Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of individual and group programmes to treat obesity and reduce cardiovascular disease risk factors in pre‐pubertal children

Childhood obesity results in premature atherosclerosis and requires early intervention. Compare the effectiveness of 6‐month lifestyle interventions (with choice of either individual or group therapy) with standard care on body mass index (BMI) z‐score and cardiovascular disease (CVD) risks factors in children with obesity. This 6‐month randomized controlled trial with a 6‐month follow‐up included 74 pre‐pubertal children with obesity (7.5‐11.9 years) assigned randomly (2:1) to intervention or control. Families in the intervention arm choose between an individually delivered treatment (3 hours paediatrician + 4 hours dietician) or group treatment (35 hours with a multidisciplinary team). Children participated also to a weekly physical activity programme. We measured BMI, BMI z‐score; waist circumference (WC); total and abdominal fat; blood pressure; common carotid artery intima‐media thickness and incremental elastic modulus (Einc); endothelium‐dependent and independent dilation (nitroglycerin‐mediated dilation [NTGMD]) of the brachial artery; fasting plasma glucose, insulin, lipids; and high‐sensitivity C‐reactive protein (hs‐CRP). Compared to controls, at 6 months, abdominal fat and hs‐CRP were reduced in both interventions. The group intervention was also effective in reducing BMI (−0.55 kg/m2; 95% confidence interval −1.16 to 0.06) and BMI z‐score (−0.08; −0.15 to 0.00) at 6 months and BMI, BMI z‐score, WC, NTGMD, total and abdominal fat at 12 months. Abdominal fat and low‐grade inflammation were significantly decreased in both interventions. High‐intensity group treatment improved early signs of atherosclerosis in children with obesity. These findings are important for the promotion of cardiometabolic health in this population.
Potential Confounding Effects of Intensity on Training Response.

We read with great interest the important study by Zinner et al. (1) that suggested a greater risk of nonresponding when recreational runners complete both polarized (POL) and high-intensity (HIGH) training mesocycles, when compared to a low intensity (LOW)mesocycle. Although this study presents several methodological strengths and valuable information,we feel compelled to point out some potential challenges in the interpretation of the results. First, from a coaching perspective, we would argue that the loads completed in all the training programswere very demanding, based on the training background of the novice runners who served as participants. This is not a trivial issue given the high number of evaluations conducted, including eight maximal efforts over 8 wk, which, when added to the training workload (volume–intensity), may well have induced suboptimal adaptations or even overreaching in some cases. For this group of runners, the training plus testing may have been an excessive load increase. In our experience as both researchers and coaches, a lower total workload, independent of intensity distribution, might be expected to induce a better performance outcome in the three experimental groups in this study (1). For instance, a previous study (2) with active nonrunners showed significant improvements in running performance after 4 wk of interval versus continuous training regimes equated by total load, but with an importantly lower training volume when compared to the current study (1). Furthermore, this is especially relevant in the POL and HIGH groups because only these groups were exposed to the highly demanding 4 4 min sessions (3). Therefore, although the minimum dose for optimal adaptations in novice runners remains to be clarified in further studies, we would like to know the authors’ opinion about these issues, considering also that habitual (nontraining) physical activity has been previously demonstrated to influence aerobic adaptations of recreational runners (4). Second, the methods selected for training prescription and monitoring are not without some limitations. For instance, as the training impulse load was increased by 50% during the 3-wk mesocycle, based on the 4-wk wash-in mesocycle, the POL group seems likely to have been exposed to a greater training load than the other groups as they exhibited a significantly greater weekly training impulse during the wash-in mesocycle. Further, the intensity distribution of POL (see Table 1) during the 3-wk mesocycle is not a good reproduction of the typical
Single Centre Experience in Patients with Primary Hyperparathyroidism: Sporadic, Lithium-associated and in Multiple Endocrine Neoplasia

Abstract Purpose It is assumed that primary hyperparathyroidism (pHPT) in Multiple Endocrine Neoplasia (MEN) and lithium-associated pHPT (LIHPT) are associated with multiple gland disease (MGD), persistence and recurrence. The studies purpose was to determine frequencies, clinical presentation and outcome of sporadic pHPT (spHPT), LIHPT and pHPT in MEN. Additional main outcome measures were the rates of MGD and persistence/recurrence. Methods Retrospective analysis of medical records of 682 patients with pHPT who had attended the University Hospital of Marburg between 01–01–2004 and 30–06–2013. All patients were sent a questionnaire asking about their history of lithium medication. Results Out of 682 patients, 557 underwent primary surgery (532 spHPT, 5 LIHPT, 20 MEN), 38 redo-surgery (31 spHPT, 7 MEN), 55 were in follow-up due to previous surgery (16 spHPT, 1 LIHPT, 38 MEN) and 37 were not operated (33 spHPT, 1 LIHPT, 3 MEN). Primary surgeries were successful in 97.4%, revealed singular adenomas in 92.4%, double adenomas in 2.9% and MGD in 3.4% of the cases. Rates of MGD in MEN1 (82.35%) were significantly higher than in spHPT (3.8%), while there was no significant difference between LIHPT (20%) and spHPT. Rates of persistence/recurrence did not significantly differ due to type of surgery (bilateral/unilateral) or type of HPT (spHPT/LIHPT/MEN). Conclusions History of lithium medication is rare among pHPT patients. While MGD is common in MEN1, rates of MGD, persistence or recurrence in LIHPT were not significantly higher than in spHPT.
Behavioral Effects of Opioid Full and Partial Agonists During Chronic Buprenorphine Treatment

