Miracle-dz/UniFAR-FTUs huggingface dataset:
Maintained peak leg and pulmonary VO2 despite substantial reduction in muscle mitochondrial capacity

We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low‐intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. Peak pulmonary VO2 (3.52 ± 0.18 L.min−1 pre vs 3.52 ± 0.19 post) and VO2 across the leg (2.8 ± 0.4L.min−1 pre vs 3.0 ± 0.2 post) were unchanged after the ski journey. Peak leg O2 delivery (3.6 ± 0.2 L.min−1 pre vs 3.8 ± 0.4 post), O2 extraction (82 ± 1% pre vs 83 ± 1 post), and muscle capillaries per mm2 (576 ± 17 pre vs 612 ± 28 post) were also unchanged; however, leg muscle mitochondrial OXPHOS capacity was reduced (90 ± 3 pmol.sec−1.mg−1 pre vs 70 ± 2 post, P < 0.05) as was citrate synthase activity (40 ± 3 μmol.min−1.g−1 pre vs 34 ± 3 vs P < 0.05). These findings indicate that peak muscle VO2 can be sustained with a substantial reduction in mitochondrial OXPHOS capacity. This is achieved at a similar O2 delivery and a higher relative ADP‐stimulated mitochondrial respiration at a higher mitochondrial p50. These findings support the concept that muscle mitochondrial respiration is submaximal at VO2max, and that mitochondrial volume can be downregulated by chronic energy demand.
Is cortisol involved in the alcohol-related fat mass impairment? A longitudinal clinical study.

AIMS Subjects with chronic alcohol abuse can present several metabolic and nutritional alterations. The hypothalamic-pituitary-adrenal (HPA) axis may play a role in these nutritional and metabolic disorders. The goal of this study was to investigate if there is any relationship between HP-hormones and metabolic and nutritional parameters in alcoholic subjects. METHODS Sixteen alcoholics were considered before and after 3 months of total alcohol abstinence. HP-related hormones were determined. Nutritional and metabolic parameters were assessed by dual-energy X-ray absorptiometry (DXA) and indirect calorimetry. RESULTS At baseline, a significant negative correlation was found between fat mass (FM) and cortisol (r = -0.54, P = 0.03). During abstinence, a significant increase of both body mass index (BMI) (P < 0.0001) and FM (P < 0.0001) was found at 12 weeks compared to baseline. A significant decrease of both plasma cortisol (P = 0.044) and aldosterone (P = 0.023) was found at 12 weeks compared to baseline. At 12 weeks, the significant correlation between cortisol and FM disappeared. CONCLUSIONS A higher HPA-axis activation-reflected by higher cortisol levels-was associated with a lower FM in alcoholics. Conversely, during total abstinence a reduced HPA-axis activity can play a role in the parallel nutritional recovery. The present results suggest a role of the HPA axis throughout cortisol both in the etiology of the alcohol-related nutritional alterations and in their recovery after a period of total alcohol abstinence.
Multi‐parametric MRI characterization of inflammation in murine skeletal muscle

Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi‐parametric, quantitative, non‐invasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi‐parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT‐MRI), and dynamic contrast enhanced (DCE‐MRI) parameters were calculated from data acquired in a single imaging session conducted 6–8 hours following the injection of λ‐carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi‐exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE‐MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed for other single or complex myopathy models. Copyright © 2014 John Wiley & Sons, Ltd.
Effects of velocity loss during resistance training on athletic performance, strength gains and muscle adaptations

We compared the effects of two resistance training (RT) programs only differing in the repetition velocity loss allowed in each set: 20% (VL20) vs 40% (VL40) on muscle structural and functional adaptations. Twenty‐two young males were randomly assigned to a VL20 (n = 12) or VL40 (n = 10) group. Subjects followed an 8‐week velocity‐based RT program using the squat exercise while monitoring repetition velocity. Pre‐ and post‐training assessments included: magnetic resonance imaging, vastus lateralis biopsies for muscle cross‐sectional area (CSA) and fiber type analyses, one‐repetition maximum strength and full load‐velocity squat profile, countermovement jump (CMJ), and 20‐m sprint running. VL20 resulted in similar squat strength gains than VL40 and greater improvements in CMJ (9.5% vs 3.5%, P < 0.05), despite VL20 performing 40% fewer repetitions. Although both groups increased mean fiber CSA and whole quadriceps muscle volume, VL40 training elicited a greater hypertrophy of vastus lateralis and intermedius than VL20. Training resulted in a reduction of myosin heavy chain IIX percentage in VL40, whereas it was preserved in VL20. In conclusion, the progressive accumulation of muscle fatigue as indicated by a more pronounced repetition velocity loss appears as an important variable in the configuration of the resistance exercise stimulus as it influences functional and structural neuromuscular adaptations.
Treatment for alcohol dependence in Catalonia: health outcomes and stability of drinking patterns over 20 years in 850 patients.

