Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug Therapy in Schizophrenia — Variability of Outcome and Prediction of Response*

In spite of the proven benefits of neuroleptics in reducing acute psychotic symptoms and in preventing relapse in schizophrenic patients, not all schizophrenics benefit equally from neuroleptic therapy. Predictors of response include: demographics, clinical characteristics, neurologic soft signs, neurocognitive functioning, morphologic brain changes, drug blood levels, indices of blockade of the dopamine receptors, subjective response to medications as well as early symptomatic improvement. Methodological difficulties in outcome research in drug therapy are reviewed. No single factor has been identified as a reliable predictor of drug response, and it is unlikely that such a single predictor will prove useful in a heterogeneous illness such as schizophrenia. This paper reviews the factors, which have been suggested as useful in developing better understanding of variability of drug response among schizophrenics.
Novel Cell-Based Hepatitis C Virus Infection Assay for Quantitative High-Throughput Screening of Anti-Hepatitis C Virus Compounds

ABSTRACT Therapy for hepatitis C virus (HCV) infection has advanced with the recent approval of direct-acting antivirals in combination with peginterferon and ribavirin. New antivirals with novel targets are still needed to further improve the treatment of hepatitis C. Previously reported screening methods for HCV inhibitors either are limited to a virus-specific function or apply a screening method at a single dose, which usually leads to high false-positive or -negative rates. We developed a quantitative high-throughput screening (qHTS) assay platform with a cell-based HCV infection system. This highly sensitive assay can be miniaturized to a 1,536-well format for screening of large chemical libraries. All candidates are screened over a 7-concentration dose range to give EC50s (compound concentrations at 50% efficacy) and dose-response curves. Using this assay format, we screened a library of pharmacologically active compounds (LOPAC). Based on the profile of dose-dependent curves of HCV inhibition and cytotoxicity, 22 compounds with adequate curves and EC50s of <10 μM were selected for validation. In two additional independent assays, 17 of them demonstrated specific inhibition of HCV infection. Ten potential candidates with efficacies of >70% and CC50s (compound concentrations at 50% cytotoxicity) of <30 μM from these validated hits were characterized for their target stages in the HCV replication cycle. In this screen, we identified both known and novel hits with diverse structural and functional features targeting various stages of the HCV replication cycle. The pilot screen demonstrates that this assay system is highly robust and effective in identifying novel HCV inhibitors and that it can be readily applied to large-scale screening of small-molecule libraries.
Candesartan prevents L-NAME-induced cardio-renal injury in spontaneously hypertensive rats beyond hypotensive effects

Our goal was to assess the cardiovascular and renal protection afforded by angiotensin II type 1-receptor blockade against NG-nitro-L-arginine methyl ester (L-NAME)-exacerbated hypertension in young spontaneously hypertensive rats (SHR), in comparison with the antihypertensive drug, hydralazine. Male SHR were assigned to four groups (n=8 per group): no treatment (controls); L-NAME-treated group (20 mg/kg/day, 10 days, orally); co-treatment with L-NAME and hydralazine (15 mg/kg/day, by gavage); co-treatment with L-NAME and candesartan cilexetil (10 mg/kg/day, by gavage), i.e. at a dose that inhibited acute pressor responses to 5—20 ng angiotensin II. One animal died in the L-NAME group, and tail-cuff systolic blood pressure (SBP) increased significantly compared with controls to 201±5 mmHg. Albumin excretion increased 235-fold in L-NAME-treated rats. Heart weight index averaged 3.5±0.1 and 3.8±0.1 mg/g body weight (p<0.05) in control and L-NAME rats, respectively, indicating moderate cardiac hypertrophy induced by L-NAME. Preglomerular vascular lesions affected 63±6% of interlobular arteries and 10±2% of afferent arterioles (vs. 8±3 and 0.8±0.4% in controls, respectively). Hydralazine and candesartan cilexetil treatment similarly reduced SBP to 153±7, and 165±6 mmHg, respectively. However, candesartan provided more protection, in terms of no significant change in albuminuria (vs. 25-fold increase with hydralazine), regression of cardiac hypertrophy, frequency of vascular lesions and histological indices of renal injury maintained within control values. In conclusion, candesartan cilexetil prevented L-NAME-exacerbated hypertension and associated cardio-renal injury in young SHR, the beneficial effects exceeding those of hydralazine.
Nitric Oxide Attenuates but Superoxide Enhances iNOS Expression in Endotox in‐ and IFNγ‐Stimulated Skeletal Muscle Endothelial Cells