Buprenorphine, a partial agonist at the μ-opioid receptor, is commonly prescribed for the management of opioid addiction. Notwithstanding buprenorphine’s clinical popularity, the relationship between its effectiveness in attenuating relapse-related behavior and its opioid efficacy is poorly understood. Furthermore, changes in the antinociceptive potency or effectiveness of opioid drugs that might occur during buprenorphine treatment have not been characterized. Here, we address these questions by assessing the ability of daily buprenorphine treatment to protect against the reinstatement of drug-seeking behavior by six opioids differing in efficacy (methadone, heroin, oxycodone, buprenorphine, butorphanol, nalbuphine) and, in separate experiments, by determining how such treatment may modify their antinociceptive effects. In one set of experiments, squirrel monkeys were trained to respond under concurrent schedules (choice) of food or intravenous oxycodone presentations. The priming strength of different opioids during sessions in which saline, rather than oxycodone, was available for intravenous self-administration was determined before and during chronic buprenorphine treatment (0.1 or 0.32 mg/kg per day). In other subjects, antinociceptive effects of the different opioids were assessed using cumulative dosing procedures in a modified warm-water tail withdrawal procedure before and during buprenorphine treatment. Results show that, notwithstanding some tolerance, full agonists retain high efficacy in producing priming and antinociceptive effects. In contrast, both the priming strength and antinociceptive effectiveness of partial agonists were decreased. These results suggest that the utility of buprenorphine in the management of opioid addiction, and how it alters the analgesic effects of opioids, can vary depending on the efficacy of the abused or prescribed opioid. SIGNIFICANCE STATEMENT Our findings indicate that the pharmacological efficacy of abused opioids may predict the ability of buprenorphine to attenuate their relapse-related priming and analgesia-related antinociceptive effects. This information can help inform physicians as to the effectiveness and limitations of buprenorphine as a pharmacotherapy for opioid addiction.
Oxidative stress and inflammation in the evolution of heart failure: From pathophysiology to therapeutic strategies

Both oxidative stress and inflammation are enhanced in chronic heart failure. Dysfunction of cardiac mitochondria is a hallmark of heart failure and a leading cause of oxidative stress, which in turn exerts detrimental effects on cellular components, including mitochondria themselves, thus generating a vicious circle. Oxidative stress also causes myocardial tissue damage and inflammation, contributing to heart failure progression. Furthermore, a subclinical inflammatory state may be caused by heart failure comorbidities such as obesity, diabetes mellitus or sleep apnoeas. Some markers of both oxidative stress and inflammation are enhanced in chronic heart failure and hold prognostic significance. For all these reasons, antioxidants or anti-inflammatory drugs may represent interesting additional therapies for subjects either at high risk or with established heart failure. Nonetheless, only a few clinical trials on antioxidants have been carried out so far, with several disappointing results except for vitamin C, elamipretide and coenzyme Q10. With regard to anti-inflammatory drugs, only preliminary data on the interleukin-1 antagonist anakinra are currently available. Therefore, a comprehensive, deep understanding of our current knowledge on oxidative stress and inflammation in chronic heart failure is key to providing some suggestions for future research on this topic.
Regional Variability in Longitudinal Strain Across Vendors in Patients With Cardiomyopathy Due to Increased Left Ventricular Wall Thickness.

