Miracle-dz/UniFAR-FTUs huggingface dataset:
Moderate‐intensity endurance training improves endothelial glycocalyx layer integrity in healthy young men

What is the central question of this study? The main aim of the present study was to determine the effect of prolonged moderate‐intensity endurance training on the endothelial glycocalyx layer integrity in relationship to the training‐induced changes in oxidative stress and antioxidant defence in humans. What is the main finding and its importance? We have shown, for the first time, a protective effect of prolonged moderate‐intensity endurance training on endothelial glycocalyx layer integrity, as judged by significantly lower basal and end‐exercise serum concentrations of glycocalyx damage markers, i.e. syndecan‐1 and heparan sulfate, accompanied by attenuation of oxidative stress and enhancement of antioxidant defence after training in previously untrained healthy young men.
The influence of sodium bicarbonate on maximal force and rates of force development in the triceps surae and brachii during fatiguing exercise

What is the central question of this study? Does metabolic alkalosis in humans, induced by sodium bicarbonate, affect rates of skeletal muscle fatigue differentially in muscle groups composed predominately of slow‐ and fast‐twitch fibres? What is the main finding and its importance? Sodium bicarbonate exhibited no effect on the fatigue profile observed between triceps surae and brachii muscle groups during and after 2 min of tetanic stimulation. For the first time in exercising humans, we have profiled the effect of sodium bicarbonate on the voluntary and involuntary contractile characteristics of muscle groups representative of predominately slow‐ and fast‐twitch fibres.
Pharmacogenetic Considerations in the Management of HIV Infection

Potent combination antiretroviral drug therapy has now been available to HIV-infected patients for more than a decade, resulting in a significant decline in disease-related morbidity and mortality. Nonetheless, a number of HIV-infected individuals fail to experience the full benefit of their antiretroviral medications; some lack a robust virologic response, while others experience treatment-limiting toxicities. A number of factors may contribute to variable drug response in patients with HIV infection. Virologic, immunologic, pharmacologic, and pharmacokinetic differences between HIV-infected patients have all been noted to contribute to interpatient variability in drug response. Recent data suggest that pharmacogenetic differences among HIV-infected individuals may also be an important variable that contributes to antiretroviral drug response. Pharmacogenetic studies of antiretroviral drug therapy have explored the influence of single nucleotide polymorphisms in genes responsible for key proteins involved in antiretroviral drug metabolism (cytochrome P50 enzymes) and drug transport (P-glycoprotein). In addition, the human leukocyte antigen genotype (HLA-B*57) has been found to predict abacavir-associated hypersensitivity reactions. Antiretroviral pharmacogenetics offers the possibility of optimizing virologic response and minimizing drug toxicity by individualizing anti-HIV pharmacotherapy. The authors review those genetic polymorphisms that have been shown, or are strongly suspected, to influence antiretroviral drug metabolism, transport, and toxicity.
A novel lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a prospective cohort study

Background and study aims: A novel large-diameter, lumen-apposing, self-expanding metal stent with bilateral flanges was recently developed for endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic pancreatic fluid collections (PFCs). The aim of this study was to evaluate the efficacy and safety of this stent in a large cohort. Patients and methods: Patients with a PFC undergoing EUS-guided drainage with this novel stent were prospectively enrolled in this multicenter cohort study. Results: There were 61 patients: 46 patients (75 %) with walled-off necrosis (WON) and 15 (25 %) with a pancreatic pseudocyst. Stent placement was technically successful in 60 patients (98 %, 95 %CI 95 % – 100 %). Clinical success, defined as resolution of clinical symptoms in combination with a decrease in the PFC size to ≤ 2 cm on imaging, was achieved in 93 % of patients with a pancreatic pseudocyst (95 %CI 77 % – 100 %) and in 81 % of patients with WON (95 %CI 69 % – 94 %). Treatment failure occurred in nine patients (16 %, 95 %CI 6 % – 26 %), including four patients who required surgical intervention. Stent removal was performed in 82 % of patients after a median of 32 days (range 2 – 178) and was rated as easy in all but one patient. In 10 patients, endoscopic stent removal was not performed because of stent migration (n = 3), stent dislodgement during necrosectomy (n = 3), stent removal during surgery (n = 2), or refusal by the patient (n = 2). In total, five major complications were reported (9 %, 95 %CI 2 % – 16 %), including PFC infection (n = 4) and perforation (n = 1). Conclusion: EUS-guided drainage using this novel stent is feasible and the clinical results obtained are promising with a low major complication rate.
Proteomic analysis of defense response of wildtype Arabidopsis thaliana and plants with impaired NO‐ homeostasis

