Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute and delayed peripheral and central neuromuscular alterations induced by a short and intense downhill trail run

Downhill sections are highly strenuous likely contributing to the development of neuromuscular fatigue in trail running. Our purpose was to investigate the consequences of an intense downhill trail run (DTR) on peripheral and central neuromuscular fatigue at knee extensors (KE) and plantar flexors (PF). Twenty‐three runners performed a 6.5‐km DTR (1264‐m altitude drop) as fast as possible. The electromyographic activity of vastus lateralis (VL) and gastrocnemius lateralis (GL) was continuously recorded. Neuromuscular functions were assessed Pre‐, Post‐, and 2‐day Post‐DTR (Post2d). Maximal voluntary torques decreased Post (∼ −19% for KE, ∼ −25% for PF) and Post2d (∼ −9% for KE, ∼ −10% for PF). Both central and peripheral dysfunctions were observed. Decreased KE and PF voluntary activation (VA), evoked forces, VL M‐wave amplitude, and KE low‐frequency fatigue were observed at Post. Changes in VL M‐wave amplitude were negatively correlated to VL activity during DTR. Changes in PF twitch force and VA were negatively correlated to GL activity during DTR. The acute KE VA deficit was about a third of that reported after ultramarathons, although peripheral alterations were similar. The prolonged force loss seems to be mainly associated to VA deficit likely induced by the delayed inflammatory response to DTR‐induced ultrastructural muscle damage.
Central and peripheral hemodynamics in exercising humans: leg vs arm exercise

In humans, arm exercise is known to elicit larger increases in arterial blood pressure (BP) than leg exercise. However, the precise regulation of regional vascular conductances (VC) for the distribution of cardiac output with exercise intensity remains unknown. Hemodynamic responses were assessed during incremental upright arm cranking (AC) and leg pedalling (LP) to exhaustion (Wmax) in nine males. Systemic VC, peak cardiac output (Qpeak) (indocyanine green) and stroke volume (SV) were 18%, 23%, and 20% lower during AC than LP. The mean BP, the rate‐pressure product and the associated myocardial oxygen demand were 22%, 12%, and 14% higher, respectively, during maximal AC than LP. Trunk VC was reduced to similar values at Wmax. At Wmax, muscle mass‐normalized VC and fractional O2 extraction were lower in the arm than the leg muscles. However, this was compensated for during AC by raising perfusion pressure to increase O2 delivery, allowing a similar peak VO2 per kg of muscle mass in both extremities. In summary, despite a lower Qpeak during arm cranking the cardiovascular strain is much higher than during leg pedalling. The adjustments of regional conductances during incremental exercise to exhaustion depend mostly on the relative intensity of exercise and are limb‐specific.
MR imaging of protein folding in vitro employing Nuclear‐Overhauser‐mediated saturation transfer

MR Z‐spectroscopy allows enhanced imaging contrast on the basis of saturation transfer between the proton pools of cellular compounds and water, occurring via chemical exchange (chemical exchange saturation transfer, CEST) or dipole–dipole coupling (nuclear Overhauser effect, NOE). In previous studies, signals observed in the aliphatic proton region of Z‐spectra have been assigned to NOEs between protons in water molecules and protons at the surface of proteins. We investigated a possible relationship between the signal strength of NOE peaks in Z‐spectra obtained at B0 = 7 T and protein structure. Here, we report a correlation of NOE‐mediated saturation transfer with the structural state of bovine serum albumin (BSA), which was monitored by fluorescence spectroscopy. Encouraged by CEST signal changes observed in tumor tissue, our observation also points to a possible contrast mechanism for MRI sensitive to the structural integrity of proteins in cells. Therefore, protein folding should be considered as an additional property affecting saturation transfer between water and proteins, in combination with the microenvironment and physiological quantities, such as metabolite concentration, temperature and pH. Copyright © 2013 John Wiley & Sons, Ltd.
Terlipressin or norepinephrine in hyperdynamic septic shock: A prospective, randomized study*

