Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of temperature on slow and fast inactivation of rat skeletal muscle Na+channels.

Patch-clamp studies of mammalian skeletal muscle Na+ channels are commonly done at subphysiological temperatures, usually room temperature. However, at subphysiological temperatures, most Na+ channels are inactivated at the cell resting potential. This study examined the effects of temperature on fast and slow inactivation of Na+ channels to determine if temperature changed the fraction of Na+ channels that were excitable at resting potential. The loose patch voltage clamp recorded Na+ currents ( I Na) in vitro at 19, 25, 31, and 37°C from the sarcolemma of rat type IIb fast-twitch omohyoid skeletal muscle fibers. Temperature affected the fraction of Na+ channels that were excitable at the resting potential. At 19°C, only 30% of channels were excitable at the resting potential. In contrast, at 37°C, 93% of Na+ channels were excitable at the resting potential. Temperature did not alter the resting potential or the voltage dependencies of activation or fast inactivation. I Na available at the resting potential increased with temperature because the steady-state voltage dependence of slow inactivation shifted in a depolarizing direction with increasing temperature. The membrane potential at which half of the Na+channels were in the slow inactivated state was shifted by +16 mV at 37°C compared with 19°C. Consequently, the low availability of excitable Na+ channels at subphysiological temperatures resulted from channels being in the slow, inactivated state at the resting potential.
Cardiopulmonary baroreceptor control of muscle sympathetic nerve activity in heat-stressed humans.

Whole body heating decreases central venous pressure (CVP) while increasing muscle sympathetic nerve activity (MSNA). In normothermia, similar decreases in CVP elevate MSNA, presumably via cardiopulmonary baroreceptor unloading. The purpose of this project was to identify whether increases in MSNA during whole body heating could be attributed to cardiopulmonary baroreceptor unloading coincident with the thermal challenge. Seven subjects were exposed to whole body heating while sublingual temperature, skin blood flow, heart rate, arterial blood pressure, and MSNA were monitored. During the heat stress, 15 ml/kg warmed saline was infused intravenously over 7-10 min to increase CVP and load the cardiopulmonary baroreceptors. We reported previously that this amount of saline was sufficient to return CVP to pre-heat stress levels. Whole body heating increased MSNA from 25 +/- 3 to 39 +/- 3 bursts/min (P < 0. 05). Central blood volume expansion via rapid saline infusion did not significantly decrease MSNA (44 +/- 4 bursts/min, P > 0.05 relative to heat stress period) and did not alter mean arterial blood pressure (MAP) or pulse pressure. To identify whether arterial baroreceptor loading decreases MSNA during heat stress, in a separate protocol MAP was elevated via steady-state infusion of phenylephrine during whole body heating. Increasing MAP from 82 +/- 3 to 93 +/- 4 mmHg (P < 0.05) caused MSNA to decrease from 36 +/- 3 to 15 +/- 4 bursts/min (P < 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating is not the primary mechanism resulting in elevations in MSNA. Moreover, arterial baroreceptors remain capable of modulating MSNA during heat stress.
Sleep apps: what role do they play in clinical medicine?

Purpose of review Today's smartphones boast more computing power than the Apollo Guidance Computer. Given the ubiquity and popularity of smartphones, are we already carrying around miniaturized sleep labs in our pockets? Recent findings There is still a lack of validation studies for consumer sleep technologies in general and apps for monitoring sleep in particular. To overcome this gap, multidisciplinary teams are needed that focus on feasibility work at the intersection of software engineering, data science and clinical sleep medicine. Summary To date, no smartphone app for monitoring sleep through movement sensors has been successfully validated against polysomnography, despite the role and validity of actigraphy in sleep medicine having been well established. Missing separation of concerns, not methodology, poses the key limiting factor: The two essential steps in the monitoring process, data collection and scoring, are chained together inside a black box due to the closed nature of consumer devices. This leaves researchers with little room for influence nor can they access raw data. Multidisciplinary teams that wield complete power over the sleep monitoring process are sorely needed.
Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies.

