Miracle-dz/UniFAR-FTUs huggingface dataset:
Older Men’s Definitions of Frailty – The Manitoba Follow-up Study

RÉSUMÉ Introduction: Peu de recherches empiriques ont été réalisées sur les définitions non cliniques de la fragilité. Objectifs : 1. Explorer comment les hommes plus âgés définissent la fragilité, et 2. Explorer si ces définitions correspondent aux définitions cliniques de la fragilité qui sont couramment utilisées. Méthodes : Analyses des réponses à des questions ouvertes d’un sondage présenté dans le cadre d’une étude de cohorte prospective réalisée chez des hommes âgés qui avaient travaillé comme aviateurs. Les définitions de la fragilité ont été recueillies et groupées en fonction de thèmes. Résultats : 147 hommes (âge moyen : 93 ans) ont répondu au sondage. Une grande hétérogénéité a été observée dans les définitions de la fragilité recueillies chez ces participants, et aucun des thèmes de la fragilité ne pouvait être qualifié de prédominant. Les incapacités dans les activités de la vie quotidienne étaient le thème le plus fréquemment évoqué. Aucune correspondance ne pouvait être établie entre les définitions de la fragilité énoncées par les hommes âgés et les théories médicales couramment utilisées pour la fragilité. Conclusions : La plupart des hommes âgés pensent que la fragilité est un problème important, bien que leurs définitions de la fragilité diffèrent. La fragilité se manifesterait d’une manière hétérogène et affecterait différemment chaque individu. ABSTRACT Background: There is little empirical research into lay definitions of frailty. Objectives: (1) To explore the definitions of frailty among older men, and (2) to explore if these definitions match commonly used clinical definitions of frailty. Methods: Analysis of open-ended questions to survey data from a prospective cohort study of older airmen. The definitions of frailty were elicited, and grouped according to themes. Results: 147 men responded (mean age: 93). There was considerable heterogeneity in older men’s’ definitions of frailty, and no theme of frailty was predominant. The most common theme was impairment in activities of daily living. Older men’s’ definition of frailty was not consistent with any commonly used medical theory of frailty. Conclusions: Most older men think frailty is important, but their definitions are not consistent. Frailty may be a heterogeneous experience, which different people experience differently.
Oxymatrine suppresses the growth and invasion of MG63 cells by up-regulating PTEN and promoting its nuclear translocation

Studies demonstrated that reduced PTEN levels are associated with poor prognoses of osteosarcoma. The nuclear localization of PTEN is important for its tumor suppressive function. Equally importantly, PTEN is the most significant negative regulator of PI3K/Akt signaling cascade, the constitutively activated pathway in osteosarcoma. In our study MG63 cells and U2OS cells were treated with the indicated concentrations of oxymatrine, in order to find the inhibition of oxymatrine to cells. We found the functions of oxymatrine on proliferation, apoptosis and invasion in cells. Oxymatrine could increase the expression of PTEN and promote its nuclear translocation in MG63 cells. In addition, oxymatrine could induce cell cycle arrest in G1 phase and apoptosis of MG63 cells. The migration and invasion potential of MG63 cells were also markedly inhibited by oxymatrine. Oxymatrine could suppress the growth and invasion of MG63 human osteosarcoma cells by up-regulating PTEN and promoting its nuclear translocation and inhibiting PI3K/Akt signaling pathway.
The Challenges of Analysing Highly Diverse Picobirnavirus Sequence Data

The reliable identification and classification of infectious diseases is critical for understanding their biology and controlling their impact. Recent advances in sequencing technology have allowed insight into the remarkable diversity of the virosphere, of which a large component remains undiscovered. For these emerging or undescribed viruses, the process of classifying unknown sequences is heavily reliant on existing nucleotide sequence information in public databases. However, due to the enormous diversity of viruses, and past focus on the most prevalent and impactful virus types, databases are often incomplete. Picobirnaviridae is a dsRNA virus family with broad host and geographic range, but with relatively little sequence information in public databases. The family contains one genus, Picobirnavirus, which may be associated with gastric illness in humans and animals. Little further information is available due in part to difficulties in identification. Here, we investigate diversity both within the genus Picobirnavirus and among other dsRNA virus types using a combined phylogenetic and functional (protein structure homology-modelling) approach. Our results show that diversity within picobirnavirus exceeds that seen between many other dsRNA genera. Furthermore, we find that commonly used practices employed to classify picobirnavirus, such as analysis of short fragments and trimming of sequences, can influence phylogenetic conclusions. The degree of phylogenetic and functional divergence among picobirnavirus sequences in our study suggests an enormous undiscovered diversity, which contributes to the undescribed “viral dark matter” component of metagenomic studies.
Serious Adverse Events Reported with Dietary Supplement Use in the United States: A 2.5 Year Experience