BACKGROUND Cardiomyopathies with increased left ventricular wall thickness such as cardiac amyloidosis, septal hypertrophic cardiomyopathy (HCM), and apical HCM exhibit characteristic regional longitudinal strain (LS) patterns. However, between-vendor agreement of segmental and regional LS has not been tested in these diseases. We sought to assess LS values among vendors in specific cardiomyopathies that exhibit regional strain variation: cardiac amyloidosis, septal HCM, and apical HCM. METHODS This was a prospective, cross-sectional study of 69 patients (18 amyloidosis, 30 septal HCM, 6 apical HCM, and 15 controls) who underwent clinically indicated outpatient echocardiography at the Cleveland Clinic. Peak systolic segmental, regional (basal, mid, and apical), and global LS were evaluated using GE (EchoPAC), Siemens (Velocity Vector Imaging), and Phillips (QLab) systems in the same imaging session. Between-vendor, differences were analyzed using correlation coefficients, Bland Altman plots, and a mixed model. RESULTS Global LS was highly correlated among the 3 software packages and most abnormal in patients with amyloidosis (P<0.001). Regional LS analysis demonstrated that QLab software tended to produce more negative LS values, driven by differences in apical strains. EchoPAC had the greatest ability to discriminate patients with amyloidosis using regional strain values (area under the curve, 0.932) as compared with Velocity Vector Imaging and QLab (P<0.001). CONCLUSIONS Global and regional variations in LS exist between-vendors in patients with cardiomyopathies with increased left ventricular wall thickness (amyloidosis, septal HCM, and apical HCM). It is important to be aware of these differences for diagnosis, prognosis, and serial examinations in these conditions.
Evaluating strategies to improve rotavirus vaccine impact during the second year of life in Malawi

Administering an additional dose of rotavirus vaccine at 9 months of age in Malawi is predicted to lead to only modest improvements in vaccine impact. Examining disparity in protection against rotavirus The rotavirus vaccine is less effective in low-income countries compared to high-income countries, although the reasons for this are unknown. Pitzer et al. used mathematical modeling to analyze infection data in Malawian children before and after the introduction of a rotavirus vaccine to examine the nature of vaccine-induced immunity. They found that endemic infection increased the protection observed in the clinical study control arm, reducing the apparent efficacy of the vaccine arm. The authors also determined that a booster dose at 9 months is unlikely to lead to substantially improved protection and suggest that efforts may be better placed into developing a more immunogenic vaccine. Rotavirus vaccination has substantially reduced the incidence of rotavirus-associated gastroenteritis (RVGE) in high-income countries, but vaccine impact and estimated effectiveness are lower in low-income countries for reasons that are poorly understood. We used mathematical modeling to quantify rotavirus vaccine impact and investigate reduced vaccine effectiveness, particularly during the second year of life, in Malawi, where vaccination was introduced in October 2012 with doses at 6 and 10 weeks. We fitted models to 12 years of prevaccination data and validated the models against postvaccination data to evaluate the magnitude and duration of vaccine protection. The observed rollout of vaccination in Malawi was predicted to lead to a 26 to 77% decrease in the overall incidence of moderate-to-severe RVGE in 2016, depending on assumptions about waning of vaccine-induced immunity and heterogeneity in vaccine response. Vaccine effectiveness estimates were predicted to be higher among 4- to 11-month-olds than 12- to 23-month-olds, even when vaccine-induced immunity did not wane, due to differences in the rate at which vaccinated and unvaccinated individuals acquire immunity from natural infection. We found that vaccine effectiveness during the first and second years of life could potentially be improved by increasing the proportion of infants who respond to vaccination or by lowering the rotavirus transmission rate. An additional dose of rotavirus vaccine at 9 months of age was predicted to lead to higher estimated vaccine effectiveness but to only modest (5 to 16%) reductions in RVGE incidence over the first 3 years after introduction, regardless of assumptions about waning of vaccine-induced immunity.
Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study

Abstract Background First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. Methods We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS. Results In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group. Conclusions The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Impacting Health through Cross-Border Pharmaceutical Purchases

ABSTRACT Annually, retirees known as Winter Texans travel to spend the winter along the Texas/Mexico border and while there, many purchase medicine in Mexico. However, strategies that are used when purchasing Mexican medicine and the health implications of doing so have not been adequately explored. The results of the study we report illustrate that Winter Texans are knowledgeable about their healthcare and act more as choice-making consumers than patients seeking care. Furthermore, the use of Mexican medication did not increase rates of adverse drug events or decrease health-related quality of life scores. Video abstract Read the transcript Watch the video on Vimeo
Guidelines for the Management of Retinal Vein Occlusion by the European Society of Retina Specialists (EURETINA)

