Miracle-dz/UniFAR-FTUs huggingface dataset:
Perspective: Ketone Supplementation in Sports-Does It Work?

Oral ketone supplements have gained popularity in recent years. There is biological rationale for a potential ergogenic effect of this type of supplement, as they might not only alter muscle fuel preference during exercise (and promote glycogen sparing, with potential benefits for endurance performance) but also favor cognition performance during exertion or muscle glycogen synthesis after exercise. However, as discussed in this Perspective, evidence to date does not support a benefit of acute ketone supplementation on sports performance, cognition, or muscle recovery [although further research with long-duration exercise (i.e., >60 min), is needed], and the evidence for chronic supplementation is sparse. In addition, acute intake of ketone supplements might be associated with gastrointestinal symptoms, and further research is warranted on the long-term safety of repeated use of ketone supplements. In summary, there is currently insufficient evidence to support the overall effectiveness of ketone supplements in sports.
Association between serum uric acid and spirometric pulmonary function in Korean adults: The 2016 Korea National Health and Nutrition Examination Survey

Background A limited number of epidemiological studies have investigated the association between serum uric acid and pulmonary function in the general population. However, the results have been inconclusive. Objectives This study was performed to investigate the association between serum uric acid and spirometric pulmonary function in general population. Methods Among the 8,150 participants who participated in the 2016 Korea National Health and Nutrition Examination Survey, 2,901 participants were analyzed in this study. Subjects were divided into four groups according to forced vital capacity (FVC)% predicted or forced expiratory volume in 1 second (FEV1) % predicted quartiles. Participants in the lowest quartile of FVC % predicted and FEV1% predicted were compared to those in the remaining quartiles according to age, education level, household income, smoking status, alcohol consumption, aerobic exercise, obesity, hypertension, diabetes, renal impairment, serum uric acid, and hyperuricemia. Multivariable logistic regression analyses were used to calculate the odds ratio (OR) of hyperuricemia for participants in the lowest quartile of FVC% and FEV1 predicted, with above covariates. Results In women, hyperuricemia was associated with lowest quartile of FVC% predicted (OR 1.71, 95% CI 1.06–2.75, p = 0.027) and FEV1 predicted (OR 1.70, 95% CI 1.06–2.74, p = 0.028) respectively, serving as above confounding variables. In men, hyperuricemia (OR 1.54, 95% CI 1.07–2.22, p = 0.021) was associated with the lowest quartile of FEV1% predicted, not FVC% predicted. According to median age, in women, age ≥ 56 years old with hyperuricemia was associated with lowest quartile of FVC% predicted (OR 1.85, 95% CI 1.04–3.28, p = 0.037) and FEV1% predicted (OR 1.99, 95% CI 1.11–3.75, p = 0.021), respectively. In men, age ≥ 56 years old with hyperuricemia was associated with lowest quartile of FEV1% predicted (OR 1.75, 95% CI 1.05–2.94, p = 0.033), not FCV% predicted. Conclusions Hyperuricemia was associated with lowest quartile of FEV1% or FVC% predicted in Korean general population. This correlation between hyperuricemia and low pulmonary function was more pronounced in women and older age.
Outcome after surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures and moderate to severe traumatic brain injury (CWIS-TBI).

Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared to nonoperative management, is associated with favorable outcomes in patients with TBI. METHODS A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were Intensive Care Unit (ICU-LOS) and hospital length of stay (HLOS), tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS 9-12) and severe (GCS ≤8) TBI. RESULTS The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. SSRF was performed at a median of 3 days and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (OR 0.59 (95% CI 0.38-0.98), p=0.043) and 30-day mortality (OR 0.32 (95% CI 0.11-0.91), p=0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (0.19 (95% CI 0.04-0.88), p=0.034). CONCLUSIONS In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI. LEVEL OF EVIDENCE Therapeutic, level IV.
Discovery of novel pyrazole derivatives as a potent anti‐inflammatory agent in RAW264.7 cells via inhibition of NF‐ĸB for possible benefit against SARS‐CoV‐2

Due to unavailability of a specific drug/vaccine to attenuate severe acute respiratory syndrome coronavirus 2, the current strategy to combat the infection has been largely dependent upon the use of anti‐inflammatory drugs to control cytokines storm responsible for respiratory depression. Thus, in this study, we discovered novel pyrazole analogs as a potent nuclear factor kappa B (NF‐ĸB) inhibitor. The compounds were assessed for NF‐ĸB transcriptional inhibitory activity in RAW264.7 cells after stimulation with lipopolysaccharides (LPS), revealing Compound 6c as the most potent analog among the tested series. The effect of Compound 6c was further investigated on the levels of interleukin‐1β, tumor necrosis factor‐α, and interleukin‐6 in LPS‐stimulated RAW267.4 cells by enzyme immunoassay, where it causes a significant reduction in the level of these cytokines. In Western blot analysis, Compound 6c also causes the inhibition of inhibitor kappa B‐α and NF‐κB. It was found to be snugly fitted into the inner grove of the active site of NF‐ĸB by forming H‐bonds and a nonbonded interaction with Asn28 in a docking analysis.
Prevalence of analgesic use in patients with chronic pain referred to a multidisciplinary pain centre and its correlation with patient-reported outcome measures: A cross-sectional, registry-based study.