In recent years, nitric oxide (NO) has been recognized as a signalling molecule of plants, being involved in diverse processes like germination, root growth, stomatal closing, and responses to various stresses. A mechanism of how NO can regulate physiological processes is the modulation of cysteine residues of proteins (S‐nitrosylation) by S‐nitrosoglutathione (GSNO), a physiological NO donor. The concentration of GSNO and the level of S‐nitrosylated proteins are regulated by GSNO reductase, which seems to play a major role in NO signalling. To investigate the importance of NO in plant defense response, we performed a proteomic analysis of Arabidopsis wildtype and GSNO‐reductase knock‐out plants infected with both the avirulent and virulent pathogen strains of Pseudomonas syringae. Using 2‐D DIGE technology in combination with MS, we identified proteins, which are differentially accumulated during the infection process. We observed that both lines were more resistant to avirulent infections than to virulent infections mainly due to the accumulation of stress‐, redox‐, and defense‐related proteins. Interestingly, after virulent infections, we also observed accumulation of defense‐related proteins, but no or low accumulation of stress‐ and redox‐related proteins, respectively. In summary, we present here the first detailed proteomic analysis of plant defense response.
Do changes in neuromuscular activation contribute to the knee extensor angle–torque relationship?

What is the central question of the study? Do changes in neuromuscular activation contribute to the knee extensor angle–torque relationship? What is the main finding and its importance? Both agonist (quadriceps) and antagonist coactivation (hamstrings) differed with knee joint angle during maximal isometric knee extensions and thus both are likely to contribute to the angle–torque relationship. Specifically, two independent measurement techniques showed quadriceps activation to be lower at more extended positions. These effects might influence the capacity for neural changes in response to training and rehabilitation at different knee joint angles.
Eating Disorders and Disturbance in Children and Adolescents With Cystic Fibrosis

People with cystic fibrosis are considered at risk for developing anorexia (Raymond et al., 2000), but studies have used methodologically flawed measures. Using improved methodology, the current study examines the prevalence of eating disorders/disturbance in adolescents with CF. Method: 55 adolescents with CF, age range 11–17 years (mean 14.2 years) randomly selected were administered the Child Eating Disorder Examination (Bryant-Waugh, Cooper, Taylor, & Lask, 1996). Results: No participant met full criteria for a diagnosis of anorexia or bulimia. Of those with a BMI ≤ 17.5, 5% avoided weight gain. Fifty-three percent demonstrated disturbed eating attitudes and 16% disturbed eating behaviours. Discussion: The study finds that gold standard diagnostic methods indicate the prevalence of disturbed eating attitudes and behaviors in CF.
The dynamic protein partnership of RNA polymerase inBacillus subtilis

