Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of blood pressure on 3-month functional outcome in the subacute stage of ischemic stroke

ABSTRACT Objective: We aimed to study various measures of blood pressure (BP) in the subacute phase of ischemic stroke to determine whether any of them predicted clinical outcome. Methods: In this retrospective observational study, a consecutive series of patients hospitalized for ischemic stroke within 48 hours of onset were enrolled. The subacute stage of stroke was defined as the time period from 72 hours of symptom onset to discharge or transfer. During this period, mean, maximum, maximum − minimum, SD, and coefficient of variation of systolic BP (SBP) and diastolic BP (DBP) were determined. A baseline severity-adjusted analysis was performed using each patient’s 3-month modified Rankin Scale score as the primary outcome. Results: Among a total of 2,271 patients, the median number of BP measurements was 34 per person and the median interval from onset to discharge was 8.7 days. Measures of variability of BP were associated with poor outcome. One SD increase of maximum − minimum (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12–1.42), SD (OR, 1.20; 95% CI, 1.07–1.34), or coefficient of variation (OR, 1.21; 95% CI, 1.09–1.35) for SBP, but not mean level of SBP (OR, 0.92; 95% CI, 0.79–1.07), was independently associated with poor outcome. Results were similar for DBP. Conclusion: This study shows that variability of BP, but not average BP in the subacute stage of ischemic stroke, is associated with functional outcome at 3 months after stroke onset.
Sulforaphane accelerates acetaldehyde metabolism by inducing aldehyde dehydrogenases: relevance to ethanol intolerance.

AIMS Many East Asians are highly intolerant to even modest alcohol consumption. These individuals accumulate acetaldehyde, the primary metabolite of ethanol, because of a genetic polymorphism of aldehyde dehydrogenase (ALDH) that metabolizes acetaldehyde to nontoxic acetate. The aim of these studies is to upregulate ALDH by dietary means, thereby reducing acetaldehyde toxicity. METHODS Sulforaphane [SF, 1-isothiocyano-4-(methylsulfinyl)butane] derived from its glucosinolate precursor contained in cruciferous vegetables and related inducers of the Keap1/Nrf2/ARE pathway were assessed for their potencies to induce ALDH in murine hepatoma Hepa1c1c7 cells. Inducer potencies for ALDH were compared with those for NQO1, a prototypical cytoprotective enzyme present downstream of the Keap1/Nrf2/ARE pathway. SF (5 or 20 µmol/day) was fed to CD-1 mice for 7 days prior to a single administration of ethanol, and then ALDH induction in organs and pharmacokinetics of acetaldehyde was examined. RESULTS In addition to SF, other electrophiles, including many Michael reaction acceptors, induce ALDH. Potencies of these agents as inducers parallel their activities in inducing NQO1, and are also dependent on Nrf2. In mice, in vivo, feeding of SF induced tissue ALDH and dramatically increased (doubled) the rate of elimination of acetaldehyde arising from the administration of ethanol. CONCLUSION SF and other edible phytochemicals may ameliorate the alcohol intolerance of individuals who are polymorphic with respect to ALDH.
Positron Emission Tomography Correlates of Visually-Scored Electroencephalographic Waveforms During Non-Rapid Eye Movement Sleep

Visually-scored, non-Rapid Eye Movement (REM) sleep electroencephalographic (EEG) waveform activity for each 30-s sleep scored epoch—including the number of sleep spindles, the number of K-complexes, and the percentage of delta waves occupying the epoch—was correlated with H215O positron emission tomography. Sleep spindle correlations included positive correlations in the thalamus and right hippocampus. K-complex correlations included positive correlations in the frontomedian prefrontal cortex and cerebellum. Delta wave correlations included negative correlations in the thalamus, frontomedian prefrontal cortex, dorsal pons, and primary visual cortex. Each pattern of correlations may suggest a functional significance for these waveforms that relates to a waking outcome.
The use of plasma HIV RNA as a study endpoint in efficacy trials of antiretroviral drugs.