Objective:To compare, in patients with hyperdynamic septic shock, the effects of norepinephrine or terlipressin on hemodynamic variables and renal function. Design:Prospective, randomized, open-label study. Setting:Intensive care unit of a university, tertiary, and referral center. Patients:Twenty adult patients with hyperdynamic septic shock, after fluid resuscitation. Interventions:Patients were randomized to receive norepinephrine or terlipressin. Global hemodynamic variables, oxygen consumption, urine flow, creatinine clearance, and arterial blood lactate levels were measured. Measurements and Main Results:Mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work were significantly increased with both drugs. With terlipressin, but not with norepinephrine, a significant decrease in heart rate (from 113 ± 17 to 104 ± 11 beats·min−1, p < .01) and cardiac index (from 5.1 ± 1.7 to 4.2 ± 1.6 L·min−1·m−2) was observed, with no change in stroke volume. Oxygen delivery index (from 784 ± 131 to 701 ± 92 mL·min−1·m−2) and consumption index (from 244 ± 69 to 210 ± 54 mL·min−1·m−2) were significantly decreased with terlipressin, but not with norepinephrine. Blood lactate concentrations were significantly decreased with both drugs. Urine flow and creatinine clearance were increased with both drugs. Conclusions:In patients with hyperdynamic septic shock, both norepinephrine and terlipressin were effective to raise mean arterial blood pressure. With terlipressin, but not norepinephrine, the improvement in blood pressure was achieved at the expense of cardiac index and oxygen consumption, which were significantly decreased. Renal function was improved with both drugs. In further studies, alternative strategies to maintain cardiac index should be explored, such as a synergy between low-dose terlipressin and dobutamine.
Assessment of GABAA benzodiazepine receptor (GBzR) sensitivity in patients with alcohol dependence.

AIM The aim of this study was to measure GABAA benzodiazepine receptor (GBzR) sensitivity in alcohol-dependent patients and compare with matched non-dependent drinkers. METHODS Nine abstinent alcohol-dependent male patients, age matched with nine male non-dependent social drinkers, received an intravenous infusion of midazolam. Objective (saccadic eye movement slowing) and subjective (visual analogue scales) measurements were recorded at 15-min intervals for 2 h. RESULTS There were no differences in objective or subjective measures. CONCLUSIONS Our hypothesis that patients with alcohol dependence would have less slowing of their eye movements in response to this challenge, reflecting reduced GBzR sensitivity, was not confirmed. The reasons for this could mean that GBzR function returns to normal with abstinence, or that this paradigm is unable to measure the subtle subtype-specific changes in GBzR sensitivity that occur following dependent alcohol use.
Training Loads for the Development of Lower Body Muscular Power During Squatting Movements

THE SELECTION OF TRAINING LOADS FOR THE DEVELOPMENT OF MUSCULAR FORCE AND POWER FOR ATHLETIC PERFORMANCE IS CURRENTLY AN AREA OF MUCH INTEREST AMONG BOTH STRENGTH AND CONDITIONING PRACTITIONERS AND SPORTS SCIENTISTS. THIS ARTICLE REVIEWS THE RESULTS OF TRAINING STUDIES USING SQUAT AND JUMP SQUAT MOVEMENTS IN AN ATTEMPT TO CLARIFY THE PRACTICAL APPLICATION OF RESEARCH FINDINGS TO LOAD PRESCRIPTION FOR THE DEVELOPMENT OF ATHLETIC PERFORMANCE.
Widespread endotheliopathy in adults with cyanotic congenital heart disease

Abstract Introduction: Cyanotic congenital heart disease is associated with functional limitation and vascular events. The nature and extent of endothelial dysfunction in cyanotic adults is poorly understood. We sought to characterise endothelial function in this setting. Methods: A total of fourteen adults with cyanotic congenital heart disease (40±3 years) together with age- and sex-matched healthy controls underwent assessment of nitric oxide-dependent vascular responses, including flow-mediated dilatation of the brachial artery and dynamic vessel analysis of the retina in response to flickering light. Plasma levels of the endothelium-derived vasoconstrictor endothelin-1 and the nitric oxide antagonist, asymmetric dimethylarginine, were measured. Circulating endothelial progenitor cells were assessed by flow cytometry. Results: Flow-mediated dilatation was significantly lower in cyanosed adults than controls (4.0±0.8 versus 7.2±1.0%, p=0.019, n=11 per group). Retinal arterial and venous dilatory responses were also impaired (2.9±0.8 versus 5.0±0.6%, p=0.05 and 3.4±0.3 versus 5.2±0.7%, p=0.04, n=13). Serum levels of endothelin-1 and asymmetric dimethylarginine were higher in cyanosed adults (3.0±0.6 versus 1.1±0.1 pg/ml, p=0.004 and 0.68±0.05 versus 0.52±0.02 μmol/L, p=0.03, n=11). Endothelial progenitor cells (CD34+CD45dimCD133+KDR+) were reduced in those with chronic cyanosis (17±4 versus 40±6 per million white blood cells, p=0.005, n=11). Conclusions: Endothelial function is impaired in the systemic arteries and retinal vessels in adults with cyanotic congenital heart disease, suggesting a widespread endotheliopathy. Diminished numbers of endothelial progenitor cells might potentially contribute to these observations.
Acquired long QT interval complicated with Torsades de Pointes as presentation of a pheochromocytoma in a paediatric patient: a case report