BACKGROUND Inconsistent findings from observational studies have prolonged the controversy over the effects of dietary glycemic index (GI) and glycemic load (GL) on the risk of certain chronic diseases. OBJECTIVE The objective was to evaluate the association between GI, GL, and chronic disease risk with the use of meta-analysis techniques. DESIGN A systematic review of published reports identified a total of 37 prospective cohort studies of GI and GL and chronic disease risk. Studies were stratified further according to the validity of the tools used to assess dietary intake. Rate ratios (RRs) were estimated in a Cox proportional hazards model and combined by using a random-effects model. RESULTS From 4 to 20 y of follow-up across studies, a total of 40 129 incident cases were identified. For the comparison between the highest and lowest quantiles of GI and GL, significant positive associations were found in fully adjusted models of validated studies for type 2 diabetes (GI RR = 1.40, 95% CI: 1.23, 1.59; GL RR = 1.27, 95% CI: 1.12, 1.45), coronary heart disease (GI RR = 1.25, 95% CI: 1.00, 1.56), gallbladder disease (GI RR = 1.26, 95% CI: 1.13, 1.40; GL RR = 1.41, 95% CI: 1.25, 1.60), breast cancer (GI RR = 1.08, 95% CI: 1.02, 1.16), and all diseases combined (GI RR = 1.14, 95% CI: 1.09, 1.19; GL RR = 1.09, 95% CI: 1.04, 1.15). CONCLUSIONS Low-GI and/or low-GL diets are independently associated with a reduced risk of certain chronic diseases. In diabetes and heart disease, the protection is comparable with that seen for whole grain and high fiber intakes. The findings support the hypothesis that higher postprandial glycemia is a universal mechanism for disease progression.
The gut takes nearly all: threonine kinetics in infants.

BACKGROUND Threonine is an essential amino acid that is abundantly present in intestinally produced glycoproteins. Animal studies show that intestinal first-pass threonine metabolism is high, particularly during a restricted enteral protein intake. OBJECTIVE The objective of the study was to quantify intestinal first-pass threonine metabolism in preterm infants during full enteral feeding and during restricted enteral intake. DESIGN Eight preterm infants (x +/- SD birth weight: 1.1 +/- 0.1 kg; gestational age: 29 +/- 2 wk) were studied during 2 periods. During period A, 40% of total intake was administered enterally and 60% was administered parenterally. Total threonine intake was 58 +/- 6 micromol kg(-1) h(-1). During period B, the infants received full enteral feeding, and the total threonine intake was 63 +/- 6 micromol kg(-1) h(-1). Dual stable-isotope tracer techniques were used to assess splanchnic and whole-body threonine kinetics. RESULTS The fractional first-pass threonine uptake by the intestine was remarkably high in both periods: 82 +/- 6% during partial enteral feeding and 70 +/- 6% during full enteral feeding. Net threonine retention was not affected by the route of feeding. CONCLUSION In preterm infants, the splanchnic tissues extract a very large amount of the dietary threonine intake, which indicates a high obligatory visceral need for threonine, presumably for the purposes of synthesis.
Neighborhood socioeconomic status and fruit and vegetable intake among whites, blacks, and Mexican Americans in the United States.

BACKGROUND Socioeconomic and racial-ethnic disparities in health status across the United States are large and persistent. Obesity rates are rising faster in black and Hispanic populations than in white populations, and they foreshadow even greater disparities in chronic illnesses such as diabetes and cardiovascular disease in years to come. Factors that influence dietary intake of fruit and vegetables in these populations are only partly understood. OBJECTIVES We examined associations between fruit and vegetable intake and neighborhood socioeconomic status (SES), analyzed whether neighborhood SES explains racial differences in intake, and explored the extent to which neighborhood SES has differential effects by race-ethnicity of US adults. DESIGN Using geocoded residential addresses from the Third National Health and Nutrition Examination Survey, we merged individual-level data with county and census tract-level US Census data. We estimated 3-level hierarchical models predicting fruit and vegetable intake with individual characteristics and an index of neighborhood SES as explanatory variables. RESULTS Neighborhood SES was positively associated with fruit and vegetable intake: a 1-SD increase in the neighborhood SES index was associated with consumption of nearly 2 additional servings of fruit and vegetables per week. Neighborhood SES explained some of the black-white disparity in fruit and vegetable intake and was differentially associated with fruit and vegetable intake among whites, blacks, and Mexican Americans. CONCLUSIONS The positive association of neighborhood SES with fruit and vegetable intake is one important pathway through which the social environment of neighborhoods affects population health and nutrition for whites, blacks, and Hispanics in the United States.
AKT2 is the predominant AKT isoform expressed in human skeletal muscle