OBJECTIVES To evaluate the utility of HIV RNA as an endpoint in antiretroviral efficacy studies. DESIGN Data collected from antiretroviral efficacy trials were analyzed to explore relationships between clinical progression and the magnitude, nadir and duration of HIV RNA reductions. The proportion of patients suppressing HIV RNA below assay quantification, time to maximal virologic response, and loss of virologic response in relation to pretreatment characteristics were also analyzed. METHODS Analyses were conducted using data from individual antiretoviral efficacy trials or groups of trials that studied similar types of drug regimens and used similar HIV RNA assays. Treatment regimens were pooled for most analyses. Clinical progression was defined as the occurrence of an AIDS-defining event (essentially Centers of Disease Control criteria) or death. RESULTS Treatment-induced reductions in HIV RNA approximating total assay variability of about 0.5 log10 copies/ml were associated with decreases in the risk of clinical progression. Larger and more sustained reductions in HIV RNA were directly associated with lower risks for disease progression. Lower initial HIV RNA reductions were associated with more durable HIV RNA suppression. CONCLUSIONS For antiretoviral efficacy studies, plasma HIV RNA is a suitable study endpoint that is likely to predict a decreased risk for AIDS progression and death. Because greater and more sustained reductions in HIV RNA appear to confer greater reductions in clinical risk, maintaining maximal suppression of plasma HIV RNA, particularly below the limits of assay quantification, appears to be a rigorous benchmark for assessing the efficacy of antiretroviral regimens.
Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life.

OBJECTIVE This study was designed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults. METHOD A double-blind, parallel group design was used to compare 210 outpatients, 60 years of age and older, who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18. The patients were randomly assigned to 12 weeks of treatment with either sertraline (50-150 mg/day) or nortriptyline (25-100 mg/day). RESULTS The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate, whereas sertraline was associated with a nonsignificant decrease. Efficacy of both drugs was similar for both treatments at all time points, with 71.6% (N=53 of 74) of the sertraline-treated patients and 61.4% (N=43 of 70) of the nortriptyline-treated patients achieving responder status by week 12. Time to response was also similar, with more than 75% of the improvement in scores on the Hamilton depression scale having occurred by week 6. Secondary efficacy measures (posttreatment measures of cognitive function, memory, and quality of life) revealed a significant advantage for sertraline treatment. CONCLUSIONS Primary efficacy measures showed sertraline and nortriptyline to be similarly effective. With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group. The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment.
Relation of nutrition, body composition and physical activity to skeletal development: a cross-sectional study in preadolescent females.

OBJECTIVE To examine the relation of anthropometric and growth parameters (weight, stature, body composition, age, and skeletal age), nutritional factors, and physical activity to the total body and radius bone mineral density and content and radiogrammetry parameters of the second metacarpal. STUDY DESIGN The study was a cross-sectional evaluation of 456 healthy, Caucasian girls, ages 8 to 13 years. Multiple regression models were created based on Cp statistics to determine the association between bone parameters and various independent variables. RESULTS Mean calcium intake was 956+/-381 mg/day, about 20% below the RDA of 1200 mg/day and about 36% below the threshold intake of approximately 1500 mg/day. The most significant predictors for total body and radius bone mineral density were corresponding bone areas, lean body mass, body fat, skeletal age, dietary calcium, and stature (only for total body) with corresponding R2(adjusted) of 48% and 36%. The total body and radius bone mineral content was positively associated with corresponding bone areas, lean body mass, body fat, calcium intake, and skeletal age with corresponding R2(adjusted) of 86% and 72%. Energy expenditure (corrected for BMI) was stratified into quartiles and bone mass parameters were distributed accordingly. A statistically significant difference in total body and radius bone mineral density and content was noted between the fourth and lower quartiles (ANOVA, p<0.05 to p<0.0001). CONCLUSION The most significant predictors of bone mass in preadolescent females evaluated in this study are bone area, lean body mass, body fat, skeletal age and dietary calcium.
Percutaneous coronary intervention versus bypass grafting in left main coronary artery disease.

