Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis.

IMPORTANCE No current therapy for relapsing-remitting multiple sclerosis (MS) results in significant reversal of disability. OBJECTIVE To determine the association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability and other clinical outcomes in patients with MS. DESIGN, SETTING, AND PARTICIPANTS Case series of patients with relapsing-remitting MS (n = 123) or secondary-progressive MS (n = 28) (mean age, 36 years; range, 18-60 years; 85 women) treated at a single US institution between 2003 and 2014 and followed up for 5 years. Final follow-up was completed in June 2014. INTERVENTIONS Treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells. MAIN OUTCOMES AND MEASURES Primary end point was reversal or progression of disability measured by change in the Expanded Disability Status Scale (EDSS) score of 1.0 or greater (score range, 0-10). Secondary outcomes included changes in the Neurologic Rating Scale (NRS) score of 10 or greater (score range, 0-100), Multiple Sclerosis Functional Composite (MSFC) score, quality-of-life Short Form 36 questionnaire scores, and T2 lesion volume on brain magnetic resonance imaging scan. RESULTS Outcome analysis was available for 145 patients with a median follow-up of 2 years and a mean of 2.5 years. Scores from the EDSS improved significantly from a pretransplant median of 4.0 to 3.0 (interquartile range [IQR], 1.5 to 4.0; n = 82) at 2 years and to 2.5 (IQR, 1.9 to 4.5; n = 36) at 4 years (P < .001 at each assessment). There was significant improvement in disability (decrease in EDSS score of ≥1.0) in 41 patients (50%; 95% CI, 39% to 61%) at 2 years and in 23 patients (64%; 95% CI, 46% to 79%) at 4 years. Four-year relapse-free survival was 80% and progression-free survival was 87%. The NRS scores improved significantly from a pretransplant median of 74 to 88.0 (IQR, 77.3 to 93.0; n = 78) at 2 years and to 87.5 (IQR, 75.0 to 93.8; n = 34) at 4 years (P < .001 at each assessment). The median MSFC scores were 0.38 (IQR, -0.01 to 0.64) at 2 years (P < .001) and 0.45 (0.04 to 0.60) at 4 years (P = .02). Total quality-of-life scores improved from a mean of 46 (95% CI, 43 to 49) pretransplant to 64 (95% CI, 61 to 68) at a median follow-up of 2 years posttransplant (n = 132) (P < .001). There was a decrease in T2 lesion volume from a pretransplant median of 8.57 cm3 (IQR, 2.78 to 22.08 cm3) to 5.74 cm3 (IQR, 1.88 to 14.45 cm3) (P < .001) at the last posttransplant assessment (mean follow-up, 27 months; n = 128). CONCLUSIONS AND RELEVANCE Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes. These preliminary findings from this uncontrolled study require confirmation in randomized trials.
Pathogenesis of wound healing disorders in the elderly

The elderly constitute the age group most susceptible to wound healing disorders and chronic wounds, the most prevalent being venous leg ulcers, pressure ulcers, and diabetic foot ulcers. However, other age‐associated diseases should also be taken into consideration in the diagnostic workup of chronic wounds, and not be underestimated. A better understanding of the pathomechanisms involved in the wound healing process is of key importance in combatting the difficulties associated with the treatment of chronic wounds. In recent decades, considerable progress has been made in the development of pioneering therapeutic strategies for chronic wounds. In this context, the use of growth factors and cytokines, tissue engineering, and cell therapy – including stem cells – have proven very promising. Nevertheless, prior to their introduction into routine clinical practice, large controlled clinical trials are required to assess the safety of these techniques.
Dental Considerations in Obstructive Sleep Apnea Patients: A review

Upper airway sleep disorders are becoming recognized common medical concerns. The management and treatment of obstructive sleep apnea patients have long since been addressed by medical personals. Recently, dental participation in management of the patients through oral devices has been accepted as a recommended treatment modality by the American Sleep Disorders Association. As dental professionals, we have significant role to play in the early diagnosis, management and care of patients suffering from sleep apnea. This article reviews the etiology, clinical features, management and dental perspective of obstructive sleep apnea.
Is big data the new frontier for academic-industry collaboration?