Skeletal muscle physiology and metabolism are regulated by complex networks of intracellular signaling pathways. Among many of these pathways, the protein kinase AKT plays a prominent role. While three AKT isoforms have been identified (AKT1, AKT2, and AKT3), surprisingly little is known regarding isoform‐specific expression of AKT in human skeletal muscle. To address this, we examined the expressions of each AKT isoform in muscle biopsy samples collected from the vastus lateralis of healthy male adults at rest. In muscle, AKT2 was the most highly expressed AKT transcript, exhibiting a 15.4‐fold increase over AKT1 and AKT3 transcripts. Next, the abundance of AKT protein isoforms was determined using antibody immunoprecipitation followed by Liquid Chromatography‐Parallel Reaction Monitoring/Mass Spectrometry. Immunoprecipitation was performed using either mouse or rabbit pan AKT antibodies that were immunoreactive with all three AKT isoforms. We found that AKT2 was the most abundant AKT isoform in human skeletal muscle (4.2‐fold greater than AKT1 using the rabbit antibody and 1.6‐fold greater than AKT1 using the mouse antibody). AKT3 was virtually undetectable. Next, cultured primary human myoblasts were virally‐transduced with cDNAs encoding either wild‐type (WT) or kinase‐inactive AKT1 (AKT1‐K179M) or AKT2 (AKT2‐K181M) and allowed to terminally differentiate. Myotubes expressing WT‐AKT1 or WT‐AKT2 showed enhanced fusion compared to control myotubes, while myotubes expressing AKT1‐K179M showed a 14% reduction in fusion. Myotubes expressing AKT2‐K181M displayed 63% decreased fusion compared to control. Together, these data identify AKT2 as the most highly‐expressed AKT isoform in human skeletal muscle and as the principal AKT isoform regulating human myoblast differentiation.
Prevalence and Risk of Severe Cognitive Impairment in Advanced Chronic Kidney Disease

Background Our primary goal is to describe the prevalence, severity, and risk of cognitive impairment (CI) by estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) in a cohort enriched for advanced chronic kidney disease (CKD; eGFR < 45), adjusting for albuminuria, as measured by urine albumin-to-creatinine ratio (UACR, in mg/g). As both eGFR and albuminuria are associated with CI risk in CKD, we also seek to determine the extent that eGFR remains a useful biomarker for risk of CI in those with CKD and concomitant albuminuria. Methods Chi-square tests measured the prevalence of severe CI and mild cognitive impairment (MCI) by eGFR level. Logistic regression models and generalized linear models measured risk of CI by eGFR, adjusted for UACR. Results Participants were 574 adults with a mean age of 69; 433 with CKD (eGFR < 60, nondialysis) and 141 controls (eGFR ≥ 60). Forty-eight percent of participants with CKD had severe CI or MCI. The prevalence of severe CI was highest (25%) in those with eGFR < 30. eGFR < 30 was only associated with severe CI in those without albuminuria (UACR < 30; OR = 3.3; p = .02) and was not associated with MCI in similar models. Conclusions One quarter of those with eGFR < 30 had severe CI. eGFR < 30 was associated with over threefold increased odds of severe CI in those with UACR < 30, but not with UACR > 30, suggesting that eGFR < 30 is a valid biomarker for increased risk of severe CI in those without concomitant albuminuria.
A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects.