Without revascularization, patients with left main coronary artery disease (LMCAD) have a poor prognosis (1). There is a clear survival benefit from revascularization over medical management (1). Percutaneous coronary intervention (PCI) has been traditionally deferred in preference for coronary artery bypass grafting (CABG), due to the anatomic complexity (2). However, with the evolution of drug-eluting stents (DES), there has been a reduction in restenosis rates and mortality, repeat revascularization and major adverse cardiac and cerebrovascular events (MACCE) compared with bare metal stents (3). There has been a renewed interest in expanding the indication for PCI in patients with LMCAD (3). Despite this heightened interest in the comparative outcomes of DES versus CABG for patients with LMCAD, the choice for the optimal revascularization technique remains controversial.
Modulation of humoral immune responses and inhibition of proinflammatory cytokines and nitric oxide production by 10-methoxycanthin-6-one

Plant-derived natural products such as alkaloids, flavonoids, terpenoids, and polysaccharides have received considerable attention in recent years due to their diverse pharmacological properties such as immunomodulatory, anti-inflammatory, cytotoxic, cancer chemopreventive effects, and so on. 10-Methoxycanthin-6-one, a β-carboline alkaloid from the medicinal plant Aerva lanata, was assessed for immunomodulatory activity in Balb/c mice. Intraperitoneal administration of five doses of the compound at 0.5 mg/kg body weight was found to enhance the total WBC count (13,975.50 ± 324.27 cells/mm3 on the 12th day), bone marrow cellularity (23.08 ± 0.86 × 106 cells/femur), and number of α-esterase-positive cells (1283.16 ± 21.10 cells/4000 cells). Treatment with the compound along with the antigen, sheep red blood cells, produced an enhancement in the circulating antibody titer (1024 on Days 12 and 15) and the number of plaque-forming cells (PFC) in the spleen. In treated group, maximum number of PFC (264.83 PFC/106 spleen cells) was observed on the sixth day after antigen administration. At the same time, administration of 10-methoxycanthin-6-one could significantly reduce the elevated levels of proinflammatory cytokines and nitric oxide production by lipopolysaccharide (LPS)-stimulated macrophages. There was also a significant reduction in the mRNA levels of inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor alpha (TNF)-α, and interleukin (IL)-1β and IL-6 in LPS-stimulated macrophages after treatment with 10-methoxycanthin-6-one.
Development and Validation of the Keele Musculoskeletal Patient Reported Outcome Measure (MSK-PROM)

Objective To develop and validate a patient report outcome measure (PROM) for clinical practice that can monitor health status of patients with a range of musculoskeletal (MSK) disorders. Methods Constructs for inclusion in the MSK-PROM were identified from a consensus process involving patients with musculoskeletal conditions, clinicians, purchasers of healthcare services, and primary care researchers. Psychometric properties of the brief tool, including face and construct validity, repeatability and responsiveness were assessed in a sample of patients with musculoskeletal pain consulting physiotherapy services in the United Kingdom (n=425). Results The consensus process identified 10 prioritised domains for monitoring musculoskeletal health status: pain intensity, quality of life, physical capacity, interference with social/leisure activities, emotional well-being, severity of most difficult thing, activities and roles, understanding independence, and overall impact. As the EuroQol (EQ-5D-5L) is a widely adopted PROMs tool and covers the first four domains listed, to reduce patient burden to a minimum the MSK-PROM was designed to capture the remaining six prioritised domains which are not measured by the EQ-5D-5L. The tool demonstrated excellent reliability, construct validity, responsiveness and acceptability to patients and clinicians for use in clinical practice. Conclusion We have validated a brief patient reported outcome measure (MSK-PROM) for use in clinical practice to measure musculoskeletal health status and monitor outcomes over time using domains that are meaningful to patients and sensitive to change. Further work will establish whether the MSK-PROM is useful in other musculoskeletal healthcare settings.
Estrogens enhance myoblast differentiation in facioscapulohumeral muscular dystrophy by antagonizing DUX4 activity

