Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal myocardial shortening in aortic stenosis: ready for prime time after 30 years of research?

Aortic valve replacement (AVR) is recommended for patients having severe aortic stenosis (AS) associated with symptoms and/or left ventricular systolic dysfunction defined as left ventricular ejection fraction (LVEF) of less than 50%. Left ventricular dysfunction may, however, develop insidiously in the asymptomatic patient with severe AS and may eventually become irreversible. Accordingly, some recent studies support the realisation of elective surgery in asymptomatic patients with severe AS to improve their long-term survival.1 On the other hand, the risk of operative death associated with elective AVR may outweigh the low risk of sudden death that has been reported in asymptomatic patients. The challenge for the clinician is thus to detect left ventricular contractile dysfunction at an early or subclinical stage so that closer follow-up can be instituted or surgical correction performed to prevent the development of irreversible left ventricular dysfunction and adverse outcomes. In this issue of Heart , Cramariuc et al 2 report the results of an elegant study in which they examined the relationship between myocardial deformation assessed by speckle tracking imaging and left ventricular geometry in patients with AS ( see page 106 ). The main findings of the study are: (1) left ventricular longitudinal myocardial strain is reduced in patients with left ventricular concentric hypertrophy; (2) the extent of longitudinal strain impairment is related to larger left ventricular mass index, higher relative wall thickness ratio (ie, higher degree of concentric remodelling) and more severe stenosis severity. Thirty years ago in 1979, Dumesnil and colleagues3 were the first to report that patients with AS often have selective decreases in left ventricular …
The Factor V Leiden Mutation Is Not a Common Cause of Pregnancy-Induced Hypertension in Japan

Recent studies in Caucasian populations have shown an association of the Leiden mutation in factor V with preeclampsia (PE). It consists of a substitution of a G (G1691) with an A (A1691) at nucleotide position 1691 in exon 10, resulting in arginine instead of glutamine at residue 506 at the factor V cleavage site for activated protein C (APC); it contributes to the resistance to APC. The purpose of this study was to determine whether the Leiden mutation is associated with pregnancy-induced hypertension (PIH), including PE, in Japanese women. We examined the genotypes of factor V of 71 Japanese patients with PIH and 109 controls. None of the 180 Japanese women carried the factor V Leiden mutation. To date, the factor V Leiden mutation is rare and not a common cause of PIH in Japan. The results may suggest that there is a significant ethnic difference in the role of the Leiden mutation in compounding the risk factors in the pathogenesis of PIH between Japanese and Caucasian populations.
Modeling classic female Rett Syndrome in male mice

Classic Rett Syndrome (RTT) is a crippling neurodevelopmental disorder and with an incidence of 1 in 15 000 in females, it is one of the most common causes of childhood mental retardation. After an initial period (6–18 months) of normal childhood development, RTT females experience a devastating and often abrupt developmental regression marked by the loss of speech and purposeful hand movements. Although there is a great deal of variability in the disease phenotype, classic RTT features profound mental handicap accompanied with ataxia, growth retardation, kyphosis, seizures, breathing abnormalities and characteristic hand-wringing movements. In a recent report, Shahbazian et al. have achieved a milestone in our understanding of the X-linked disorder with the refinement and characterization of a gene-targeted mouse that genetically and phenotypically models RTT. The gene responsible for RTT, MECP2, coding for methyl CpG-binding protein 2, was discovered on Xq28 in 1999 after a laborious search of the X-chromosome using exclusion mapping. A variety of mutation types throughout the coding region of MECP2 have been observed in RTT patients who usually carry the mutation spontaneously or in rare cases inherit the mutation in a dominant fashion. RTT is clearly a neurologic disorder and the causative connection with mutations in the MECP2 gene was a surprising finding considering the ubiquitous pattern of expression of MeCP2. However, MeCP2 is up-regulated in the brain and is believed to perform important
Scd 5 p Mediates Phosphoregulation of Actin and Endocytosis by the Type 1 Phosphatase Glc 7 p in Yeast

Pan1p plays essential roles in both actin and endocytosis in yeast. It interacts with, and regulates the function of, multiple endocytic proteins and actin assembly machinery. Phosphorylation of Pan1p by the kinase Prk1p down-regulates its activity, resulting in disassembly of the endocytic vesicle coat complex and termination of vesicle-associated actin polymerization. In this study, we focus on the mechanism that acts to release Pan1p from phosphorylation inhibition. We show that Pan1p is dephosphorylated by the phosphatase Glc7p, and the dephosphorylation is dependent on the Glc7p-targeting protein Scd5p, which itself is a phosphorylation target of Prk1p. Scd5p links Glc7p to Pan1p in two ways: directly by interacting with Pan1p and indirectly by interacting with the Pan1p-binding protein End3p. Depletion of Glc7p from the cells causes defects in cell growth, actin organization, and endocytosis, all of which can be partially suppressed by deletion of the PRK1 gene. These results suggest that Glc7p antagonizes the activity of the Prk1p kinase in regulating the functions of Pan1p and possibly other actinand endocytosis-related proteins.
Recovery following peripheral destruction of olfactory neurons in young and adult mice

