.33, p<0.05). Conclusion: This is the first study that shows significant associations between the levels of calprotectin and anti‐CCP, IgA‐RF, and IgM‐RF in very early RA. In addition, significant correlations were found between calprotectin and markers of disease activity.
Medical Clerkship in a State Registration and Reception Center for Forced Migrants in Germany: Students’ Experiences, Teachable Moments, and Psychological Burden

Aspects of global health are becoming increasingly relevant for doctors of future generations. However, medical curricula rarely include courses which focus on global health or forced migration. Furthermore, it remains unclear whether students are at risk to develop psychological strain, after being confronted with highly burdened or even traumatized asylum seekers. This is a prospective study using a mixed-methods approach. We included n = 22 medical students performing a medical clerkship in a state registration and reception center for refugees. By applying (1) qualitative interviews, (2) reflective diaries, and (3) psychometric questionnaires, we examined the students’ experiences, teachable moments, and potential psychological burdens. In the interviews, the students emphasized the importance of cultural sensitivity during their clerkship. However, they also reported cognitive changes concerning their views of themselves and the world in general; this could indicate vicarious traumatization. The reflective diaries displayed high learning achievements. According to the psychometric questionnaires, the assignment in the reception center had not caused any significant psychological strain for the students. By completing their medical clerkship in a reception center, students were able to improve their medical, organizational, and interactional knowledge and skills. Furthermore, they reported that they had broadened their personal and cultural horizons.
Prevalence and Related Factors of Urinary Incontinence among Hebei Women of China

Background/Aims: The aim of this study was to assess the prevalence and related factors of different types of urinary incontinence (UI) among Hebei women in China. Methods: A total of 2,500 women aged 20 years or more were sampled and interviewed face-to-face by well-trained interviewers. Results: Among these women, 35.2% (862/2,448) had UI. The prevalence of stress, urge, and mixed UI was 26.4% (647/2,448), 1.9% (47/2,448), and 6.9% (168/2,448), respectively. In multivariable logistic regression, age, constipation, pelvic organ prolapse, number of abortions, and cesarean sections were associated with both stress and mixed UI; body mass index, dysmenorrhea, vaginitis and cervicitis, fetal weight, and dystocia were associated with stress UI only; age of menarche and dystocia were associated with urge UI only, and living in a city or countryside, a history of pelvic operation, urinary infection, diseases of the respiratory system, heart disease, and alcohol consumption with mixed UI. Conclusions: UI is a highly prevalent condition among women in Hebei Province, PR China. Stress, urge, and mixed UI not only have some related factors in common but also have some different ones. Economic condition and a lack of UI-related knowledge are factors keeping patients from seeing a doctor.
In developing mouse kidneys, orientation of loop of Henle growth is adaptive and guided by long‐range cues from medullary collecting ducts

The path taken by the loop of Henle, from renal cortex to medulla and back, is critical to the ability of the kidney to concentrate urine and recover water. Unlike most developing tubules, which navigate as blind‐ended cylinders, the loop of Henle extends as a sharply bent loop, the apex of which leads the double tubes behind it in a ‘V’ shape. Here, we show that, in normal kidney development, loops of Henle extend towards the centroid of the kidney with an accuracy that increases the longer they extend. Using cultured kidney rudiments, and manipulations that rotate or remove portions of the organ, we show that loop orientation depends on long‐range cues from the medulla rather than either the orientation of the parent nephron or local cues in the cortex. The loops appear to be attracted to the most mature branch point of the collecting duct system but, if this is removed, they will head towards the most mature collecting duct branch available to them. Our results demonstrate the adaptive nature of guidance of this unusual example of a growing epithelium, and set the stage for later work devoted to understanding the molecules and mechanisms that underlie it.
Current diagnosis and management of erectile dysfunction

Erectile dysfunction (ED) is a common male sexual dysfunction associated with a reduced quality of life for patients and their partners. ED is associated with increasing age, depression, obesity, lack of exercise, diabetes mellitus, hypertension, dyslipidaemia, cardiovascular disease and lower urinary tract symptoms related to benign prostatic hyperplasia. The evaluation of men with ED requires a full medical and personally and culturally sensitive sexual history, a focused clinical examination, fasting glucose levels, a fasting lipid profile and, in select cases, a total testosterone level and a prostate‐specific antigen test. Treatment of ED requires lifestyle modification, reduction of comorbid vascular risk factors, and treatment of organic or psychosexual dysfunction with either pharmacotherapy alone or in combination with psychosexual therapy. Between 60% and 65% of men with ED, including those with hypertension, diabetes mellitus, spinal cord injury and other comorbid medical conditions, can successfully complete intercourse in response to the phosphodiesterase type 5 inhibitors (PDE5i) sildenafil, tadalafil, vardenafil and avanafil. Patient‐administered intracorporal injection therapy using vasodilator drugs such as alprostadil is an effective treatment and is useful in men who fail to respond to oral pharmacological agents. Surgical treatment of ED with multicomponent inflatable penile implants is associated with high satisfaction rates. Penile arterial revascularisation and venous ligation surgery are associated with relatively poor outcome results in men with penile atherosclerotic disease or corporal veno‐occlusive dysfunction.
Determinants of anxiety in elite athletes: a systematic review and meta-analysis