AIMS The aim of this study was to evaluate long-term outcomes in alcohol-dependent patients following outpatient treatment and gender differences in drinking outcome and mortality. METHODS A 20-year longitudinal prospective study was done with interim analyses at 1, 5 and 10 years. Of the original sample of 850 patients, 767 (90%) were located 20 years later and 393 of these were interviewed. 273 (32%) patients died during the intervening period and 101 (12%) no longer wished to participate in the study. Drinking status was assigned based on the 12 months prior to the follow-up interview. RESULTS At the 20-year follow-up, 277 (32.6%) of the 393 patients for whom drinking status could be assigned were abstinent (defined never drinking or drinking on less than occasion per month and never more than four drinks/drinking occasion.), 29 (3.4%) were controlled drinkers and 87 (10.2%) were heavy drinkers. Controlled drinking was the least stable category, with 23% continuing from year 5 to year 10 in that category, and 10% continuing in that category from year 10 to year 20. Mortality was higher (39.1%) in those who had been categorized at year 5 as heavy drinkers compared to those who had been categorized as controlled drinkers or abstinent. Abstinent patients reported fewer alcohol-related problems and better psychosocial functioning than heavy drinkers. Women achieved higher abstinence rates (47.2% versus 29.0%, P = 0.005) and had lower mortality (22.4% versus 34.5%, P = 0.03) than men. CONCLUSIONS Over the long-term, abstinence is the most frequent and stable drinking outcome achieved and is associated with fewer problems and better psychosocial functioning. Controlled drinking is rarely achieved and sustained. Women appear to do better than men in the long term.
Cytotoxic triterpenoids and steroids from the bark of Melia azedarach.

Two new triterpenoids (1, 2) and two new steroids (3, 4) along with twelve related known compounds (5-16) were isolated from the bark of Melia azedarach. The new structures were elucidated by means of spectroscopic methods and molecular modeling studies and found to be 21,24-cycloeupha-7-ene-3 β,16 β,21 α,25-tetrol (1), 3 β-acetoxy-12 β-hydroxy-eupha-7,24-dien-21,16 β-olide (2), 29-hydroperoxy-stigmasta-7,24(28) E-dien-3 β-ol (3), and 24 ξ-hydroperoxy-24-vinyl-lathosterol (4). All isolated compounds were tested for their cytotoxic activity against three human cancer cell lines (A549, H460, HGC27) using the CellTiter Glo™ luminescent cell viability assay. Among them, compounds 2- 4, 24 ξ-hydroperoxy-24-vinyl-cholesterol (6), kulinone (7), meliastatin 3 ( 8), 3-oxo-olean-12-en-28-oic acid (10), and (22 E,24 S)-5 α,8 α-epidioxy-24-methyl-cholesta-6,22-dien-3 β-ol (12) were found to have cytotoxic effects, with IC₅₀ values of 5.6-21.2 µg/mL.
The time course of endogenous erythropoietin, IL‐6, and TNFα in response to acute hypoxic exposures