Objective: Endothelial cells (ECs) in septic skeletal muscle may be exposed to large amounts of NO and superoxide generated by the skeletal muscle cells. We tested the hypothesis that inducible nitric oxide synthase (iNOS) induction in ECs (i.e., one of the steps in the septic process) is modulated by extravascularly generated nitric oxide (NO) and superoxide.
Neutron-Induced Upsets in NAND Floating Gate Memories

We investigate atmospheric neutron effects on floating-gate cells in NAND Flash memory devices. Charge loss is shown to occur, particularly at the highest program levels, causing raw bit errors in multilevel cell NAND, but to an extent that does not challenge current mandatory error correction specifications. We discuss the physical mechanisms and analyze scaling trends, which show a rapid increase in sensitivity for decreasing feature size.
Cupping Glass

The art of cupping is ancient dating back to both the Romans and the Greeks. Cups removed from archaeologic excavations were made of both metal and glass. The object of cupping was to increase the circulation in a specific area by placing the air-exhausted glass cup over the skin. Several methods to create a vacuum with negative pressure in the cupping glass were used. The most common procedure was to heat the air within the glass and apply the cup as the air cooled, but before the partial vacuum was lost. Air was exhausted from the cup by warming it over a flame or by lighting a piece of gauze or paper in the cup to create the vacuum. The burning material was discarded and the cup rapidly applied to the skin to draw blood to the surface. Another, less practiced technique was to apply a brass syringe to a hole in the dome of the cup to produce the suction. The heated glass was the method most favored. Dry cupping was a procedure where the skin remains intact; wet cupping results in the actual removal of blood. This was accomplished by first incising the skin with a multibladed instrument called a scarifier. Bleeding was thought to remove “corrupt” blood and was a commonly practiced therapy for two millennia. The Latin word “curcurbita” meaning gourd or in the shape of a gourd was used as a synonym for cupping. Cups made from the hollow portion of an animal horn were called cupping horns. Such devices were described by Ambroise Pare, the famous sixteenth century French surgeon. Typical glass cups were made of a good quality flint glass with a rolled rim that ensured even tight application to the skin to preserve the vacuum. Cupping glasses from the eighteenth and nineteenth century were often found in a set of three with a brass scarifier in velvet-lined rosewood cases. The typical practitioner of this art would carry such a set or perhaps just a few loose glass cups. Illustrated is a typical glass cup which had the thin applied rolled edge. The usual cup size ranged from 1 2 to 2 inches in diameter. This one is 1 4 inches in diameter and 2 1 2 inches in height. It was hand blown as noted by the typical flat pontil on the dome and dates from the mid-nineteenth century.
Validity of a Repeated-Sprint Test for Football

Three studies involving 108 football players were conducted to examine the reliability of a repeated-shuttle-sprint ability (RSSA) test and its ability to differentiate between players of various competitive levels and playing positions. Study 1: Short-term reliability was determined in 22 professional players completing the RSSA test (6 x 40-m sprints with 20 s of recovery between sprints) on two separate occasions. Study 2: Long-term reliability (seasonal changes) was examined in 31 professional players completing the RSSA test four times (during the preseason period, at the start, middle and end of the competitive season). Study 3: 108 players were divided and compared according to competitive level or playing position. Standard error of measurement values expressed as coefficient of variation for RSSA mean time and best time were 0.8 and 1.3 % (short-term reliability) and 0.9 and 1.2 % (long-term reliability), respectively. The smallest worthwhile changes were 0.5 % for both mean and best time. Professional players showed better RSSA performance than amateur players, and defenders displayed the lowest RSSA performance. In conclusion, the RSSA test showed adequate construct validity but only RSSA mean time showed sufficient reliability to detect large training-induced changes but not small important differences.
Arg16 homozygosity of the beta2-adrenergic receptor improves the outcome after beta2-agonist tocolysis for preterm labor.