In prokaryotes, transcription results from the activity of a 400 kDa RNA polymerase (RNAP) protein complex composed of at least five subunits (2α, β, β′, ω). To ensure adequate responses to changing environmental cues, RNAP activity is tightly controlled by means of interacting regulatory proteins. Here, we report the affinity‐purification of the Bacillus subtilis RNAP complexes from cells in different growth states and stress conditions, and the quantitative assessment by mass spectrometry of the dynamic changes in the composition of the RNAP complex. The stoichiometry of RNA polymerase was determined by a comparison of two mass spectrometry‐based quantification methods: a label‐based and a label‐free method. The validated label‐free method was then used to quantify the proteins associated with RNAP. The levels of sigma factors bound to RNAP varied during growth and exposure to stress. Elongation factors, helicases such as HelD and PcrA, and novel unknown proteins were also associated with RNAP complexes. The content in 6S RNAs of purified RNAP complexes increased at the onset of the stationary phase. These quantitative variations in the protein and RNA composition of the RNAP complexes well correlate with the known physiology of B. subtilis cells under different conditions.
Do male athletes with already high initial haemoglobin mass benefit from ‘live high–train low’ altitude training?

What is the central question of this study? It has been assumed that athletes embarking on an ‘live high–train low’ (LHTL) camp with already high initial haemoglobin mass (Hbmass) have a limited ability to increase their Hbmass further post‐intervention. Therefore, the relationship between initial Hbmass and post‐intervention increase was tested with duplicate Hbmass measures and comparable hypoxic doses in male athletes. What is the main finding and its importance? There were trivial to moderate inverse relationships between initial Hbmass and percentage Hbmass increase in endurance and team‐sport athletes after the LHTL camp, indicating that even athletes with higher initial Hbmass can reasonably expect Hbmass gains post‐LHTL.
Three‐dimensional morphology and volume of the free Achilles tendon at rest and under load in people with unilateral mid‐portion Achilles tendinopathy

What is the central question of this study? The aim was to determine the effect of mid‐portion Achilles tendinopathy (MAT) on free Achilles tendon three‐dimensional morphology and volume at rest and under load in people with unilateral MAT. What is the main finding and its importance? Tendinopathic tendon had a larger resting tendon cross‐sectional area and anteroposterior diameter relative to healthy tendon. When loaded, tendinopathic tendon experienced a reduction in transverse morphology (i.e. cross‐sectional area, anteroposterior and mediolateral diameters) and overall volume reduction. In contrast, the healthy tendon remained isovolumetric and bulged along the anteroposterior axis. These findings suggest a fundamental reorganization of tendinopathic tendon matrix components and altered tendon fluid content when under load.
Evaluation of Adequacy of Reading Level and Readability of Psychotropic Medication Handouts

BACKGROUND: Patient education is an essential element to quality health care, both in the physical health andmental health care arenas. Providers use written materials as tools to educate, but benefits are dependent on learners’ reading and comprehension abilities. OBJECTIVE: The purpose of this descriptive study was to evaluate adequacy of reading level and readability of psychotropic medication patient handouts. STUDYDESIGN: Reading level and readability of 15 psychotropic medication patient handouts were evaluated using the SMOG formula and the Readability Assessment Instrument, respectively. RESULTS: All 15 handouts were written at inadequate reading levels and readability. Reading levels were above 12th grade, with amean of 13.5 (± 1.5 grades), and overall readability was below the acceptable score of 80% (M= 6%). CONCLUSIONS: Inadequate reading skills and comprehension may impede patients’ learning and their ability to understand their illness and follow provider instructions. Providersmust ensure education materials are written at adequate reading and readability levels to optimize learning and maximize desired outcomes related to treatment.
Predictors of Treatment Engagement for Young Children Exposed to Violence

This study examined factors associated with treatment engagement and child outcomes in 1,365 children receiving community-based services for exposure to violence. Data were collected on children and families who completed an intake interview. Children were categorized into groups based on whether they attended any therapy sessions after the intake, terminated prematurely from therapy, or completed treatment. Results demonstrated that child emotional and behavioral problems at intake, general parent stress, and income did not differ by treatment engagement. Type of violence exposure, parent–child stress, and race differed by category of treatment engagement. Strategies from Safe From the Start service providers to increase treatment engagement are included in the discussion.
Angiotensin‐converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor

Angiotensin‐converting enzyme 2 (ACE2) is thought to act in an opposing manner to its homologue, angiotensin‐converting enzyme (ACE), by inactivating the vasoconstrictor peptide angiotensin II and generating the vasodilatory fragment, angiotensin(1–7). Both ACE and ACE2 are membrane‐bound ectoenzymes and may circulate in plasma as a consequence of a proteolytic shedding event. In this study, we show that ACE2 circulates in human plasma, but its activity is suppressed by the presence of an endogenous inhibitor. Partial purification of this inhibitor indicated that the inhibitor is small, hydrophilic and cationic, but not a divalent metal cation. These observations led us to develop a method for removal of the inhibitor, thus allowing detection of plasma ACE2 levels using a sensitive quenched fluorescent substrate‐based assay. Using this technique, ACE2 activity measured in plasma from healthy volunteers (n= 18) ranged from 1.31 to 8.69 pmol substrate cleaved min−1 ml−1 (mean ±s.e.m., 4.44 ± 0.56 pmol min−1 ml−1). Future studies of patients with cardiovascular, renal and liver disease will determine whether plasma ACE2 is elevated in parallel with increased tissue levels observed in these conditions.
Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin‐converting enzyme 2 expression

Patients with kidney failure are at high risk of a cardiac death and frequently develop left ventricular hypertrophy (LVH). The mechanisms involved in the cardiac structural changes that occur in kidney failure are yet to be fully delineated. Angiotensin‐converting enzyme (ACE) 2 is a newly described enzyme that is expressed in the heart and plays an important role in cardiac function. This study assessed whether ACE2 plays a role in the cardiac remodelling that occurs in experimental acute kidney injury (AKI). Sprague–Dawley rats had sham (control) or subtotal nephrectomy surgery (STNx). Control rats received vehicle (n= 10), and STNx rats received the ACE inhibitor (ACEi) ramipril, 1 mg kg−1 day−1 (n= 15) or vehicle (n= 13) orally for 10 days after surgery. Rats with AKI had polyuria (P < 0.001), proteinuria (P < 0.001) and hypertension (P < 0.001). Cardiac structural changes were present and characterized by LVH (P < 0.001), fibrosis (P < 0.001) and increased cardiac brain natriuretic peptide (BNP) mRNA (P < 0.01). These changes occurred in association with a significant increase in cardiac ACE2 gene expression (P < 0.01) and ACE2 activity (P < 0.05). Ramipril decreased blood pressure (P < 0.001), LVH (P < 0.001), fibrosis (P < 0.01) and BNP mRNA (P < 0.01). These changes occurred in association with inhibition of cardiac ACE (P < 0.05) and a reduction in cardiac ACE2 activity (P < 0.01). These data suggest that AKI, even at 10 days, promotes cardiac injury that is characterized by hypertrophy, fibrosis and increased cardiac ACE2. Angiotensin‐converting enzyme 2, by promoting the production of the antifibrotic peptide angiotensin(1–7), may have a cardioprotective role in AKI, particularly since amelioration of adverse cardiac effects with ACE inhibition was associated with normalization of cardiac ACE2 activity.
Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity

Recent studies have demonstrated the presence of the (pro)renin receptor (PRR) in the glomerular mesangium and the subendothelial layer of the renal arteries. We hypothesized that diabetes upregulates PRR expression through enhanced angiotensin subtype 1 (AT1) receptor–NADPH oxidase cascade activity. Using real‐time polymerase chain reaction, Western blot analysis and immunostaining, we studied renal localization of the PRR in the streptozotocin‐induced diabetic rat model and in response to 1 week of treatment with the AT1 receptor blocker valsartan (10 mg kg−1 day−1), the angiotensin AT2 receptor blocker PD123319 (0.5 mg kg−1 day−1) or the NADPH oxidase inhibitor diphenylene iodonium (DPI; 0.5 mg kg−1 day−1) 6 weeks post‐induction of diabetes. Both PRR mRNA and protein were expressed constitutively in the kidneys of normal rat renal cortex and medulla, mainly in glomerular mesangium, proximal, distal and collecting tubules. Compared with normal rats (100%), diabetic rats demonstrated an increase in renal PRR mRNA (184%), protein (228%) and immunostaining. Valsartan and DPI prevented the increase in the PRR mRNA (106 and 126%, respectively), protein (97 and 140%, respectively) and immunostaining that was seen in the kidneys of diabetic rats. The AT2 blocker PD123319 did not have significant effects on PRR mRNA (157%) or protein expression (200%) in the kidneys of diabetic rats. These results demonstrate that the PRR is constitutively expressed in renal glomeruli and tubules. Expression of the PRR is upregulated in diabetes via enhancement of AT1 receptor–NADPH oxidase activity.
Proteome reference map of Lactobacillus acidophilus NCFM and quantitative proteomics towards understanding the prebiotic action of lactitol