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that is characterized by extreme variability in symptoms, with females being less severely affected than males and presenting a higher proportion of asymptomatic carriers. The sex-related factors involved in the disease are not known. Here, we have utilized myoblasts isolated from FSHD patients (FSHD myoblasts) to investigate the effect of estrogens on muscle properties. Our results demonstrated that estrogens counteract the differentiation impairment of FSHD myoblasts without affecting cell proliferation or survival. Estrogen effects are mediated by estrogen receptor &bgr; (ER&bgr;), which reduces chromatin occupancy and transcriptional activity of double homeobox 4 (DUX4), a protein whose aberrant expression has been implicated in FSHD pathogenesis. During myoblast differentiation, we observed that the levels and activity of DUX4 increased progressively and were associated with its enhanced recruitment in the nucleus. ER&bgr; interfered with this recruitment by relocalizing DUX4 in the cytoplasm. This work identifies estrogens as a potential disease modifier that underlie sex-related differences in FSHD by protecting against myoblast differentiation impairments in this disease.
Tissue-Specific Regulation of Gibberellin Biosynthesis in Developing Pea Seeds1[W][OA]

Previous work suggests that gibberellins (GAs) play an important role in early seed development. To more fully understand the roles of GAs throughout seed development, tissue-specific transcription profiles of GA metabolism genes and quantitative profiles of key GAs were determined in pea (Pisum sativum) seeds during the seed-filling development period (8–20 d after anthesis [DAA]). These profiles were correlated with seed photoassimilate acquisition and storage as well as morphological development. Seed coat growth (8–12 DAA) and the subsequent dramatic expansion of branched parenchyma cells were correlated with both transcript abundance of GA biosynthesis genes and the concentration of the growth effector GA, GA1. These results suggest GA1 involvement in determining the rate of seed coat growth and sink strength. The endosperm’s PsGA20ox transcript abundance and the concentration of GA20 increased markedly as the endosperm reached its maximum volume (12 DAA), thus providing ample GA20 substrate for the GA 3-oxidases present in both the embryo and seed coat. Furthermore, PsGA3ox transcript profiles and trends in GA1 levels in embryos at 10 to 16 DAA and also in embryo axes at 18 DAA suggest localized GA1-induced growth in these tissues. A shift from synthesis of GA1 to that of GA8 occurred after 18 DAA in the embryo axis, suggesting that deactivation of GA1 to GA8 is a likely mechanism to limit embryo axis growth and allow embryo maturation to proceed. We hypothesize that GA biosynthesis and catabolism are tightly regulated to bring about the unique developmental events that occur during seed growth, development, and maturation.
Expression of a Modified Form of CD4 Results in the Release of an Anti-HIV Factor Derived from the Env Sequence1

We have studied the inhibitory effect of a CD4 chimera (CD4ε15) on HIV replication. This chimera is retained in the endoplasmic reticulum and traps the HIV envelope precursor gp160, preventing its maturation. Retroviral expression of the chimera strongly inhibited HIV replication even when it is expressed by only a minority of the T cell population. This protective effect on bystander nontransduced cells is mediated by a soluble factor that we identified as a fragment of HIV gp120 envelope protein and accordingly, we named this factor Env-derived antiviral factor (EDAF). Biochemical and immunoreactivity data show that EDAF is comprised of the gp120 C3-C5 regions and indeed, a recombinant protein bearing this sequence reproduces the anti-HIV properties of EDAF. Surprisingly, three tryptic peptides derived from EDAF are homologous but not identical with the corresponding sequences of the HIV isolate used to generate EDAF. We propose that EDAF results from an alternative intracellular processing of the Env protein provoked by its association to CD4ε15 and the selection of the best fitted Env protein sequences contained within the HIV isolate. The presence of EDAF improves the therapeutic potential of the CD4ε15 gene and it opens new possibilities for antiviral treatment and vaccine development.
Activation of the Phagocyte NADPH Oxidase Protein p47 phox