BACKGROUND Angiotensin-converting enzyme (ACE; EC 3.4.15.1) plays a dual role in the regulation of hypertension: it catalyzes the production of the vasoconstrictor angiotensin II and it inactivates the vasodilator bradykinin. By inhibiting these processes, ACE inhibitors have antihypertensive effects. Peptides derived from milk proteins can have ACE-inhibiting properties and may thus be used as antihypertensive components. OBJECTIVE We evaluated the long-term blood pressure-lowering effect of milk fermented by Lactobacillus helveticus LBK-16H in hypertensive subjects. DESIGN In a randomized placebo-controlled study, 39 hypertensive patients received 150 mL/d of either L. helveticus LBK-16H fermented milk or a control product for 21 wk after a 2-wk run-in period. During the run-in period, the average baseline diastolic and systolic blood pressure values were 155 and 97 mm Hg, respectively, in the test product group and 152 and 96 mm Hg, respectively, in the control group. After the run-in period, blood pressure was measured at home on the same day every week with the use of an automatic blood pressure recorder. RESULTS There was a mean difference of 6.7 +/- 3.0 mm Hg in systolic blood pressure (P = 0.030) and of 3.6 +/- 1.9 mm Hg (P = 0.059) in diastolic blood pressure between the test product and control groups. Demographic factors had no significant effect on the responses. CONCLUSION L. helveticus LBK-16H fermented milk containing bioactive peptides in normal daily use has a blood pressure-lowering effect in hypertensive subjects.
Calcium transients in single fibers of low-frequency stimulated fast-twitch muscle of rat.

Ca2+transients were investigated in single fibers isolated from rat extensor digitorum longus muscles exposed to chronic low-frequency stimulation for different time periods up to 10 days. Approximately 2.5-fold increases in resting Ca2+ concentration ([Ca2+]) were observed 2 h after stimulation onset and persisted throughout the stimulation period. The elevated [Ca2+] levels were in the range characteristic of slow-twitch fibers from soleus muscle. In addition, we noticed a transitory elevation of the integral [Ca2+] per pulse with a maximum (∼5-fold) after 1 day. Steep decreases in rate constant of [Ca2+] decay could be explained by an immediate impairment of Ca2+ uptake and, with longer stimulation periods, by an additional loss of cytosolic Ca2+ binding capacity resulting from a decay in parvalbumin content. A partial recovery of the rate constant of [Ca2+] decay in 10-day stimulated muscle could be explained by an increasing mitochondrial contribution to Ca2+ sequestration.
“Hybrid Topics” -- Facilitating the Interpretation of Topics Through the Addition of MeSH Descriptors to Bags of Words

Extracting and understanding information, themes and relationships from large collections of documents is an important task for biomedical researchers. Latent Dirichlet Allocation is an unsupervised topic modeling technique using the bag-of-words assumption that has been applied extensively to unveil hidden thematic information within large sets of documents. In this paper, we added MeSH descriptors to the bag-of-words assumption to generate ‘hybrid topics’, which are mixed vectors of words and descriptors. We evaluated this approach on the quality and interpretability of topics in both a general corpus and a specialized corpus. Our results demonstrated that the coherence of ‘hybrid topics’ is higher than that of regular bag-of-words topics in the specialized corpus. We also found that the proportion of topics that are not associated with MeSH descriptors is higher in the specialized corpus than in the general corpus.
Renal medullary interstitial infusion ofl-arginine prevents hypertension in Dahl salt-sensitive rats.

Studies were designed to examine the effects of renal medullary interstitial infusion of l-arginine (l-Arg) on the development of high-salt-induced hypertension in Dahl salt-sensitive/Rapp (DS) rats. The threshold dose of l-Arg (300 μg ⋅ kg-1 ⋅ min-1) that increased the renal medullary blood flow without altering the cortical blood flow was first determined in anesthetized DS rats. Studies were then carried out to determine the effects of this dose ofl-Arg on salt-induced hypertension in DS rats. In the absence of chronic medullaryl-Arg infusion, mean arterial pressure (MAP) increased in DS rats from 125 ± 2 to 167 ± 5 mmHg by day 5 of a high-salt diet (4.0%), with no change observed in Wistar-Kyoto (WKY) or Dahl salt-resistant/Rapp (DR) rats. MAP did not change significantly with medullary infusion ofl-Arg alone in DR rats (control = 104 ± 1 mmHg) or in WKY rats (control = 120 ± 3 mmHg) and was not significantly changed from these levels during the 7 days ofl-Arg infusion combined with high-NaCl diet. The same amount of l-Arg that prevented salt-induced hypertension in DS rats when infused into the renal medulla (300 μg ⋅ kg-1 ⋅ min-1) failed to blunt salt-induced hypertension when administered intravenously to DS rats. DS rats receiving l-Arg (300 μg ⋅ kg-1 ⋅ min-1iv) exhibited an increase in plasma l-Arg from control concentrations of 138 ± 11 to 218 ± 4 μmol/l, while MAP, which averaged 124 ± 3 mmHg during the 3-day control period, rose to 165 ± 5 mmHg by day 5of high salt (4%) intake. These results indicate that the prevention of salt sensitivity in DS rats was due specifically to the action of l-Arg on renal medullary function and that DS rats may have a deficit of medullary substrate availability and NO production.
Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects.