Olfactory neurons (ON) which are located in the olfactory epithelium are responsible of odorous molecule detection. A unique feature of these cells is their continuous replacement throughout life due to the proliferation and differentiation of local neural precursors, the basal cells. Thus, experimental destruction of all ON induces a stimulation of basal cell division followed by tissue regeneration. The fact that ON precursors display such proliferative and neurogenic activity in adults makes these cells particularly attractive as a potential tool for nervous system repair. However, basal cell proliferation and, thus, ON production, decrease in relation to age; mostly during the first months of life. Therefore, we aimed to seek whether the ability of ON precursors to yield new functional ON in regenerative conditions was consequently impaired in adult. ZnSO4 intranasal perfusion administered to young (1 month) and adult (6 months) mice leads in a few days to total ON destruction and to hyposmia. Tissue and function restoration occurred in the following weeks in both mice groups and was preceded by a transient peak of cell division. In adults, although neurogenesis in the impaired olfactory epithelium was less efficient than in young mice, neural precursors retain their ability to provide new functional ON as indicated by the butanol detection recovery. This was achieved more rapidly than total ON regeneration, suggesting that a reduced number of reconnected ON may be sufficient for odor discrimination.
Problem Areas of the Rheumatic Mother

ABSTRACT: The extent to which women with rheumatic diseases are disabled in caring for their children is unknown. Fifty‐seven women with rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or systemic lupus erythematosus, all of whom had children under 6 years of age born during the disease, were interviewed. Patients with different diseases differed in their disabilities, but lifting, carrying, transporting, and bathing the child were difficult for most patients. Attention to these problem areas is necessary in the care of young mothers with rheumatic illness.
Probing the interaction of the multidrug-resistance phenotype with the polypeptide ionophore gramicidin D via functional channel formation.

It has been proposed that the multidrug resistance (MDR) transporter, P-glycoprotein (P-170), may be physiologically involved in the transport of polypeptides. As a step towards understanding the interaction of P-170 with polypeptides, we isolated various gramicidin-D-resistant mammalian cell lines. Gramicidin D is a hydrophobic pentadecapeptide ionophore that forms proton and alkali metal cation-permeable channels in lipid bilayers. Gramicidin-D-resistant cells displayed a prominent MDR gene amplification, P-170 overexpression, reduced drug accumulation, and consequent resistance to MDR-type cytotoxic agents. Modulators of the MDR phenotype, including verapamil, reserpine and quinidine, rendered these cells sensitive to gramicidin D. Using these cell lines, we established an assay that probes for the intra-membranal interaction between P-170 and gramicidin D. Gramicidin-D channel formation was followed by cellular accumulation of 86Rb+. Ionophore-resistant cells, and other MDR cells, did not show an appreciable increase in 86Rb+ influx rates, in the presence of increasing gramicidin-D concentrations. In contrast, parental cells displayed a dose-dependent increase in the 86Rb+ influx rates. Interestingly, in the absence of serum, gramicidin-D-resistant cells resumed the wild-type, ionophore-dose-dependent increase in 86Rb+ influx rates. MDR modulators caused a resumption of channel formation in ionophore-resistant cells. We conclude that acquisition of the MDR phenotype is an efficient means of cellular protection against gramicidin D. Hence, a new approach is offered in which P-170 interaction with gramicidin D is quantitatively followed by a rapid assessment of the biological activity (i.e. channel formation) of the substrate itself. Possible mechanisms of P-170 interaction with free ionophore monomers, and membrane-associated gramicidin D are discussed.
Review: Technical Aspects for the Utilization of Small Grain Straws as Feed Energy Sources for Ruminants: Emphasis on Beef Cattle

Wheat, oats, barley, rye, rice, and millet are all considered small grains. These small grains are carbohydrate and vitamin rich and have become food staples for humans and animals worldwide. Small grains have been cultivated by man for thousands of years and through selective breeding, they have become one of the most productive crops grown by man. Small grains have been adapted to grow in nearly every climate on earth. Rice and wheat are the largest crops in the world (Asseng, Foster, & Turner, 2011). Generally only seed portions of small grain plants are eaten by humans whereas non-seed parts of harvested small grain plants (straw) are largely considered waste.
Classifying Bad Chips and Ordering Test Sets

This paper shows data related to choosing a pair of test sets for digital IC production test. This data demonstrates that the choice of the second set of the pair should take into account the test metric used for the first test set. An approach for making this choice by taking defect coverage and total test length into account is presented
Validation of TIMI and GRACE acute coronary risk scores in Alexandria Governorate and their role in the comparison of quality of care between hospitals.