Academic-industry research collaborations have long been a source of controversy in medicine. Advocates suggest that collaborations can focus academic researchers on important clinical and translational research problems and provide them with financial and capability-enhancing technical resources.1 Critics maintain that industry engagement distracts from, or distorts, the teaching and research missions of academia.2 Although regulatory and compliance frameworks have been established to govern these relationships, controversy continues to surround efforts to enhance industry and academia collaborations.
Role of electrical storm as a mortality and morbidity risk factor and its clinical predictors: a meta-analysis.

AIMS Electrical storm (ES) is a devastating and life-threatening event in clinical practice, but its real weight as a risk factor and its clinical predictors remain unclear. Our objective was to evaluate ES as a mortality and morbidity risk factor and to define the clinical variables associated with ES. METHODS AND RESULTS The meta-analysis was performed according to the PRISMA guidelines. At the end of the selection process, 13 studies were collected and included in the quantitative analysis. Mortality and morbidity due to ES were assessed. The most acknowledged ES predictors were taken into account in separate sub-analyses. The whole cohort included 5912 patients (857 with ES). Risk of death was increased in the ES group [risk ratio (RR) 3.15; 95% confidence interval (CI) 2.22-4.48]. Electrical storm was also associated with increased composite risk of all-cause death, cardiac transplantation, and hospitalization for acute heart failure (RR 3.39; 95% CI 2.31-4.97). These results were confirmed by comparing the ES group with patients with or without previous unclustered episodes of ventricular arrhythmias. Moreover, implantable cardioverter-defibrillator (ICD) for secondary prevention, lower ejection fraction, monomorphic ventricular tachycardia as triggering arrhythmia, and class I anti-arrhythmic drugs therapy were all associated with ES. CONCLUSION Electrical storm is a strong mortality risk factor and it is associated with an increased combined risk of death, heart transplantation, and hospitalization for heart failure. Implantable cardioverter-defibrillator for secondary prevention, monomorphic ventricular tachycardia as triggering arrhythmia, lower ejection fraction, and class I anti-arrhythmic drugs therapy are all associated with ES and could be used to define specific populations with higher risk to develop ES.
Increased risk of atrial fibrillation and stroke during active stages of inflammatory bowel disease: a nationwide study.

AIMS Inflammation is considered to play a role in the development of atrial fibrillation (AF). Hence inflammatory bowel disease (IBD) may be associated with AF. We therefore examined the incidence of AF and stroke in patients with IBD. METHODS AND RESULTS From Danish nationwide registries 1996-2011, we identified 24 499 patients with new-onset IBD and 236 275 age- and sex-matched controls. Poisson regression analyses with continuously updated covariates were used to estimate incidence rate ratios (IRRs) of AF and stroke. Disease activity stages of flare (new disease activity), persistent activity, and remission were defined by corticosteroid prescriptions, IBD hospital admissions, and biological treatment. Inflammatory bowel disease patients had a mean age of 43.9 years, 53.9% were women, and mean follow-up was 6.8 years. Among IBD patients, 685 had AF and 549 had a stroke, corresponding to incidence rates per 1000 person-years of 4.16 vs. 2.70 for AF and 3.33 vs. 2.44 for stroke, compared with matched controls. Overall IBD-associated risk of AF corresponded to IRR 1.26 (1.16-1.36), but was driven by increased AF incidence during IBD flares [IRR 2.63 (2.26-3.06)] and persistent activity [IRR 2.06 (1.67-2.55)], whereas no increased AF risk was observed in remission periods [IRR 0.97 (0.88-1.08)]. Likewise increased stroke risk was exclusively found during active IBD [IRRs: 1.57 (1.27-1.93), 1.71 (1.32-2.21), and 1.04 (0.93-1.15) for flares, persistent activity, and remission, respectively]. CONCLUSION Active IBD is associated with increased risk of AF and stroke. These findings may be relevant to clinical practice.
Regulation of endometrial repair and its impact on heavy menstrual bleeding