Abstract Dietary supplement marketers assure the safety of their products by complying with current good manufacturing practices and a host of federal regulations, including those enforced by the Food and Drug Administration (FDA). Post-market surveillance is a key part of identifying safety problems associated with dietary supplement products. FDA requires dietary supplement marketers to provide a domestic address or phone number on product labels for consumers, family members, or health care professionals to report adverse events (AEs) associated with product use and to report all serious adverse events (SAEs) to the agency within 15 business days of receipt. We aimed to evaluate the characteristics of AEs reported with dietary supplement use, including dietary supplement type and Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) that occur with reported SAEs. A total of 41,121 unique adverse event cases reported to two large, U.S.-based dietary supplement marketers in a 2.5-year period (March 1, 2014–August 31, 2016) were assessed for seriousness using established criteria. Each SAE was assigned one or more MedDRA preferred terms and system organ classes (SOC). The types of supplements most responsible for SAEs were assessed. Of the 41,121 AE cases reported, 203 (0.48%) were SAEs. SAEs tended to occur with products marketed for weight loss (69.0%) and glycemic control (19.2%). SAEs occurred most commonly in the cardiovascular, gastrointestinal, and nervous system disorder SOCs. The percentage of SAEs reported to dietary supplement marketers is low, predominantly among consumers of two types of supplements. Further study is needed among a larger cohort of supplement users to determine causal associations between types of supplement products and serious adverse events.
EMF exposure variation among MRI sequences from pediatric examination protocols

The magnetic resonance imaging (MRI) exposure environment is unique due to the mixture and intensity of magnetic fields involved. Current safety regulations are based on well‐known acute effects of heating and neuroexcitation while the scientific grounds for possible long‐term effects from MRI exposure are lacking. Epidemiological research requires careful exposure characterization, and as a first step toward improved exposure assessment we set out to characterize the MRI‐patient exposure environment. Seven MRI sequences were run on a 3‐Tesla scanner while the radiofrequency and gradient magnetic fields were measured inside the scanner bore. The sequences were compared in terms of 14 different exposure parameters. To study within–sequence variability, we varied sequence settings such as flip angle and slice thickness one at a time, to determine if they had any impact on exposure endpoints. There were significant differences between two or more sequences for all fourteen exposure parameters. Within–sequence differences were up to 60% of the corresponding between‐sequence differences, and a 5–8 fold exposure increase was caused by variations in flip angle, slice spacing, and field of view. MRI exposure is therefore not only sequence‐specific but also patient‐ and examination occurrence‐specific, a complexity that requires careful consideration for an MRI exposure assessment in epidemiological studies to be meaningful. Bioelectromagnetics. 40:3–15, 2019. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.
Improving transparency and scientific rigor in academic publishing

Progress in basic and clinical research is slowed when researchers fail to provide a complete and accurate report of how a study was designed, executed, and the results analyzed. Publishing rigorous scientific research involves a full description of the methods, materials, procedures, and outcomes. Investigators may fail to provide a complete description of how their study was designed and executed because they may not know how to accurately report the information or the mechanisms are not in place to facilitate transparent reporting. Here, we provide an overview of how authors can write manuscripts in a transparent and thorough manner. We introduce a set of reporting criteria that can be used for publishing, including recommendations on reporting the experimental design and statistical approaches. We also discuss how to accurately visualize the results and provide recommendations for peer reviewers to enhance rigor and transparency. Incorporating transparency practices into research manuscripts will significantly improve the reproducibility of the results by independent laboratories.
Diverse effects of natural antioxidants on cyclosporin cytotoxicity in rat renal tubular cells.