Objective To identify and quantify determinants of anxiety symptoms and disorders experienced by elite athletes. Design Systematic review and meta-analysis. Data sources Five online databases (PubMed, SportDiscus, PsycINFO, Scopus and Cochrane) were searched up to November 2018 to identify eligible citations. Eligibility criteria for selecting studies Articles were included if they were published in English, were quantitative studies and measured a symptom-level anxiety outcome in competing or retired athletes at the professional (including professional youth), Olympic or collegiate/university levels. Results and summary We screened 1163 articles; 61 studies were included in the systematic review and 27 of them were suitable for meta-analysis. Overall risk of bias for included studies was low. Athletes and non-athletes had no differences in anxiety profiles (d=−0.11, p=0.28). Pooled effect sizes, demonstrating moderate effects, were identified for (1) career dissatisfaction (d=0.45; higher anxiety in dissatisfied athletes), (2) gender (d=0.38; higher anxiety in female athletes), (3) age (d=−0.34; higher anxiety for younger athletes) and (4) musculoskeletal injury (d=0.31; higher anxiety for injured athletes). A small pooled effect was found for recent adverse life events (d=0.26)—higher anxiety in athletes who had experienced one or more recent adverse life events. Conclusion Determinants of anxiety in elite populations broadly reflect those experienced by the general population. Clinicians should be aware of these general and athlete-specific determinants of anxiety among elite athletes.
Insight on Propolis from Mediterranean Countries: Chemical Composition, Biological Activities and Application Fields

This review updates the information upon the chemical composition of propolis from all Mediterranean countries as well as their biological properties and applications. The non‐volatile fraction of propolis was characterized by the presence of phenolic acids and their esters and flavonoids. Nevertheless, in some countries, diterpenes were also present: Sicily (Italy), Croatia, Malta, Creta (Greece), Turkey, Cyprus, Egypt, Libya, Algeria and Morocco. The volatile fraction of propolis was characterized by the presence of benzoic acid and its esters, mono‐ and sesquiterpenes, being the oxygenated sesquiterpene β‐eudesmol characteristic of poplar propolis, whereas the hydrocarbon monoterpene α‐pinene has been related with the presence of conifers. Regardless the chemical composition, there are common biological properties attributed to propolis. Owing to these attributes, propolis has been target of study for applications in diverse areas, such as food, medicine and livestock.
Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability

Abstract Objectives. Bipolar II (BPII) depression is commonly misdiagnosed as unipolar depression (UD); however, an objective and reliable tool to differentiate between these disorders is lacking. Whether cardiac autonomic function can be used as a biomarker to distinguish BPII from UD is unknown. Methods. We recruited 116 and 591 physically healthy patients with BPII depression and UD, respectively, and 421 healthy volunteers aged 20–65 years. Interviewer and self-reported measures of depression/anxiety severity were obtained. Cardiac autonomic function was evaluated by heart rate variability (HRV) and frequency-domain indices of HRV. Results. Patients with BPII depression exhibited significantly lower mean R–R intervals, variance (total HRV), low frequency (LF)-HRV, and high frequency (HF)-HRV but higher LF/HF ratio compared to those with UD. The significant differences remained after adjusting for age. Compared to the controls, the patients with BPII depression showed cardiac sympathetic excitation with reciprocal vagal impairment, whereas the UD patients showed only vagal impairment. Depression severity independently contributed to decreased HRV and vagal tone in both the patients with BPII depression and UD, but increased sympathetic tone only in those with BPII depression. Conclusions. HRV may aid in the differential diagnosis of BPII depression and UD as an adjunct to diagnostic interviews.
uNK cell‐derived TGF‐β1 regulates the long noncoding RNA MEG3 to control vascular smooth muscle cell migration and apoptosis in spiral artery remodeling

Successful pregnancy depends on correct spiral artery (SpA) remodeling, and thus, on normal patterns of the vascular smooth muscle cell (VSMC) apoptosis and migration. Uterine natural killer (uNK) cells‐derived transforming growth factor β1 (TGF‐β1) is known to mediate the separation of VSMC layers via as yet unknown mechanisms. Likewise, the long noncoding RNA maternally expressed gene 3 (MEG3) is a tumor suppressor that has been shown to regulate cancer cell apoptosis and migration; however, its role in VSMC loss is unclear. Thus, the aim of the present study was to assess the effects of uNK‐derived TGF‐β1 and MEG3 on VSMC function during SpA. Analyses were conducted to assess the effects of downregulating MEG3 expression, and/or administering treatments to increase or block TGF‐β1 signaling on VSMC survival and behavior. The results of these analyses showed that treating the VSMC with uNK cell‐derived supernatant or recombinant human TGF‐β1 promoted MEG3 and matrix metalloprotease 2 expression and VSMC apoptosis and migration, and suppressed VSMC proliferation. Conversely, MEG3 silencing promoted VSMC proliferation and inhibited VSMC apoptosis and migration. Notably, TGF‐β1 signaling induction had no significant effect on the proliferation, apoptosis, nor migration of the MEG3‐silenced VSMC. Together, these findings suggest that MEG3 is regulated by uNK‐derived TGF‐β1, and itself mediates VSMC apoptosis and migration; thus, it may be an important positive regulator of VSMCs separation during maternal SpA remodeling.