ii Declaration . iv Acknowledgements . v Abbreviations . vi Publications . ix Presentations and Prizes . x 1. Literature Review. 1 1.1 The Human Endometrium and Menstrual Cycle . 2 1.1.1 The ovarian cycle . 2 1.1.2 Endometrial histology . 4 1.1.3 Menstrual phase . 6 1.1.4 Proliferative phase. 6 1.1.5 Secretory phase . 6 1.2 Menstruation as an inflammatory process . 8 1.2. 1 Leukocytes . 8 1.2. 2 Chemokines. 9 1.2. 3 Prostaglandins . 9 1.2. 4 Nuclear factor-κB. 11 1.3 The processes involved in endometrial repair . 12 1.3. 1 Inflammation. 12 1.3. 2 Resolution of Inflammation . 13 1.3. 3 Tissue formation . 15 1.3. 4 Tissue remodelling. 17 1.3. 5 Angiogenesis . 18 1.4 The regulation of endometrial repair . 23 1.4. 1 Oestradiol . 23 1.4. 2 Progesterone and its withdrawal . 26 1.5 The role of hypoxia in repair. 29 1.5. 1 Evidence for the presence of endometrial hypoxia . 29
ASSESSMENT OF KNOWLEDGE OF EPILEPSY IN EPILEPTIC PATIENTS ATTENDING A TERTIARY CARE CENTRE IN KERALA, INDIA

Objective : Patient’s knowledge of his/her disease plays a vital role in epilepsy care. Studies assessing epileptic patient’s knowledge of epilepsy have not been done in the state of Kerala, South India, which is distinguished from the rest of India by the high level of literacy and health awareness. The study results can lead to suggestions for appropriate intervention strategies for epileptic patients. Methods: A prospective, observational study was carried out in the department of neurology at Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India. Newly referred patients fulfilling the inclusion and exclusion criteria were enrolled in the study. A 15-item validated questionnaire was used to assess patient’s awareness of epilepsy, safety aspects, social issues and treatment. Results: 105 epileptic patients with a mean age of 34.4±14.66 years were enrolled in the study. A high percentage of correct responses were observed in relation to epilepsy as not a mental (74.4%), hereditary (74.3%) or contagious disease (95.2%). Encouraging responses were also obtained regarding confidence in leading a married life (77.1%), overall capability of epileptic patients compared to others (77.1%) and the possibility of epilepsy being controlled with treatment (83.8%). Correct responses on safety issues (40.9%), first aid measures (12.3%), driving (31.4%) and swimming (29.5%) were poor. 47.6% of patients feared from the side effects of anti-epileptic drug treatment and only 3.8% were knowledgeable about epilepsy treatment options other than that with medications. Conclusion: The patients in our study had a basic understanding of epilepsy, but knowledge in terms of safety measures, social issues and treatment options were poor. Educational interventions by health care professionals should focus on these facets of epilepsy apart from the general aspects. Keywords: Assessment, Knowledge of epilepsy, Questionnaire method.
Proportion of US adults potentially affected by the 2014 hypertension guideline.

IMPORTANCE The new 2014 blood pressure (BP) guideline released by the panel members appointed to the Eighth Joint National Committee (JNC 8; 2014 BP guideline) proposed less restrictive BP targets for adults aged 60 years or older and for those with diabetes and chronic kidney disease. OBJECTIVE To estimate the proportion of US adults potentially affected by recent changes in recommendations for management of hypertension. DESIGN Cross-sectional, nationally representative survey. PARTICIPANTS Using data from the National Health and Nutrition Examination Survey between 2005 and 2010 (n = 16,372), we evaluated hypertension control and treatment recommendations for US adults. MAIN OUTCOMES AND MEASURES Proportion of adults estimated to meet guideline-based BP targets under the 2014 BP guideline and under the previous seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guideline. RESULTS The proportion of younger adults (18-59 years) with treatment-eligible hypertension under the JNC 7 guideline was 20.3% (95% CI, 19.1%-21.4%) and decreased to 19.2% (95% CI, 18.1%-20.4%) under the 2014 BP guideline. Larger declines were observed among older adults (≥60 years), decreasing from 68.9% (95% CI, 66.9%-70.8%) under JNC 7 to 61.2% (95% CI, 59.3%-63.0%) under the 2014 BP guideline. The proportion of adults with treatment-eligible hypertension who met BP goals increased slightly for younger adults, from 41.2% (95% CI, 38.1%-44.3%) under JNC 7 to 47.5% (95% CI, 44.4%-50.6%) under the 2014 BP guideline, and more substantially for older adults, from 40.0% (95% CI, 37.8%-42.3%) under JNC 7 to 65.8% (95% CI, 63.7%-67.9%) under the 2014 BP guideline. Overall, 1.6% (95% CI, 1.3%-1.9%) of US adults aged 18-59 years and 27.6% (95% CI, 25.9%-29.3%) of adults aged 60 years or older were receiving BP-lowering medication and meeting more stringent JNC 7 targets. These patients may be eligible for less stringent or no BP therapy with the 2014 BP guideline. CONCLUSIONS AND RELEVANCE Compared with the JNC 7 guideline, the 2014 BP guideline from the panel members appointed to the JNC 8 was associated with a reduction in the proportion of US adults recommended for hypertension treatment and a substantial increase in the proportion of adults considered to have achieved goal BP, primarily in older adults.
Hábitos de merienda en escolares de nuestro medio: estudio HABIMER Plus