Lactobacillus acidophilus NCFM is a probiotic bacterium adapted to survive in the gastrointestinal tract and with potential health benefits to the host. Lactitol is a synthetic sugar alcohol used as a sugar replacement in low calorie foods and selectively stimulating growth of L. acidophilus NCFM. In the present study the whole‐cell extract proteome of L. acidophilus NCFM grown on glucose until late exponential phase was resolved by 2‐DE (pH 3–7). A total of 275 unique proteins assigned to various physiological processes were identified from 650 spots. Differential 2‐DE (DIGE) (pH 4–7) of L. acidophilus NCFM grown on glucose and lactitol, revealed 68 spots with modified relative intensity. Thirty‐two unique proteins were identified in 41 of these spots changing 1.6–12.7‐fold in relative abundance by adaptation of L. acidophilus NCFM to growth on lactitol. These proteins included β‐galactosidase small subunit, galactokinase, galactose‐1‐phosphate uridylyltransferase and UDP‐glucose‐4‐epimerase, which all are potentially involved in lactitol metabolism. This first comprehensive proteome analysis of L. acidophilus NCFM provides insights into protein abundance changes elicited by the prebiotic lactitol.
Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate‐mediated attenuation

Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia‐induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro‐arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min−1), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 ± 9 Ω, from 611 ± 24 Ω, n= 16) when compared with intact control dogs (+43 ± 5 Ω, from 620 ± 20 Ω, n= 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 ± 11 to 193 ± 15 beats min−1) and MEI (+12 ± 1.1 Ω, from 663 ± 18 Ω). In contrast, VNS during ischaemia (n= 11) abruptly reduced HR (from 206 ± 6 to 73 ± 9 beats min−1) and MEI (−16 ± 2 Ω, from 700 ± 44 Ω). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG‐derived indices of ischaemia (e.g. ST segment, 0.22 ± 0.03 versus 0.15 ± 0.03 mV) and of rate‐corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 ± 4.2 versus 65.8 ± 5.9 ms; QTc, 340 ± 8 versus 254 ± 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand.
Altered central catecholaminergic transmission and cardiovascular disease

Numerous studies, some of which date back more than three decades, have established a link between disorders of the cardiovascular system and the catecholaminergic system of the brain. Central noradrenergic (and putative adrenergic) neurones are involved in numerous brain functions, and there appears to be more than one mechanism via which a dysfunction of central nor/adrenergic signalling may be detrimental to the cardiovascular system. Moreover, in some cases, such as essential hypertension, altered noradrenergic transmission could play a causative role. Numerous controversies are evident throughout the literature, which are very difficult to explain without much better understanding of the basic physiology of central noradrenergic transmission. Recently, using a combination of novel molecular, electrochemical and imaging techniques, we have started to unravel how noradrenergic neurones in the brain store and release their transmitter. Targeted long‐term modulation of specific noradrenergic cell groups in defined brain areas using viral gene transfer is helping to clarify the links between central catecholamines and cardiovascular control in health and disease. These studies may reveal new therapeutic strategies for various cardiovascular diseases which are accompanied by heightened sympathetic nerve activity.