BACKGROUND Whey proteins have insulinotropic effects and reduce the postprandial glycemia in healthy subjects. The mechanism is not known, but insulinogenic amino acids and the incretin hormones seem to be involved. OBJECTIVE The aim was to evaluate whether supplementation of meals with a high glycemic index (GI) with whey proteins may increase insulin secretion and improve blood glucose control in type 2 diabetic subjects. DESIGN Fourteen diet-treated subjects with type 2 diabetes were served a high-GI breakfast (white bread) and subsequent high-GI lunch (mashed potatoes with meatballs). The breakfast and lunch meals were supplemented with whey on one day; whey was exchanged for lean ham and lactose on another day. Venous blood samples were drawn before and during 4 h after breakfast and 3 h after lunch for the measurement of blood glucose, serum insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1). RESULTS The insulin responses were higher after both breakfast (31%) and lunch (57%) when whey was included in the meal than when whey was not included. After lunch, the blood glucose response was significantly reduced [-21%; 120 min area under the curve (AUC)] after whey ingestion. Postprandial GIP responses were higher after whey ingestion, whereas no differences were found in GLP-1 between the reference and test meals. CONCLUSIONS It can be concluded that the addition of whey to meals with rapidly digested and absorbed carbohydrates stimulates insulin release and reduces postprandial blood glucose excursion after a lunch meal consisting of mashed potatoes and meatballs in type 2 diabetic subjects.
Constitutive and regulative specifications of commitment protocols: A decoupled approach

Interaction protocols play a fundamental role in multiagent systems. In this work, after analyzing the trends that are emerging not only from research on multiagent interaction protocols but also from neighboring fields, like research on workflows and business processes, we propose a novel definition of commitment-based interaction protocols, that is characterized by the decoupling of the constitutive and the regulative specifications and that explicitly foresees a representation of the latter based on constraints among commitments. A clear distinction between the two representations has many advantages, mainly residing in a greater openness of multiagent systems, and an easier reuse of protocols and of action definitions. A language, named 2CL, for writing regulative specifications is also given together with a designer-oriented graphical notation.
Soybean isoflavones, genistein and genistin, inhibit rat myoblast proliferation, fusion and myotube protein synthesis.

The isoflavones, genistein and genistin, are cytotoxic in vitro (e.g. , inhibition of cell proliferation), due in part to inhibition of protein tyrosine kinase and DNA topoisomerase activities. Normal cell functions associated with these enzymatic activities could potentially be impaired in animals through ingestion of soybean products. In this study, cultured rat myogenic cells (L8) were used to determine whether genistein or genistin influences myoblast proliferation and fusion, and myotube protein synthesis and degradation. Genistein or genistin was dissolved in dimethylsulfoxide and included in the culture medium at 0, 1, 10 or 100 micromol/L. Myoblast proliferation was measured by methyl-3H-thymidine incorporation over 48 h. Myoblast differentiation was evaluated by the number of nuclei in multinucleated myotubes. Myotube protein synthesis was measured by 2-h 3H-amino acid incorporation into the myosin and total protein pools after acute (2 h) or chronic (24 h) exposure to similar treatments; protein degradation was measured by measuring radioactivity in protein pools following a time course of protein breakdown after myotube proteins were prelabeled with 3H-amino acids. Genistein or genistin strongly inhibited in vitro myoblast proliferation (P < 0.001) and fusion (P < 0.001) in a dose-dependent manner with effective genistein concentration as low as 1 micromol/L. Genistein or genistin inhibited protein accretion in myotubes (P < 0.001). Decreased protein accretion is largely a result of inhibition on cellular (myofibrillar) protein synthesis rate. No adverse effect on protein degradation was observed. Results suggest that if sufficient circulating concentrations are reached in tissues of animals consuming soy products, genistein/genistin can potentially affect normal muscle growth and development.