Activation of phagocyte NADPH oxidase requires interaction between p47 phox and p22 phox . p47 phox in resting phagocytes does not bind p22 phox . Phosphorylation of serines in the p47 phox C terminus enables binding to the p22 phox C terminus by inducing a conformational change in p47 phox that unmasks the SH3Adomain. We report that an arginine/lysine-rich region in the p47 phox C terminus binds the p47 phox SH3 domains expressed in tandem (SH3AB) but does not bind the individual N-terminal SH3A and C-terminal SH3Bdomains. Peptides matching amino acids 301–320 and 314–335 of the p47 phox arginine/lysine-rich region block the p47 phox SH3AB/p22 phox C-terminal and p47 phox SH3AB/p47 phox C-terminal binding and inhibit NADPH oxidase activity in vitro. Peptides with phosphoserines substituted for serines 310 and 328 do not block binding and are poor inhibitors of oxidase activity. Mutated full-length p47 phox with aspartic acid substitutions to mimic the effects of phosphorylations at serines 310 and 328 bind the p22 phox proline-rich region in contrast to wild-type p47 phox . We conclude that the p47 phox SH3A domain-binding site is blocked by an interaction between the p47 phox SH3AB domains and the C-terminal arginine/lysine-rich region. Phosphorylation of serines in the p47 phox C terminus disrupts this interaction leading to exposure of the SH3Adomain, binding to p22 phox , and activation of the NADPH oxidase.
Readmission for Infective Endocarditis After Ischemic Stroke or Transient Ischemic Attack

Background and Purpose: Providers vary in their thresholds for obtaining blood cultures in patients with ischemic stroke or transient ischemic attack (TIA). We assessed the rate of missed diagnoses of infective endocarditis (IE) in patients discharged with stroke or TIA before blood culture results could have been available. Methods: Using administrative claims data, we performed a retrospective cohort study of all patients discharged from nonfederal California emergency departments or acute care hospitals from 2005 through 2011 with stroke (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 433.x1, 434.x1, or 436 in any position) or TIA (ICD-9-CM code 435 in the primary diagnosis position). We excluded patients with a length of stay >2 days to focus on those discharged before conclusive blood culture results could have been available. Our outcome was hospitalization within 14 days with a new diagnosis of IE (ICD-9-CM codes 391.1 or 421.x in any position). Results: Among 173 966 eligible patients, 24 were subsequently hospitalized for IE—a readmission rate of 1.4 per 10 000 (95% confidence interval [CI], 0.8-1.9 per 10 000). Multiple logistic regression identified the following potential associations with readmission: prosthetic valve: odds ratio (OR), 15.8 (95% CI, 1.9-129.0); other valvular disease: OR, 1.5 (95% CI, 0.2-10.8); urinary tract infection: OR, 3.5 (95% CI, 1.0-12.3; P = .05). Conclusions: In patients with acute cerebral ischemia discharged before blood culture results could have been available, the rate of subsequent IE was negligible. These findings argue against the liberal use of blood cultures for the routine evaluation of stroke or TIA.
Ergogenic Aids: A Review of Basic Science, Performance, Side Effects, and Status in Sports

The use of drugs and supplements to enhance performance has become a part of mainstream athletics. Many team physicians and sports medicine practitioners are unfamiliar with the benefits and risks of these products and thus are unable to educate young athletes on this topic. In spite of numerous reports on the health risks of anabolic steroid use, 1 to 3 million Americans have used them. Human growth hormone has been tried by up to 5% of 10th graders, although no scientific study has shown that it is an effective performance-enhancing drug. Amphetamines and similar compounds may be the most widely abused drug in baseball; recently, they have come under increased scrutiny in sport. Erythropoietin is a highly effective aerobic enhancer that has been linked to multiple deaths in cyclists and other endurance athletes. The neutraceutical industry, led by supplements such as creatine, ephedra, and androstenedione, remains unregulated by the Food and Drug Administration and has serious issues with quality and side effects. An understanding of these products is essential for the sports medicine practitioner to provide sound, safe advice to the athlete.
Forecasting PM10 in the Bay of Algeciras Based on Regression Models

Different forecasting methodologies, classified into parametric and nonparametric, were studied in order to predict the average concentration of P M 10 over the course of 24 h. The comparison of the forecasting models was based on four quality indexes (Pearson’s correlation coefficient, the index of agreement, the mean absolute error, and the root mean squared error). The proposed experimental procedure was put into practice in three urban centers belonging to the Bay of Algeciras (Andalusia, Spain). The prediction results obtained with the proposed models exceed those obtained with the reference models through the introduction of low-quality measurements as exogenous information. This proves that it is possible to improve performance by using additional information from the existing nonlinear relationships between the concentration of the pollutants and the meteorological variables.