Introduccion: los habitos alimentarios adquiridos en la edad escolar son el molde que se reproducira en la edad adulta. La merienda debe constituir el 15-20% de las calorias diarias, y es una buena oportunidad para administrar frutas, lacteos y cereales. Objetivo: conocer los habitos alimentarios en la merienda de ninos escolares entre 6 y 12 anos. Material y metodos: evaluacion de los habitos de merienda de los ninos de 6-12 anos en un colegio de la Comunidad Autonoma de Madrid. Se realizo una encuesta a los ninos sobre los habitos en la merienda de los tres ultimos dias. Los resultados se analizaron en el programa SPSS®. Resultados: se analizaron 214 encuestas, 104 pertenecientes a ninas y 107 a ninos. El 76% de los ninos merienda todos los dias. Este porcentaje disminuye hasta un 28 y un 20% en los ninos de 11 y 12 anos, respectivamente. El 60-69% refiere comer un bocadillo o sandwich; un 49%, fruta, y un 38,5%, bolleria industrial. En cuanto a los lacteos, el 94% ingiere algun tipo de lacteo; sin embargo, el 76% lo habia ingerido en forma de batidos, natillas o flanes. El 48% de los ninos acompano con agua su merienda, mientras que el 70,1% lo hizo con zumos envasados. Conclusiones: hay que hacer hincapie en los alimentos ofertados en la merienda, estableciendo medidas orientadas a recomendar mas frutas frescas en lugar de zumos envasados, de lacteos en forma de leche/yogur en lugar de batidos y flanes, y evitar el consumo de bolleria.
NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure.

AIMS The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. METHODS AND RESULTS An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF epicardial, midmyocardial, and endocardial cell variants. Affects of NS5806 were also included in HF models through its direct interaction with Kv4.3 and Kv1.4. Single-cell simulations performed in all models (control, HF, and HF + drug) and variants (epi, mid, and endo) assessed AP morphology and underlying ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease. The qualitative effects of application of half-maximal effective concentration (EC50) of NS5806 on APs and CaT are heterogeneous and non-linear. Deepening in the AP notch with drug is a direct effect of the activation of Ito; both Ito and consequent alteration of IK1 kinetics cause decrease in AP plateau potential. Decreased APD50 and APD90 are both due to altered IK1. Analysis revealed that drug effects depend on transmurality. Ca(2+) transient morphology changes-increased amplitude and shorter time to peak-are due to direct increase in ICa,L and indirect larger SR Ca(2+) release subsequent to Ito activation. CONCLUSIONS Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however, restoration of notch depth appears to impart modest benefit and a likelihood of therapeutic value in modulating early repolarization.
Fragmented QRS for the prediction of sudden cardiac death: a meta-analysis.