BACKGROUND Chronic pain is prevalent in Sweden, nearing 20% in the adult population. Treatment often requires a multimodal approach, with medication, physical therapy and psychological interventions. However, the frequency of medication in patients with chronic pain in Sweden, and its correlation with patient-reported outcome measures (PROMs), are currently unknown. OBJECTIVES To investigate the frequency of use of analgesics and other medication in patients with chronic pain referred to a multidisciplinary pain centre, and how opioid treatment relates to PROMs. DESIGN Cross-sectional, registry-based study. PATIENTS New referral visits to the Pain and Rehabilitation Center in Linköping, Sweden in 2015. METHODS Medication data was matched with PROMs. Univariate analysis was conducted with IBM Statistical Package for the Social Sciences (SPSS; IBM Corporation, Somers, NY, USA) version 24.0, and multivariate analysis with SIMCA-P+ (version 13, Umetrics AB, Umeå, Sweden). RESULTS 30% used opioids daily, and this group differed from other patients on many PROMs, with medium effect sizes for pain severity, interference, health-related quality of life, activity engagement, and satisfaction with social life. Multivariate analysis identified four groups and showed that daily use of opioids was associated with high pain intensity and low physical functioning. CONCLUSION Longitudinal studies are warranted (e.g. on the clinical effect of tapering), as are studies that can better explain the medication variability in patients with complex chronic pain.
Pharmacotherapy options for managing hepatitis B in children

ABSTRACT Introduction To eliminate viral hepatitis by 2030, the World Health Organization (WHO) launched the first global health sector strategy on viral hepatitis, with particular focus given to hepatitis B and C in 2016. To achieve the reduction of mortality in children, it is indispensable to know which children should be treated and how to treat them. Area covered In this article, the authors review the antiviral treatment of children with chronic hepatitis B virus (HBV) infection including antivirals available for children with chronic HBV infection. Expert opinion The approvals of nucleos(t)ide analogues (NAs) and pegylated interferon (PEG-IFN) for children have lowered a hurdle to the initiation of antiviral treatment in children. The international guidelines use nearly the same criteria of antiviral treatment for children with chronic HBV infection, but the WHO guidelines provide a cautious stance on the antiviral treatment of children. Not only PEG-IFN but also NAs with a high genetic barrier to drug resistance should be the first-line treatment for children. In settings with limited medical resources, NAs can be the first-line treatment for children. Although the concept of an ‘immune-tolerant phase’ is challenged, evidence is not sufficient to recommend the treatment of HBeAg-positive immune-tolerant children.
Open channel block of Kv1.4 potassium channels by aripiprazole

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K+ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC50 value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC50 value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC50 value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.
Biomarker enzyme activities and ultrastructure of liver of the grass carp Ctenopharyngodon idella (Valenciennes, 1844) exposed to the organophosphate pesticide chlorpyrifos

The present investigation analysed the toxic effects of the organophosphate pesticide chlorpyrifos (CPF) on activities of biomarker enzymes viz., alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and acid phosphatase (ACP) as well as ultrastructural alterations in hepatocytes of grass carp Ctenopharyngodon idella exposed to sublethal concentrations (1.44 and 2.41 μg l-1) for 15, 30 and 60 days. The enzymes showed marked fluctuations post-pesticide treatment. The altered enzymes activities indicated disturbance in the structure and integrity of cell organelles. Ultrastructural alterations such as formation of crescent shaped nucleus along with condensed chromatin, margination of heterochromatin, severe breakdown and fragmentation of endoplasmic reticulum, deformed mitochondria with loss of cristae were observed in the pesticide exposed fishes. The findings revealed exposure period and concentration dependent response in hepatocytes. Ultrastructural changes could be correlated to corresponding alterations in the activities of marker enzymes. At both the toxicant concentrations, altered activities of AST and ALT as markers of glycolysis and protein metabolism indicated disturbances to the cellular metabolism. The observed changes in the liver enzyme levels could be used as sensitive biomarkers for pesticides contamination in grass carp.
Ten Years of National Seasonal Surveillance for Severe Complications of Influenza in Australian Children.