BACKGROUND As is well known, the use of the immunosuppressive drug cyclosporin A (CsA) is partially restricted by its nephrotoxic effects, which include early changes in haemodynamics followed by irreversible injuries to the renal tubules. Although the mechanisms responsible for these side effects are poorly understood, an involvement of reactive oxygen species (ROS) has been suggested. In this study, we selected three natural antioxidants, resveratrol, hydroxytyrosol and vitamin E, on the basis of their scavenging capabilities, and tested their protective effects against CsA toxicity. METHODS Immortalized rat tubular cells (RPTc) were used as the model system. Cell viability was checked with trypan blue assay, and free radical formation was measured using the fluorescent probe 2,7-dichlorofluorescein (DCF). We evaluated several oxidative stress parameters, including phospholipid peroxidation products, glutathione levels and oxygenase expression. RESULTS Incubation of RPTc with 25 muM CsA induced a significant decrease in cell viability paralleled by intracellular ROS formation and alterations in lipid peroxidation. There was also an imbalance of glutathione redox state as well as upregulation of heme oxygenase-1 (HO-1). The three antioxidants, at micromolar concentration, quantitatively prevented the ROS-activated DCF fluorescent signal and membrane lipid peroxidation. Both hydroxytyrosol and resveratrol strengthened the CsA induction of HO-1 expression. Moreover, vitamin E and resveratrol counteracted CsA-induced changes in the glutathione redox state via different mechanisms, whereas hydroxytyrosol was completely ineffective. Similarly, CsA-dependent nephrotoxicity was prevented by vitamin E, while resveratrol only exerted partial protection, and hydroxytyrosol showed no protective effects. CONCLUSION Our results indicate that the diverse cytoprotective effects of the antioxidants tested in these studies were not directly related to their scavenging capabilities. These findings confirm a key role for glutathione in protecting cells from CsA-induced adverse effects and do not support a direct link between CsA-mediated ROS generation and adverse renal effects.
Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014‐2018)

Background Three flaviviruses (equine pegivirus [EPgV]; Theiler's disease–associated virus [TDAV]; non‐primate hepacivirus [NPHV]) and equine parvovirus (EqPV‐H) are present in equine blood products; the TDAV, NPHV, and EqPV‐H have been suggested as potential causes of serum hepatitis. Objective To determine the prevalence of these viruses in horses with equine serum hepatitis. Animals Eighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals. Methods In the prospective case study, liver, serum, or both samples were tested for EPgV, TDAV, NPHV, and EqPV‐H by PCR. Results Both liver tissue and serum were tested for 6 cases, serum only for 8 cases, and liver only for 4 cases. Twelve horses received tetanus antitoxin (TAT) 4‐12.7 weeks (median = 8 weeks), 3 horses received commercial equine plasma 6‐8.6 weeks, and 3 horses received allogenic stem cells 6.4‐7.6 weeks before the onset of hepatic failure. All samples were TDAV negative. Two of 14 serum samples were NPHV‐positive. Six of 14 serum samples were EPgV‐positive. All liver samples were NPHV‐negative and EPgV‐negative. EqPV‐H was detected in the serum (N = 8), liver (N = 4), or both samples (N = 6) of all 18 cases. The TAT of the same lot number was available for virologic testing in 10 of 12 TAT‐associated cases, and all 10 samples were EqPV‐H positive. Conclusions and Clinical Importance We demonstrated EqPV‐H in 18 consecutive cases of serum hepatitis. EPgV, TDAV, and NPHV were not consistently present. This information should encourage blood product manufacturers to test for EqPV‐H and eliminate EqPV‐H–infected horses from their donor herds.
Laparoscopy for blunt abdominal trauma: a challenging endeavor