Erythropoietin (EPO) rapidly decreases on return to sea level (SL) after chronic altitude exposure. Acute hypoxia may provide an additional stimulus to prevent the decline in EPO. Proinflammatory cytokines, interleukin‐6 (IL‐6), and tumor necrosis factor alpha (TNFα) have been shown to inhibit EPO production. Optimal normobaric hypoxic exposure has not been established; therefore, investigation of methods eliciting the greatest response in EPO to limit physiological stress is required. Eight men (age 27 ± 4 years, body mass 77.5 ± 9.0 kg, height 179 ± 6 cm) performed four passive exposures to different normobaric hypoxic severities [FiO2: 0.209 (SL), FiO2: ~0.135 (3600 m), FiO2: ~0.125 (4200 m) and FiO2: ~0.115 (4800 m)] in a hypoxic chamber for 2 h. Venous blood was drawn pre‐exposure and then at 1, 2, 4, 6, and 8 h to determine EPO concentration ([EPO]), IL‐6, and TNFα. During 4200 and 4800 m, [EPO] increased from 5.9 ± 1.5 to 8.1 ± 1.5 mU/mL (P = 0.009) and 6.0 ± 1.4 to 8.9 ± 2.0 mU/mL (P = 0.037), respectively, with [EPO] increase peaking at 4 h (2 h post‐exposure). There were no differences in IL‐6 or TNFα during or post‐exposure. Increased [EPO] was found 2 h post hypoxic exposure as result of 2 h of normobaric hypoxia ≥4200 m. There was no dose–response relationship in [EPO] between simulated hypoxia severities.
Field dependence study of in vivo brain 31P MRS up to 16.4 T

In vivo 31P MRS provides a unique tool for studying bioenergetics of living organs. Although its utility has been limited by the relatively low 31P NMR sensitivity, increasing magnetic field strength (B0) could significantly improve the quality and reliability of the 31P MR spectra for biomedical research. To quantitatively understand the field dependence of in vivo 31P MRS for brain applications, 31P NMR sensitivity of phosphocreatine (PCr) in rat brains was measured and compared at 9.4 T and 16.4 T. Additionally, the linewidths and T1 relaxation times of PCr and adenosine triphosphate (ATP) resonances obtained from human and animal brains over a wide B0 range from 4 T, 7 T, and 9.4 T to 16.4 T were examined and their field dependences were quantified. The results indicate an approximate 1.74‐fold 31P signal‐to‐noise ratio (SNR) gain for PCr at 16.4 T compared with 9.4 T. An approximate power 1.4 dependence of 31P SNR on B0 was concluded. Substantial improvements in spectral resolution and significantly shortened T1 values of brain PCr and ATP were observed at high/ultrahigh fields, contributing to an additional sensitivity gain and spectral improvement. In summary, the overall findings from this study suggest that in vivo 31P MRS should greatly benefit from high/ultrahigh fields for noninvasive assessment of altered bioenergetics and metabolic processes associated with brain function and neurological diseases. Copyright © 2014 John Wiley & Sons, Ltd.
Imitation of alcohol consumption in same-sex and other-sex dyads.

AIM Being exposed to other people's drinking behavior has been demonstrated to influence individual's drinking levels. Imitation of alcohol consumption has mainly been investigated among same-sex drinking partners. This study examined whether imitation of alcohol consumption differs when people drink with same-sex or other-sex partners. METHOD To test the imitation effects, a two (drinking condition: alcohol versus no alcohol) by two (sex constellation of dyad: same-sex versus other-sex) mixed between-within subject design was used. In two separate sessions situated in a naturalistic drinking setting (i.e., a bar laboratory), 66 participants were exposed to a same-sex and an other-sex model (i.e., a confederate) who consumed either alcoholic or non-alcoholic beverages. We expected that men would imitate more when drinking with women and men, and that women would imitate less when drinking with men. RESULTS Imitation of alcohol consumption did not differ when participants were drinking with same-sex partners compared with other-sex partners. No gender differences in imitation were found. CONCLUSION Imitation of alcohol consumption can be generalized to situations in which people drink with other-sex partners. Men and women seem to imitate regardless of their drinking partner's sex.
Pulmonary valve preservation and restoration strategies for repair of tetralogy of Fallot*

Abstract Despite tremendous advances in surgical treatment of tetralogy of Fallot, augmenting the small right ventricular outflow tract remains a challenge. Transannular patch augmentation revolutionised surgical management, but did so at the expense of rendering patients with pulmonary insufficiency and the resulting problems associated therewith. Recent surgical efforts have focused on pulmonary valve preservation at initial correction and pulmonary valve restoration after transannular patching, with favourable results. In this manuscript, we review methods of pulmonary valve preservation and restoration.
Teenage meal patterns and food choices in a Finnish city