Abstract Torsades de Pointes is an extremely rare arrhythmia in children associated to LQT syndrome. Pheochromocytomas are also extremely rare tumours in the paediatric age. We present a case of a young patient with an acquired long QT syndrome complicating with Torsades de Pointes as first clinical manifestation of a pheochromocytoma.
Post‐contrast myocardial T1 and ECV disagree in a longitudinal canine study

Both post‐contrast myocardial T1 and extracellular volume (ECV) measurements have been associated with diffuse interstitial fibrosis. The cardiovascular magnetic resonance (CMR) field is migrating towards ECV, because it is largely insensitive to confounders that affect post‐contrast myocardial T1. Despite the theoretical advantages of myocardial ECV over post‐contrast myocardial T1, systematic experimental studies comparing the two measurements are largely lacking. We sought to measure the temporal changes in post‐contrast myocardial T1 and ECV in an established canine model with chronic atrial fibrillation.
In vivo detection of the effects of preconditioning on LNCaP tumors by a TNF‐α nanoparticle construct using MRI

The outcome of systemic and local therapies (e.g. chemotherapy, radiotherapy, surgery, focal ablation) for prostate cancer can be significantly improved by using tumor‐specific adjuvants prior to treatment (“preconditioning”). We propose to use dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI) to monitor the in vivo response of a mouse model of prostate cancer treated with a vascular disruptive agent, TNF‐α, delivered on a gold nanoparticle (NP‐TNF). Six male nude mice bearing 4–5 week old LNCaP tumors were scanned at 9.4 T. DCE‐MRI was performed two days before and 4–5 h after treatment with NP‐TNF. An intraperitoneal (i.p.) bolus of gadolinium‐DTPA (Gd) was administered and contrast enhancement was measured for 90 min. Concentration–time curves of Gd were calculated and the area under the Gd curve (AUGC) was determined pre‐ and post‐treatment. NP‐TNF treatment caused an increase in contrast uptake in tumors. Interestingly, the early concentration (10 min post Gd bolus i.p.) was similar in both untreated and treated conditions; however, 90 min after injection, [Gd] was 3.4 times higher than before treatment. AUGC doubled from (11 ± 6) [Gd] × min before treatment to (22 ± 9) [Gd] × min after treatment. An increase in signal enhancement was also observed in the muscle but to a lesser degree. We also evaluated the kinetics of intravenous Gd administration in mice bearing a jugular vein catheter to mimic the delivery method used in clinical trials. The overall treatment effects were independent of the delivery pathway of the contrast agent. In conclusion, we show that DCE‐MRI is suitable to detect changes associated with a vascular disruptive agent in a mouse model of prostate cancer. The ability to characterize the effects of nanoparticle therapy in vivo with non‐destructive methods is important, as such compounds, in combination with treatment strategies, are progressing towards clinical trials. Copyright © 2014 John Wiley & Sons, Ltd.
Cardiac complications in childhood cancer survivors treated with anthracyclines*