Background and Aims: Laparoscopy in blunt abdominal trauma is challenging because of multiple associated injuries, higher trauma score values and higher morbidity and mortality, as compared with patients with penetrating abdominal trauma. The aim of this study was to investigate the role of laparoscopy in the management of blunt abdominal trauma patients and to highlight related challenges. Material and Methods: Over a 4-year period, patients managed laparoscopically for blunt abdominal trauma were retrospectively analyzed. Perioperative details, indications for laparoscopy and conversion, complications, and length of hospital stay were discussed. Results: A total of 35 stable patients underwent laparoscopy. The mean Injury Severity Score was 12 (4–38). Therapeutic laparoscopy was performed in 15 (56%) and diagnostic in 12 (44%) patients. Eight (23%) patients were converted to therapeutic laparotomy. Intraoperative bleeding, complex injuries, visualization problem, and equipment failure necessitated conversion. Three (30%) patients with negative computed tomography scan had therapeutic laparoscopy for mesenteric injuries. There were no missed injuries. The mean length of hospital stay was 11 days in both groups. Conclusion: Laparoscopy for stable patients is feasible and safe. Multiple injuries make laparoscopy more difficult, and advanced laparoscopic skills are required. The conversion rate is high; however, the non-therapeutic laparotomies were completely eliminated in this study.
Two-stage versus single-stage procedure for the management of cholecystocholedocholithiasis in elderly patients: a retrospectively cohort study.

BACKGROUND there is an increasing incidence rate of cholecysto-choledocholithiasis associated with the increasing proportion of senile individuals. METHODS a total of 100 elderly patients (over 80 years of age) suffering both from cholelithiasis and choledocholithiasis were retrospectively studied from January 2010 to December 2016. Patients were scheduled for either a single-stage or two-stage procedure. The LCBDE group (n = 54) included cases that underwent a single stage procedure of laparoscopic exploration of the common bile duct combined with cholecystectomy. The ERCP/EST group (n = 46) included cases that underwent a two stage procedure of preoperative endoscopic retrograde cholangiopancreaticography with endoscopic sphincterotomy followed by cholecystectomy. Comorbidity conditions, presenting symptoms, bile duct clearance, length of hospital stay and the frequency of procedural, postoperative and long-term complications were recorded. RESULTS the LCBDE group had a higher stones clearance rate than the ERCP/EST group (100.0% vs 89.1%, p < 0.05). Postoperative complications and hospitalization length were comparable in the two groups (p > 0.05). There were more procedural complications in the ERCP/EST group than in the LCBDE group (10.8% vs 0%, p < 0.05). Furthermore, a patient in the ERCP/EST group died due to duodenal perforation. More patients in the ERCP/EST group experienced long-term complications than those in the LCBDE group (23.9% vs 3.7%, p < 0.05) during a mean follow-up period of 28.4 months. CONCLUSIONS the single-stage procedure is a safe and effective technique for elderly patients with cholecysto-choledocholithiasis. LCBDE provides a good stone clearance rate with few long term complications.
Elevated truncated oxidized phospholipids as a factor exacerbating ALI in the aging lungs

As mechanisms controlling redox homeostasis become impaired with aging, exaggerated oxidant stress may cause disproportional oxidation of cell membranes and circulating phospholipids (PLs), leading to the formation of truncated oxidized PL products (Tr‐OxPLs), which exhibit deleterious effects. This study investigated the role of elevated Tr‐OxPLs as a factor exacerbating inflammation and lung barrier dysfunction in an animal model of aging. Mass spectrometry analysis of Tr‐OxPL species in young (2–4 mo) and aging (18–24 mo) mice revealed elevated basal levels of several products [1‐palmitoyl‐2‐(5‐oxovaleroyl)‐sn‐glycero‐phosphocholine (POVPC), 1‐palmitoyl‐2‐glutaroyl‐sn‐glycero‐phosphocholine, lysophosphocholine, 1‐palmitoyl‐2‐(9‐oxo‐nonanoyl)‐sn‐glycero‐3‐phosphocholine, 1‐palmitoyl‐2‐azelaoyl‐sn‐glycero‐3‐phosphocholine, O‐1‐O‐palmitoyl‐2‐O‐(5,8‐dioxo‐8‐hydroxy‐6‐octenoyl)‐l‐glycero‐3‐phosphocholine, and others] in the aged lungs. An intratracheal (i.t.) injection of bacterial LPS caused increased generation of Tr‐OxPLs in the lungs but not in the liver, with higher levels detected in the aged group. In addition, OxPLs clearance from the lung tissue after LPS challenge was delayed in the aged group. The impact of Tr‐OxPLs on endothelial cell (EC) barrier compromise under inflammatory conditions was further evaluated in the 2‐hit cell culture model of acute lung injury (ALI). EC barrier dysfunction caused by cell treatment with a cytokine mixture (CM) was augmented by cotreatment with low‐dose Tr‐OxPLs, which did not significantly affect endothelial function when added alone. Deleterious effects of Tr‐OxPLs on inflamed ECs stimulated with CM were associated with further weakening of cell junctions and more robust EC hyperpermeability. Aged mice injected intratracheally with TNF‐α exhibited a more pronounced elevation of cell counts and protein content in bronchoalveolar lavage (BAL) samples. Interestingly, intravenous administration of low POVPC doses—which did not affect BAL parameters alone in young mice exposed to i.t. TNF‐α challenge—augmented lung injury to the levels observed in aged mice stimulated with TNF‐α alone. Inhibition of Tr‐OxPL generation by ectopic expression of PL‐specific platelet‐activating factor acetylhydrolase 2 (PAFAH2) markedly reduced EC dysfunction induced by CM, whereas PAFAH2 pharmacologic inhibition augmented deleterious effects of cytokines on EC barrier function. Moreover, exacerbating effects of PAFAH2 inhibition on TNF‐α–induced lung injury were observed in vivo. These results demonstrate an age‐dependent increase in Tr‐OxPL production under basal conditions and augmented Tr‐OxPL generation upon inflammatory stimulation, suggesting a major role for elevated Tr‐OxPLs in more severe ALI and delayed resolution in aging lungs. —Ke, Y. , Karki, P., Kim, J., Son, S. , Berdyshev, E. , Bochkov, V. N. , Birukova, A. A. , Birukov, K. G. Elevated truncated oxidized phospholipids as a factor exacerbating ALI in the aging lungs. FASEB J. 33, 3887–3900 (2019). www.fasebj. org
Trekking exercise promotes cardiovascular health and fitness benefits in older obese women