The aim of this study was to identify meal patterns among Finnish teenagers and factors influencing them, and the role of teenagers’ independent food choices in their weekday eating schedules. A semistructured interview was carried out on 35 14‐year‐old teenagers selected from a school in the center of Helsinki, the capital. Additional information was obtained by questionnaire and observations. The majority of subjects followed a three‐meal pattern of breakfast, lunch and dinner. In blue‐collar families mothers took care of meal preparation, teenagers had fewer outside activities and ate three meals a day. White‐collar family meal patterns were more irregular with mothers working late and children with outside interests at dinner time. Finnish urban middle‐class life style does not support regular family meals. Most teenagers bought candies during the lunch hour. Those who did not lacked close classmates. Milk and sandwiches were eaten at home after school; hamburgers were consumed outside a couple of tim.
Insulin glulisine has a faster onset of action compared with insulin aspart in healthy volunteers.

AIM Because of its zinc-free formulation insulin glulisine (GLU) might have a faster onset of action than other short-acting analogues. We compared the pharmacokinetics and pharmacodynamics of GLU with those of insulin aspart (ASP). METHODS Twelve healthy subjects, aged 18-65 years, participated in this randomized, double-blind, crossover trial. Subjects received 0.2 U/kg GLU or ASP under euglycaemic glucose-clamp conditions. RESULTS GLU showed a significantly higher early metabolic effect (area under the glucose infusion rate (GIR) curve in the first 30 min AUC-GIR (0-)30↓ min 30.3 ± 26.4 vs. 16.2 ± 18.4 mg/kg, P = 0.0421) than ASP, an earlier onset of action (time to 10% of GIR (max) (GIR (max)-t (10%)) 9 vs. 17 min, P = 0.0146) and a faster absorption (shorter times to 10% and 20% of INS (max,) P = 0.0005 each). CONCLUSIONS As demonstrated previously versus lispro, GLU, the only analogue formulated without zinc, also has an earlier onset of action than ASP.
Characterization of the peak at 2.06 ppm in 31P magnetic resonance spectroscopy of human liver: phosphoenolpyruvate or phosphatidylcholine?

High field MR scanners can resolve a metabolite resonating at 2.06 ppm in the in vivo proton‐decoupled liver 31P MR spectrum. Traditionally this peak has been assigned to phosphoenolpyruvate (PEP), the key metabolite for gluconeogenesis. However, recent evidence supported the assignment to biliary phosphatidylcholine (PtdCh), which is produced in the liver and stored in the gall bladder.
Compartment Syndromes

Compartment syndrome can be defined as increased tissue pressure within a closed myofascial space, resulting in disturbed microcirculation and the potential for irreversible neuromuscular ischemic damage. It may present either acutely or chronically. Acute compartment syndrome most commonly occurs following lower limb trauma, and emergency decompression through open and extensive fasciotomies is the treatment of choice. There is little place for imaging in the acute setting because the diagnosis should be made on clinical grounds, possibly supported by measurements of compartmental pressure. Chronic compartment syndrome is more common, usually presenting with recurrent episodes of pain on exercise. The demonstration of elevated compartment pressures following exercise is currently the gold standard method for diagnosis. There is increasing interest in the use of imaging as either a potential alternative to compartmental pressure measurement or as an initial screening investigation prior to invasive testing. The literature evaluating the use of imaging techniques is reviewed, with an emphasis on the potential role of postexertional magnetic resonance imaging.
Gastrointestinal Cancer : Targets and Therapy Neoplastic lesions of endocrine cells in the gastrointestinal tract : ten evolving principles as a basis for clinical understanding