Abstract Cardiovascular complications are among the leading causes of morbidity and mortality among survivors of childhood cancer, after cancer relapse and secondary malignancies. Although advances in cancer treatment have improved the 5-year survival rates, the same treatments, such as anthracyclines, that cure cancer also increase the risk for adverse cardiovascular effects. Anthracycline-related cardiotoxicity in survivors of childhood cancer is progressive and can take years to develop, initially presenting as sub-clinical cardiac abnormalities that, if left undetected or untreated, can lead to heart failure, myocardial infarction, or other clinical cardiac dysfunction. A higher cumulative dose of anthracycline is associated with cardiotoxicity in children; however, sub-clinical cardiac abnormalities are evident at lower doses with longer follow-up, suggesting that there is no “safe” dose of anthracycline. Other risk factors include female sex, younger age at diagnosis, black race, trisomy 21, longer time since treatment, and the presence of pre-existing cardiovascular disease and co-morbidities. Cardioprotective strategies during treatment are limited in children. Enalapril provides only temporary cardioprotection, whereas continuous anthracycline infusion extends none. On the other hand, dexrazoxane successfully prevents or reduces anthracycline-related cardiotoxicity in children with cancer, without increased risks for recurrence of primary or second malignancies or reductions in anti-tumour efficacy. With more childhood cancer survivors now reaching adulthood, it is vital to understand the adverse effects of cancer treatment on the cardiovascular system and their long-term consequences to identify and establish optimal prevention and management strategies that balance oncologic efficacy with long-term safety.
Metachromatic Leukodystrophy – An Update

Metachromatic leukodystrophy (MLD) is a rare lysosomal sphingolipid storage disorder, caused by a deficiency of arylsulfatase A (ASA). It is inherited in an autosomal recessive way, among Caucasians three causing alleles are frequent. Demyelination is the hallmark of MLD. Interest in the disease has increased as therapeutic options such as stem cell transplantation, enzyme replacement and gene therapy are topics of current research. A late-infantile (onset before 3 years of age), a juvenile form (onset before 16 years) and an adult form are usually distinguished. Rapid motor decline is typical for the first and also the second forms, the second may be preceded by cognitive and behavioural problems, which mainly characterize the adult form. There is evidence for a genotype-phenotype correlation: patients homozygous for alleles which do not allow the expression of any enzyme activity (null-allele) suffer from the late infantile form; heterozygosity for a null allele and a non-null allele are more associated with the juvenile form and homozygosity for non-null alleles is more frequent in the most attenuated adult onset form.
Assessment of type II diabetes mellitus drug therapy in diabetes clinic of a tertiary care teaching hospital in Addis Ababa

Background: Prevalence of type II diabetes mellitus(T2DM) is substantially increasing in Ethiopia but there are no studies on its drug therapy. Objective: To assess drug therapy for T2DM and check association between fasting blood glucose levels with patient demographics, clinical characteristics and medications. Materials and Methods: A cross-sectional institution based study was conducted on T2DM patients over a 1 month period using patient chart review and key informant interview at the diabetes clinic of Tikur Anbessa Specialized Hospital (TASH). Results: Of 103 patients enrolled females accounted 59.2%. The mean age was 52.2 years and 96.12% of patients were from Addis Ababa. The mean fasting blood glucose (FBG) and body mass index (BMI) were 155.99 mg/dl and 26.4 kg/m 2 respectively. About 51.45% of the patients were overweight; and neutral protamine hagedorn insuline (NPH) (56.3%), metformin plus glibenclamide (19.4%) and metformin (10.7%) were the most common drug therapies. But there was no significant association of FBG levels of patients with either, gender, age, BMI or medications. Conclusions: The drug therapy at the diabetes clinic was in line with recommendations of International Diabetes Federation (IDF)despite lack of uniform guideline.
Executive function deficits in congenital heart disease: why is intervention important?

Abstract It is widely recognised that children with congenital heart disease (CHD) are at high risk for neurodevelopmental impairments including attention deficit hyperactivity disorder and autism spectrum disorder symptoms. Executive function impairments are one of the most prominent neurodevelopmental features associated with CHD. These deficits can have widespread debilitating repercussions in children’s neurocognitive, behavioural, and psycho-social development. There is a crucial gap in research regarding the efficacy of preventive or treatment strategies for these important cognitive morbidities. Executive functions are complex neurocognitive skills highly amenable to improvement. Evidence-based interventions have shown promising results in other paediatric populations, strongly suggesting that they might also benefit the growing population of children with CHD. In this review, we summarise the available data on executive function impairments in children and adolescents with CHD. We underline the important co-morbidity of executive dysfunction with other cognitive and psychiatric issues in CHD, which raises awareness of the crucial need to prevent or at least mitigate these deficits. Finally, we summarise future avenues for research in terms of interventions that may help reduce executive function impairments in youth with CHD.
Influence of a 2‐ to 6‐year physical education intervention on scholastic performance: The CHAMPS study‐DK