Trekking includes downhill walking and enhances lower limb strength. Muscle fitness is a predictor of mortality and is associated with cardiovascular risk factors in adults. The purpose of this study was to investigate the effects of trekking on cardiovascular health and fitness in older obese women. The participants were randomly assigned to an exercise group (EG, n= 32) and a control group (CG, n= 48). The EG participated in the trekking program for 12 weeks, 3 times per week, and 90 min per session, at a moderate intensity. Cardiovascular health (BMI, percentage of body fat, blood pressure, glucose, triglycerides, and total cholesterol) and fitness (muscle strength, muscle endurance, balance, and flexibility) were measured before and after the 12-week program. A twoway repeated ANOVA was used to compare and analyze the group differences. Body weight, systolic blood pressure, and muscle strength were significantly different between the groups. These results indicate that trekking played a significant role in the reduction of weight and systolic blood pressure in obese women. The results of this study can be utilized to reduce cardiovascular risk factors associated with aging.
CORRELATED MORPHOMETRIC AND BIOCHEMICAL STUDIES ON THE LIVER CELL

The changes occurring in rat hepatocytes during a 5 day period of treatment with phenobarbital were determined by morphometric and biochemical methods, particular attention being paid to the endoplasmic reticulum. The hepatocytic cytoplasm played an overwhelming part in the liver hypertrophy, while the hepatocytic nuclei contributed to only a moderate extent. The endoplasmic reticulum accounted for more than half of the increase in cytoplasmic volume. The increase in the volume and number of hepatocytic nuclei in the course of phenobarbital treatment was associated with changes in the ploidy pattern. Until the 2nd day of treatment both the rough-surfaced endoplasmic reticulum (RER) and the smooth-surfaced endoplasmic reticulum (SER) participated in the increase in volume and surface of the whole endoplasmic reticulum (ER). Subsequently, the values for RER fell again to control levels, whereas those for SER continued to increase, with the result that by the 5th day of treatment the SER constituted the dominant cytoplasmic element. The specific volume of mitochondria and microbodies (peroxisomes) remained constant throughout the duration of the experiment, while that of the dense bodies increased. The specific number of mitochondria and microbodies displayed a significant increase, associated with a decrease in their mean volume. The phenobarbital-induced increase in the phospholipid and cytochrome P-450 content of the microsomes, as well as in the activities of microsomal reduced nicotinamide-adenine dinucleotide phosphate-cytochrome c reductase and N-demethylase, was correlated with the morphometric data on the endoplasmic reticulum.