Correspondence: Ben Lawrence Gastrointestinal Pathobiology Research Group, Department of Surgery, Yale University School of Medicine, 310 Cedar Street, PO Box 208602, New Haven, CT 06520-8062, USA Email b.lawrence@auckland.ac. nz Abstract: Timely and appropriate diagnosis and treatment of patients with gastroenteropancreatic neuroendocrine neoplasms is a difficult clinical endeavor. The field is particularly dynamic, not only in terms of expanding therapeutic options, but in the classifications and biological principles that underpin good decision-making. Acknowledging the confusion created by past changes and the inevitability of future development, we combine our clinical experience with a review of the literature to frame the current understanding of gastroenteropancreatic neuroendocrine neoplasms in terms of a set of principles that have stabilized in the midst of this change. Firstly, we present five principles that guide classification of neuroendocrine neoplasms; specifically principles of prognostic classification, mechanisms of tumorigenesis, undiagnosed disease burden, clues regarding genetic etiology, and typical clinical presentation. Secondly, we offer five clinical principles upon which to build a therapeutic strategy. Specifically, these treatment principles include the separation of options by tumor cell differentiation, and the site of the primary lesion in well differentiated tumors. Chromogranin A is a moderately useful biomarker. Treatment should only be considered by clinicians in a multidisciplinary team, and in the face of multiple potential therapeutic options without a supporting evidence base, clinical trial enrolment remains imperative. Therefore, we provide a current synopsis of classification of gastroenteropancreatic neuroendocrine neoplasms, and their etiology, clinical presentation, and management in a novel framework of ten relatively stable principles.
Reproducibility and optimization of in  vivo human diffusion‐weighted MRS of the corpus callosum at 3T and 7T

Diffusion‐weighted MRS (DWS) of brain metabolites enables the study of cell‐specific alterations in tissue microstructure by probing the diffusion of intracellular metabolites. In particular, the diffusion properties of neuronal N‐acetylaspartate (NAA), typically co‐measured with N‐acetylaspartyl glutamate (NAAG) (NAA + NAAG = tNAA), have been shown to be sensitive to intraneuronal/axonal damage in pathologies such as stroke and multiple sclerosis. Lacking, so far, are empirical assessments of the reproducibility of DWS measures across time and subjects, as well as a systematic investigation of the optimal acquisition parameters for DWS experiments, both of which are sorely needed for clinical applications of the method. In this study, we acquired comprehensive single‐volume DWS datasets of the human corpus callosum at 3T and 7T. We investigated the inter‐ and intra‐subject variability of empirical and modeled diffusion properties of tNAA [Davg(tNAA) and Dmodel(tNAA), respectively]. Subsequently, we used a jackknife‐like resampling approach to explore the variance of these properties in partial data subsets reflecting different total scan durations. The coefficients of variation (CV) and repeatability coefficients (CR) for Davg(tNAA) and Dmodel(tNAA) were calculated for both 3T and 7T, with overall lower variability in the 7T results. Although this work is limited to the estimation of the diffusion properties in the corpus callosum, we show that a careful choice of diffusion‐weighting conditions at both field strengths allows the accurate measurement of tNAA diffusion properties in clinically relevant experimental time. Based on the resampling results, we suggest optimized acquisition schemes of 13‐min duration at 3T and 10‐min duration at 7T, whilst retaining low variability (CV ≈ 8%) for the tNAA diffusion measures. Power calculations for the estimation of Dmodel(tNAA) and Davg(tNAA) based on the suggested schemes show that less than 21 subjects per group are sufficient for the detection of a 10% effect between two groups in case–control studies. Copyright © 2015 John Wiley & Sons, Ltd.
Ultimate Confinement of Phonon Propagation in Silicon Nanocrystalline Structure.

Temperature-dependent thermal conductivity of epitaxial silicon nanocrystalline (SiNC) structures composed of nanometer-sized grains separated by ultrathin silicon-oxide (SiO_{2}) films (∼0.3 nm) is measured by the time domain thermoreflectance technique in the range from 50 to 300 K. The thermal conductivity of SiNC structures with a grain size of 3 and 5 nm is anomalously low at the entire temperature range, significantly below the values of bulk amorphous Si and SiO_{2}. The phonon gas kinetic model, with intrinsic transport properties obtained by first-principles-based anharmonic lattice dynamics and phonon transmittance across ultrathin SiO_{2} films obtained by atomistic Green's function, reproduces the measured thermal conductivity without any fitting parameters. The analysis reveals that mean free paths of acoustic phonons in the SiNC structures are equivalent or even below half the phonon wavelength, i.e., the minimum thermal conductivity scenario. The result demonstrates that the nanostructures with extremely small length scales and a controlled interface can give rise to ultimate classical confinement of thermal phonon propagation.