BACKGROUND Risk stratification in acute coronary syndrome (ACS) aims to identify those patients who might benefit prognostically from further investigation and treatment. In addition, risk stratification models have been used by health authorities and hospitals in quality management activities. AIM The present study aimed at validating the Thrombolysis In Myocardial Infarction (TIMI) and The Global Registry of Acute Coronary Events (GRACE) risk scores for prediction of mortality in patients with ACS in Alexandria governorate. In addition, the study aimed also at using one of the validated risk scores to compare risk adjusted mortality among participating hospitals. MATERIAL AND METHODS The study was conducted at hospitals belonging to 3 different health care organizations in Alexandria. All admitted patients with the diagnosis of ACS throughout a period of 6 months were included in the study (n=606). Discriminatory capacity and calibration of the TIMI and GRACE risk scores for detection of in-hospital mortality and mortality within six months of index admission were assessed. RESULTS The study showed that both TIMI and GRACE risk scores had high c statistics of 0.70 or higher. GRACE scores showed equal or higher c statistics than TIMI scores denoting better discriminatory capacity. TIMI risk score showed good calibration while GRACE risk score showed lower calibration capacity with certain patient categories. The GRACE risk score was used to calculate the standardized in-hospital mortality ratio which was higher than 1 for all participating hospitals indicating higher than expected mortality for ACS patients in these hospitals. CONCLUSIONS AND RECOMMENDATIONS GRACE risk score showed good discriminatory capacity, suggesting that it is suitable for clinical use among ACS patients in Alexandria governorate. It was recommended to use GRACE risk score for risk adjustment in quality management activities.
An interdisciplinary approach to the care of patients with Wegener's granulomatosis: long-term outcome in 155 patients.

OBJECTIVE To examine the outcome in 155 consecutive patients with Wegener's granulomatosis (WG) followed up for a median of 7 years. METHODS Treatment was adapted to the activity and extent of disease, with regular evaluation by an interdisciplinary team accompanied by group education about vasculitis. RESULTS The estimated median survival time was 21.7 years (95% confidence interval [95% CI] 15.60-27.86). Twenty-two patients died; 19 deaths were attributable to WG and/or its treatment. Significant predictors of survival at diagnosis were age >50 years (hazard ratio [HR] 5.45, 95% CI 1.97-15.02), kidney involvement with impaired renal function (HR 5.42, 95% CI 1.76-16.68), and lung involvement (HR 3.75, 95% CI 1.26-11.16). At some stage, 142 patients received prednisone and cyclophosphamide (CYC), usually as daily CYC plus mesna as uroprotection, 50 patients received trimethoprim/sulfamethoxazole, and 45 received methotrexate. Complete remission was achieved in 83 of the 155 patients. One or more relapses occurred in 99 patients after either complete or partial remission. CYC-induced cystitis and myelodysplastic syndrome occurred in 17 and 11 patients, respectively. A cumulative dose of 100 gm or more of CYC resulted in a 2-fold greater risk of CYC-related morbidity than with lower CYC doses. Serious infections occurred in 41 patients. CONCLUSION An interdisciplinary approach to the care of 155 WG patients resulted in a median survival of >21 years. Kidney or lung involvement at diagnosis was predictive of a >3-fold higher mortality. Although CYC remains essential in the treatment of WG, it was administered as briefly as possible and under close surveillance to avoid permanent CYC-related morbidity, which can lead to serious therapeutic problems in chronic relapsing WG.
Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism

Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling.
Measurement of cumulative physiological dysregulation in an older population

The allostatic load framework postulates that an important pathway connecting the social environment with health involves biological responses to stressful stimuli and the subsequent dysregulation of interrelated physiological systems. We formulate a new measure for cumulative physiological dysregulation using a grade of membership model estimated with biodemographic data from a national sample of older Taiwanese persons. We investigate associations between the measure and physical, psychological, and cognitive function. The results provide insights into the relationships between a set of biological profiles and various health outcomes, identify limitations of earlier approaches, and underscore next steps in the development of improved formulations of physiological dysregulation.
Compact space-like hypersurfaces with constant scalar curvature in locally symmetric Lorentz spaces

A new class of $(n+1)$-dimensional Lorentz spaces of index $1$ is introduced which satisfies some geometric conditions and can be regarded as a generalization of Lorentz space form. Then, the compact space-like hypersurface with constant scalar curvature of this spaces is investigated and a gap theorem for the hypersurface is obtained.
Beta-blocker under-use in COPD patients