The high prevalence of cardiovascular disease particularly in the elderly population is associated with retinal vascular disease. Retinal vein occlusions represent severe disturbances of the hypoxia-sensitive neurosensory retina. Acute and excessive leakage leads to the diagnostic hallmarks of retinal hemorrhage and edema with substantial retinal thickening. Advanced diagnostic tools such as OCT angiography allow to evaluate retinal ischemia and identify the risk for late complications and will soon reach clinical routine besides fluorescein angiography. Accordingly, the duration of non-perfusion is a crucial prognostic factor requiring timely therapeutic intervention. With immediate inhibition of vascular leakage, anti-VEGF substances excel as treatment of choice. Multiple clinical trials with optimal potential for functional benefit or a lesser regenerative spectrum have evaluated aflibercept, ranibizumab, and bevacizumab. As retinal vein occlusion is a chronic disease, long-term monitoring should be individualized to combine maintenance with practicability. While steroids may be considered in patients with systemic cardiovascular risk, surgery remains advisable only for very few patients. Destructive laser treatment is an option if reliable monitoring is not feasible. Ophthalmologists are also advised to perform a basic systemic workup to recognize systemic concomitants. The current edition of the EURETINA guidelines highlights the state-of-the-art recommendations based on the literature and expert opinions in retinal vein occlusion.
Not Just Going with the Flow: The Effects of Fluid Flow on Bacteria and Plankton.

Microorganisms often live in habitats characterized by fluid flow, from lakes and oceans to soil and the human body. Bacteria and plankton experience a broad range of flows, from the chaotic motion characteristic of turbulence to smooth flows at boundaries and in confined environments. Flow creates forces and torques that affect the movement, behavior, and spatial distribution of microorganisms and shapes the chemical landscape on which they rely for nutrient acquisition and communication. Methodological advances and closer interactions between physicists and biologists have begun to reveal the importance of flow-microorganism interactions and the adaptations of microorganisms to flow. Here we review selected examples of such interactions from bacteria, phytoplankton, larvae, and zooplankton. We hope that this article will serve as a blueprint for a more in-depth consideration of the effects of flow in the biology of microorganisms and that this discussion will stimulate further multidisciplinary effort in understanding this important component of microorganism habitats. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 35 is October 7, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Retinal Pigment Epithelial Cell Line with Fast Differentiation and Improved Barrier Properties

Retinal pigment epithelium (RPE) acts as an outer blood–retinal barrier that limits the access of circulating xenobiotics to the eye. In addition, the RPE limits posterior elimination of intravitreally injected drugs to circulation. Thus, permeation in the RPE has a significant effect on ocular pharmacokinetics. The RPE is also a potentially important drug target in age-related macular degeneration. Therefore, the cell models of the RPE are important tools in ocular drug development, but poor availability and problems in reproducibility limit the use of primary RPE cell cultures. Furthermore, the best and widely used human cell line ARPE19 requires specialized culture conditions and a long time for cellular differentiation. In this paper, we describe a cell population arisen from the ARPE19 culture, with fast differentiation and improved barrier properties. This cell line, LEPI, forms clear microvilli and rapidly displays RPE-like cobblestone morphology after subculture in simple culture conditions. The LEPI cells show RPE-specific functions and expression of RPE65, ezrin, and BEST1 proteins. On filter, the LEPI cells develop tighter barrier than the ex vivo bovine RPE-choroid: permeability coefficients of beta-blockers (atenolol, nadolol, timolol, pindolol, metoprolol, betaxolol) ranged from 0.4 × 10−6 cm/sec to 2.3 × 10−6 cm/sec depending on the drug lipophilicity. This rapidly differentiating cell line will be an asset in ocular studies since it is easily maintained, it grows and differentiates quickly and does not require specialized culture conditions for differentiation. Thus, this cell line is suitable for both small scale assays and high throughput screening in drug discovery and development.
Circulating CTRP6 Levels are Increased in Overweight or Obese Chinese Individuals and Associated with Insulin Resistance Parameters: A Pilot Study

Abstract Aims CTRP6, a newly discovered adipokine, has been found to be a regulator for energy homeostasis. However, the association between circulating CTRP6 and obesity in humans is still unclear. Methods 256 individuals, including 185 overweight/obese (OW/OB) and 71 normal weight adults, were recruited for this study. Circulating concentrations of CTRP6 and adiponectin (Adipoq) were examined by ELISA. Results Serum CTRP6 levels in obese individuals were significantly increased compared with those in healthy individuals (506.1±134.9 vs.363.3±80.5 ng/mL, P<0.01). Conversely, serum Adipoq concentrations in OW/OB individuals were markedly decreased compared with healthy controls [20.8 (12.1–29.3) vs. 14.1 ( 8.61–17.7) ; P<0.01]. Correlation analysis revealed that there was a positive relationship between circulating CTRP6 and age, BMI, Fat%, LDL-C, TG, WHR, TC, FBG, FIns, HOMA-IR and HbA1c, but there was an inverse correlation with Adipoq and HDL-C. Logistic regression analysis revealed that high serum CTRP6 levels are markedly associated with OW/OB. Finally, ROC curve analysis showed that the cut-off value for serum CTRP6 for prediction of IR is 518 ng/mL. Conclusions CTRP6 may be a marker related to OW/OB.