BACKGROUND Severe complications of influenza in children are uncommon but may result in admission to hospital or an intensive care unit (ICU) and death. METHODS Active prospective surveillance using the Australian Paediatric Surveillance Unit with monthly reporting by pediatricians of national demographic and clinical data on children with <15 years of age hospitalized with severe complications of laboratory-confirmed influenza during ten influenza seasons 2008-2017. RESULTS Of 722 children notified, 613 had laboratory-confirmed influenza and at least one severe complication. Most (60%) were <5 years of age; 10% were <6 months, hence ineligible for vaccination. Almost half of all cases were admitted to ICU and 30 died. Most children were previously healthy: 40.3% had at least one underlying medical condition. Sixty-five different severe complications were reported; pneumonia was the most common, occurring in over half of all cases. Influenza A accounted for 68.6% hospitalizations; however, influenza B was more often associated with acute renal failure (P = 0.014), rhabdomyolysis (P = 0.019), myocarditis (P = 0.015), pericarditis (P = 0.013), and cardiomyopathy (P = 0.035). Children who died were more likely to be older (5-14 years), have underlying medical conditions, be admitted to ICU, and have encephalitis, acute renal failure, or myocarditis. Only 36.1% of all children reported received antiviral medications, and 8.5% were known to be vaccinated for seasonal influenza. CONCLUSIONS Severe influenza complications cause morbidity and mortality in children, which may increase if coinfection with COVID-19 occurs in the 2020 season and beyond. Increased vaccination rates, even in healthy children, early diagnosis and timely antiviral treatment are needed to reduce severe complications and death.
Clearance of intracellular tau protein from neuronal cells via VAMP8-induced secretion.

In Alzheimer's disease (AD), tau - a microtubule-associated protein - becomes hyperphosphorylated, aggregates and accumulates in the somato-dendritic compartment of neurons. In parallel to its intracellular accumulation in AD, tau is also released in the extracellular space, as revealed by its increased presence in cerebrospinal fluid. Consistent with this, recent studies, including ours, have reported that neurons secrete tau, and several therapeutic strategies aim to prevent the intracellular tau accumulation. Previously, we reported that late endosomes were implicated in tau secretion. Here, we explore the possibility of preventing intracellular tau accumulation by increasing tau secretion. Using neuronal models, we investigated whether the overexpression of the vesicle-associated membrane protein 8 (VAMP8), an R-SNARE found on late endosomes, could increase tau secretion. The overexpression of VAMP8 significantly increased tau secretion, decreasing its intracellular levels in the neuroblastoma (N2a) cell line. Increased tau secretion by VAMP8 was also observed in murine hippocampal slices. The intracellular reduction of tau by VAMP8 overexpression correlated to a decrease of acetylated tubulin induced by tau overexpression in N2a cells. VAMP8 staining was preferentially found on late endosomes in N2a cells. Using TIRF microscopy, the fusion of VAMP8-positive vesicles with the plasma membrane was correlated to the depletion of tau in the cytoplasm. Finally, overexpression of VAMP8 reduced the intracellular accumulation of tau mutants linked to frontotemporal dementia with parkinsonism (FTDP) and alpha-synuclein by increasing their secretion. Collectively, the present data indicate that VAMP8 could be used to increase tau and alpha-synuclein clearance to prevent their intracellular accumulation.
Phenotypic Variability and Genetic Diversity of Phragmites australis in Quebec and Kashmir Reveal Contrasting Population Structure

The origin of differences in traits influencing competitive success between invasive and native wild populations of alien species is subject of debate. Herbarium-based information sources from 2005 onwards about nativity and distributional range of Phragmites australis were used to survey putative native populations of the species in Quebec, and chloroplast DNA (cpDNA) PCR-RFLP analyses identified only one native population, whereas the same analyses revealed that the Kashmir populations are invasive. We compared the native population of P. australis in Quebec (QN), ten populations invasive to Quebec (QE), and five populations invasive in Kashmir, India (KE) using morphometric traits. Using nine cpDNA microsatellite loci, we also compared nine KE populations, ten QE populations, and the QN population. Phenotypic variation was observed among and within populations. Only dry mass of flowers varied across regions. Characterization of morphotypes defined three distinct haplotypes. A bimodal distribution of stem diameter (SD), internode length (IL), leaf length (LL), and leaf width (LW) suggests that a major gene may control growth traits or occurrence of co-selection. High genetic differentiation was observed between populations (RST = 0.353) and haplotypes (RST = 0.133 to 0.418), indicating limited gene flow and probable local adaptation. Principal coordinates analysis and the neighbor-joining phylogenetic tree clearly distinguished the three haplotypes. Among-populations phenotypic difference (PST) was lower than overall RST for plant height, SD, and fresh and dry mass of flowers and seeds, whereas PST estimates for LL and LW exceeded among-populations RST, suggesting divergent selection, while local adaptation might have occurred in IL, LL, and flower masses. Genetic drift probably influenced among-populations IL differences.
Acute physical exercise increases PI3K‐p110α protein content in the hypothalamus of obese mice