Background Cardiovascular (CVS) comorbidities are common in COPD and contribute significantly to morbidity and mortality, especially following acute exacerbations of COPD (AECOPD). Beta-blockers (BBs) are safe and effective in COPD patients, with demonstrated survival benefit following myocardial infarction. We sought to determine if BBs are under-prescribed in patients hospitalized with AECOPD. We also sought to determine inpatient rates of CVS and cerebrovascular complications, and their impact on patient outcomes. Methods Retrospective hospital data was collected over a 12-month period. The medical records of all patients >40 years of age coded with a diagnosis of AECOPD were analyzed. Prevalent use and incident initiation of BBs were assessed. Comorbidities including indications and contraindications for BB use were analyzed. Results Of the 366 eligible patients, 156 patients (42.6%) had at least one indication for BB use – of these patients, only 53 (34.0%) were on BB therapy and 61 (39.1%) were not on BB therapy but had no listed contraindication. Prevalent use of BBs at the time of admission in all 366 patients was 19.7%, compared with 45.6%, 39.6% and 45.9% use of anti-platelets, statins and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, respectively. CVS and cerebrovascular complications were common in this population (57 patients, 16%) and were associated with longer length of stay (p<0.01) and greater inpatient mortality (p=0.02). Conclusions BBs are under-prescribed in COPD patients despite clear indication(s) for their use. Further work is required to explore barriers to BB prescribing in COPD patients.
Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa

Objective To assess the 24 month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission (MTCT) of HIV-1 in a breastfeeding population in West Africa. Methods Data were pooled from two clinical trials: DITRAME-ANRS049a conducted in Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina-Faso and RETRO-CI, conducted in Abidjan. Between September 1995 and February 1998, consenting HIV-1-seropositive women were randomly assigned to receive zidovudine (300 mg) or placebo: one tablet twice daily from 36–38 weeks’ gestation until delivery, then in DITRAME only, for 7 more days. Paediatric HIV-1 infection was defined as a positive HIV-1 polymerase chain reaction, or if aged ⩾ 15 months, a positive HIV-1 serology. Cumulative risks (CR) of infection were estimated using a competing risk approach with weaning as a competing event. Results Among 662 live-born children, 641 had at least one HIV-1 test. All but 12 children were breastfed. At 24 months, overall CR of MTCT were 0.225 in the zidovudine and 0.302 in the placebo group, a 26% significant reduction. Among children born to women with CD4 cell counts < 500/ml at enrolment, CR of MTCT were similar, 0.396 in the zidovudine and 0.413 in the placebo group. Among children born to women with CD4 cell counts ⩾ 500/ml, CR of MTCT were 0.091 in the zidovudine and 0.220 in the placebo group, a significant 59% reduction. Conclusion A maternal short-course zidovudine regimen reduces MTCT of HIV-1 at age 24 months, despite prolonged breastfeeding. However, efficacy was observed only among women with CD4 cell counts ⩾ 500/ml. New interventions should be considered to prevent MTCT, especially for African women with advanced HIV-1 immunodeficiency.
Traditional practices, traditional spirituality, and alcohol cessation among American Indians.

OBJECTIVE The detrimental effects of alcohol misuse and dependence are well documented as an important public-health issue among American Indian adults. This preponderance of problem-centered research, however, has eclipsed some important resilience factors associated with life course patterns of American Indian alcohol use. In this study, we investigate the influence of enculturation, and each of the three component dimensions (traditional practices, traditional spirituality, and cultural identity) to provide a stringent evaluation of the specific mechanisms through which traditional culture affects alcohol cessation among American Indians. METHOD These data were collected as part of a 3-year lagged sequential study currently underway on four American Indian reservations in the upper Midwest and five Canadian First Nation reserves. The sample consisted of 980 Native American adults, with 71% women and 29% men who are parents or guardians of youth ages 10-12 years old. Logistic regression was used to assess the unique contribution of the indicators of alcohol cessation. Excluding adults who had no lifetime alcohol use, the total sample size for present analysis is 732 adult respondents. RESULTS The findings show that older adults, women, and married adults were more likely to have quit using alcohol. When we examined the individual components of enculturation, two of the three components (participation in traditional activities and traditional spirituality) had significantly positive effects on alcohol cessation. CONCLUSIONS Although our findings provide empirical evidence that traditional practices and traditional spirituality play an important role in alcohol cessation, the data are cross-sectional and therefore do not indicate direction of effects. Longitudinal studies are warranted, in light of the work that concludes that cultural/spiritual issues may be more important in maintaining sobriety once it is established rather than initiating it.