The aim of this study was to investigate the influence of a school‐based intervention with a tripling of physical education (PE) lessons from two (90 minutes) to six lessons per week (270 minutes) on scholastic performance. This study is part of the CHAMPS study‐DK, a quasi‐experimental study that began in 2008. The intervention group consisted of six schools, and the control group consisted of four matched schools (mean age at baseline=8.4 years, kindergarten class fourth grade). Academic performance was extracted from the national test system from 2010 to 2014 (Math and Danish were measured at third and sixth, and second, fourth and sixth grades, respectively). Participants included 1888 students participating in at least one scholastic performance test. Linear mixed models were applied to test for differences between groups and adjusted for known confounders. No significant differences were observed between groups in the academic performance tests (control group reference); Danish second grade β=−1.34 (95% CI −9.90, 7.22), fourth grade β=0.22 (95% CI −6.12, 6.56), sixth grade β=1.03 (95% CI −5.02, 7.08), and all grades combined β=0.28 (95% CI −5.74, 6.31) and Math third grade β=−2.87 (95% CI −9.65, 3.90), sixth grade β=0.99 (95% CI −7.36, 9.34) and combined β=−1.20 (95% CI −8.10, 5.71). In conclusion, no significant differences were observed between intervention and control schools for scholastic performance. Importantly, there were no negative effects of additional PE on scholastic outcomes, despite more PE and longer school days for intervention children.
Development of a nutrition knowledge questionnaire for young endurance athletes and their coaches

Both athletes and coaches should have adequate nutrition knowledge to understand the importance of diet on athletic performance, recovery, and health. Nutrition knowledge can be assessed reliably only by validated knowledge questionnaires. The aim of this study was to develop a reliable and valid questionnaire for assessing the nutrition knowledge of young endurance athletes and their coaches. The questionnaire was developed with an expert panel and pilot tested by athletes, coaches, and students. Content, face, and construct validities both as test‐retest reliability and internal consistency reliability were ensured when the current questionnaire was developed. Athletes (n = 16) and coaches (n = 13) pilot tested the 127‐item questionnaire. After item analysis and proposals from the expert panel, 41 items were removed. Internal consistency of the 86‐item questionnaire in the pilot study was 0.87, measured using Cronbach's α. Construct validity was evaluated by the difference in knowledge between nutrition (n = 20) and humanities students (n = 22). Nutrition students had significantly higher knowledge scores (P < .001). Test‐retest reliability for all knowledge sections between those groups was 0.85 measured using Pearson's r. Final adjustments to the questionnaire were made on the grounds of feedback from the respondents and proposals from the experts (n = 6). These adjustments resulted in minor changes in the construct of the items, the layout of the questionnaire, and the removal of 7 items. The final questionnaire had 79 items. The questionnaire can be used to measure the overall nutrition knowledge of endurance athletes and their coaches and to find potential gaps in nutrition knowledge.
Mechanisms of T2* anisotropy and gradient echo myelin water imaging

In MRI, structurally aligned molecular or micro‐organization (e.g. axonal fibers) can be a source of substantial signal variations that depend on the structural orientation and the applied magnetic field. This signal anisotropy gives us a unique opportunity to explore information that exists at a resolution several orders of magnitude smaller than that of typical MRI. In this review, one of the signal anisotropies, T2* anisotropy in white matter, and a related imaging method, gradient echo myelin water imaging (GRE‐MWI), are explored. The T2* anisotropy has been attributed to isotropic and anisotropic magnetic susceptibility of myelin and compartmentalized microstructure of white matter fibers (i.e. axonal, myelin, and extracellular space). The susceptibility and microstructure create magnetic frequency shifts that change with the relative orientation of the fiber and the main magnetic field, generating the T2* anisotropy. The resulting multi‐component magnitude decay and nonlinear phase evolution have been utilized for GRE‐MWI, assisting in resolving the signal fraction of the multiple compartments in white matter. The GRE‐MWI method has been further improved by signal compensation techniques including physiological noise compensation schemes. The T2* anisotropy and GRE‐MWI provide microstructural information on a voxel (e.g. fiber orientation and tissue composition), and may serve as sensitive biomarkers for microstructural changes in the brain. Copyright © 2016 John Wiley & Sons, Ltd.