The anatomy of the hypothalamus includes many nuclei and a complex network of neurocircuits. In this context, some hypothalamic nuclei reside closer to the blood‐brain barrier, allowing communication with the peripheral organs through some molecules, such as leptin. Leptin is considered the main adipokine for energy homeostasis control. Furthermore, leptin signalling in the hypothalamus can communicate with insulin signalling through the activation of phosphoinositide 3‐kinase (PI3k). Previous data suggest that isoforms of PI3k are necessary to mediate insulin action in the hypothalamus. However, obese animals show impairment in the central signalling of these hormones. Thus, in the current study, we evaluated the role of acute exercise in the leptin and insulin pathways in the hypothalamus, as well as in food intake control in obese mice. Although acute physical exercise was not able to modulate leptin signalling, this protocol suppressed the increase in the suppressor of cytokine signalling 3 (SOCS3) protein levels. In addition, acute exercise increased the content of PI3k‐p110α protein in the hypothalamus. The exercised animals showed a strong tendency to reduction in cumulative food intake. For the first time, our results indicate physical exercise can increase PI3k‐p110α protein content in the hypothalamus of obese mice and regulate food intake.
Antiemetic medication efficacy during EPOCH and R-EPOCH treatment

Introduction This study aims to determine the adequacy of current institutional standard practice for CINV prophylaxis for EPOCH and R-EPOCH at The Ohio State University James Cancer Hospital. Methods Single-center, retrospective analysis was performed including all patients receiving EPOCH or R-EPOCH chemotherapy for Non-Hodgkin’s lymphomas from 1/1/2012 to 6/30/2017. The primary endpoint was rate of CINV events, which included usage of more than 50 percent of available doses of breakthrough antiemetics while inpatient, hospitalization due to CINV or related complications, or adjustments made to the CINV prophylactic or breakthrough regimen during current or subsequent cycles. Secondary endpoints included determining prescriber adherence to institutional standard CINV prophylaxis, characterization of adjustments to the antiemetic regimen following the incidence of CINV, and identification of high-risk patients that may benefit from additional CINV prophylaxis. Results Of 111 patients, 54 (48.6%) experienced CINV events with any cycle of EPOCH or R-EPOCH chemotherapy. Of those patients, 17 (31.5%) received institutional standard CINV prophylaxis at baseline, 8 (14.8%) received additional scheduled antiemetics, and 26 (48.1%) were prescribed additional breakthrough antiemetics with their first cycle of EPOCH or R-EPOCH. Younger age, diagnosis of anxiety, and previous susceptibility to nausea were significantly associated with CINV events. Conclusion This study illustrates the inadequacy of current institutional standard for CINV prophylaxis for patients receiving EPOCH and R-EPOCH, highly emetogenic chemotherapy regimens. With nearly half of included patients experiencing CINV events, and most initially receiving more than our standard prophylaxis, changes to our standard antiemetics used with this chemotherapy regimen are needed.
Astrocyte-Selective Volume Increase in Elevated Extracellular Potassium Conditions Is Mediated by the Na+/K+ ATPase and Occurs Independently of Aquaporin 4

Astrocytes and neurons have been shown to swell across a variety of different conditions, including increases in extracellular potassium concentration (^[K+]o). The mechanisms involved in the coupling of K+ influx to water movement into cells leading to cell swelling are not well understood and remain controversial. Here, we set out to determine the effects of ^[K+]o on rapid volume responses of hippocampal CA1 pyramidal neurons and stratum radiatum astrocytes using real-time confocal volume imaging. First, we found that elevating [K+]o within a physiological range (to 6.5 mM and 10.5 mM from a baseline of 2.5 mM), and even up to pathological levels (26 mM), produced dose-dependent increases in astrocyte volume, with absolutely no effect on neuronal volume. In the absence of compensating for addition of KCl by removal of an equal amount of NaCl, neurons actually shrank in ^[K+]o, while astrocytes continued to exhibit rapid volume increases. Astrocyte swelling in ^[K+]o was not dependent on neuronal firing, aquaporin 4, the inwardly rectifying potassium channel Kir 4.1, the sodium bicarbonate cotransporter NBCe1, , or the electroneutral cotransporter, sodium-potassium-chloride cotransporter type 1 (NKCC1), but was significantly attenuated in 1 mM barium chloride (BaCl2) and by the Na+/K+ ATPase inhibitor ouabain. Effects of 1 mM BaCl2 and ouabain applied together were not additive and, together with reports that BaCl2 can inhibit the NKA at high concentrations, suggests a prominent role for the astrocyte NKA in rapid astrocyte volume increases occurring in ^[K+]o. These findings carry important implications for understanding mechanisms of cellular edema, regulation of the brain extracellular space, and brain tissue excitability.