AIMS Risk stratification of sudden cardiac death (SCD) is challenging. Fragmented QRS (fQRS) is proposed as a non-invasive electrocardiogram marker associated with mortality and SCD. Results from individual studies including small numbers of patients are discrepant. We therefore performed a meta-analysis of studies evaluating fQRS as a risk stratification tool to predict all-cause mortality and SCD. METHODS AND RESULTS Electronic databases and bibliographies were systematically searched (1996-2014). Twelve studies (5009 patients) recruiting patients with coronary artery disease or non-ischaemic cardiomyopathy met our inclusion criteria. Fragmented QRS was associated with an all-cause mortality relative risk of 1.71 (CI 1.02-2.85) and a relative risk of SCD of 2.20 (CI 1.05-4.62). Subgroup analysis demonstrated greater mortality and SCD risk in those with left ventricular ejection fraction >35% and SCD risk in those with QRS duration <120 ms. CONCLUSION Fragmented QRS is associated with all-cause mortality and the occurrence of SCD and may be suited as a marker of SCD risk. The incremental benefit of fQRS should be assessed in a randomized, prospective setting.
Practical feeding and condition scoring for donkeys and mules

Summary Donkeys have evolved to thrive on highly fibrous, poor quality foodstuffs and have evolved as browsers as well as grazers. As such, they have different nutrient requirements with significantly lower energy and protein needs when compared with horses. Dietary management of donkeys is essential when kept in a temperate climate as they are prone to obesity and related disorders. A diet based on fibrous forages and limited grazing is usually sufficient for the majority of donkeys and mules. Specialist feeding is discussed in this article.
Trends in visits for traumatic brain injury to emergency departments in the United States.

In the last decade, traumatic brain injury (TBI) garnered increased attention, including public campaigns and legislation to increase awareness and prevent head injuries.1 The Centers for Disease Control and Prevention (CDC) describes TBI as a serious public health concern.2 We sought to describe national trends in emergency department (ED) visits for TBI.
National Institute for Health and Care Excellence 2014 guidance on cardiac implantable electronic devices: health economics reloaded.

The past decade has seen rapid progress in cardiac implantable electronic devices delivering implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). Proof-of-principle studies and single-centre clinical studies led to large randomized controlled trials (RCTs). As evidence has accumulated, clinical guideline groups have extended CRT and ICD indications to an increasing number of patients. For a significant proportion of patients with left ventricular dysfunction and/or at risk of sudden cardiac death, device therapy is now part of standard management. Modern healthcare requires expensive treatments to be scrutinized for cost-effectiveness as well as clinical efficacy. This is the only fair approach to the distribution of finite financial resources. As clinicians, we will always strive for the best possible treatment for each individual patient, without directly taking into account financial cost, but the ultimate responsibility for choosing what is to be funded lies with commissioners and politicians. While we are not exempt from a responsibility to use resources efficiently, we are very fortunate in cardiology that our clinically effective treatments have also proven to be cost-effective. Clinical guideline groups, including those of the European Society of Cardiology, do comment on cost-effectiveness, but guidelines are not generally issued on the basis of cost.1,2 In contrast, the United Kingdom's National Institute for Health and Care Excellence (NICE) does take into account health technology appraisals and cost-effectiveness analyses. In June 2014, new NICE guidance on ICD and CRT device implantation was published3 updating previous guidance from 2006 to 2007 ( Table 1 ). This editorial discusses this process of guideline development and the new data on which it is based. A unique aspect of the 2014 NICE guidelines was its adoption …
Promoting Nutrition for Men's Health

Morbidity and mortality are significantly higher in men than in women and are particularly related to lifestyle-related chronic diseases. Men tend to consume fewer vegetables and fruits than women and fail to meet recommendations for intakes of fats, fibers, and sodium. Men in some population groups tend to consume diets with lower nutrient density than women. Barriers to healthy eating in men include lack of awareness and personal interest, perceptions that foods and diets are “women's business,” lack of social support, and cynicism regarding nutrition messages by health authorities. In addition, many men perceive health-promoting foods as expensive, bland, nonsatiating, and time-consuming to prepare. Research specifically focused on men's health and nutrition is critically needed. Topics to be addressed include biological, psychological, and social correlates of healthy eating in men and nutritional factors particular to chronic disease risk reduction in men. Social, cultural, religious, economic, educational, and other aspects should be taken into account.