BACKGROUND Beta(2)-adrenergic receptor (beta(2)AR) agonists are not consistently successful when administered as tocolytic therapy. The beta(2)AR displays genetic variability; an arginine-to-glycine substitution at codon 16 (Arg16Gly) has been shown to increase receptor desensitization in response to agonist exposure, whereas a substitution of glutamate for glutamine at codon 27 (Gln27Glu) decreases down-regulation. We have demonstrated that homozygosity for Arg16 protects against preterm delivery. Our goal was to determine whether beta(2)-agonists are more effective in women with the Arg16 genotype and preterm labor. METHODS Sixty white women with preterm labor between 24 and 34 weeks' gestation were treated for 48 hours with intravenous hexoprenaline. The effect of tocolysis and outcome of pregnancy were recorded. The beta(2)AR genotypes at codons 16 and 27 of ADRB2 were determined. A control group of 116 women delivered at term was also genotyped. RESULTS Preterm labor was not associated with beta(2)AR genotype at codon 16 (17% of patients with preterm labor were Arg16 homozygotes versus 19% of control subjects) or codon 27. Gestation was significantly prolonged in Arg16 homozygotes (median, 69 days; interquartile range, 63-79 days) compared with the other 2 genotypes (median, 58 days; interquartile range, 2-72 days) (P = .04). Tocolysis was 100% successful in delaying delivery for 48 hours in Arg16 homozygotes (n = 10), just failing to achieve statistical significance (P = .069). In contrast, only 37 of 50 women carrying 1 or 2 glycine alleles (74%) had delivery delayed by more than 48 hours with tocolysis. Neonatal outcomes were significantly better in babies born to mothers homozygous for arginine than in women with 1 or 2 Gly16 alleles. CONCLUSIONS This is the first study examining the pharmacogenetics of beta(2)AR agonist therapy for preterm labor. It appears that Arg16 homozygosity improves pregnancy outcome after beta(2)-agonist tocolysis. The relatively low frequency of Arg16 homozygotes in our population limited the power of this investigation. Future assessments of tocolytic therapy may need to assess beta(2)AR genotype.
The Use of TLM and Kriging Methods for Electromagnetic Compatibility Management in Health Care Facilities

This paper promotes the use of numerical methods as an alternative tool in order to evaluate and manage electromagnetic compatibility in health care facilities. Numerical analysis is performed employing the transmission line modeling (TLM) method and kriging, which are supported by measurement tests, providing a reliable assessment of the electromagnetic profile established in clinical environments.
Religiosity, Magical Ideation, and Paranormal Beliefs in Anxiety Disorders and Obsessive-Compulsive Disorder: A Cross-Sectional Study

Abstract The relation between religiosity/spirituality (R/S), personal beliefs, and mental health has been extensively studied. However, concerning anxiety disorders (ADs), empirical evidence is scarce. This study investigated the differences in R/S and magical/paranormal ideation among obsessive-compulsive disorder patients (OCD; n = 49), patients with other ADs (n = 36), and healthy controls (HCs; n = 35). Our results suggest negative religious coping as being the only parameter showing significantly higher scores in OCD and AD participants in comparison with HCs. Negative religious coping reflects negative functional expressions of R/S in stressful situations. Logistic regression also suggested negative religious coping as the strongest predictor of group affiliation to the nonhealthy group. Further results show no significant differences between other R/S, magical, and paranormal ideation traits among groups. This study underlines an important role of negative religious coping in ADs yet does not clearly indicate a specific causality. Religious-sensitive treatment targeting cognitive aspects of negative religious coping are discussed.
RELEASE AND EXCHANGE STUDIES RELATING TO THE SYNAPTOSOMAL UPTAKE OF GABA

Abstract— Synaptosomal release and exchange of [3H]GABA were studied by a superfusion technique which minimizes reuptake. The release of [3H]GABA was increased by depolarizing concentrations of KCl and showed calcium‐dependence. Superfusion with 1‐1000 μm unlabelled GABA caused a dose dependent, saturable increase in the release of radioactivity by homoexchange. The exchange process showed high substrate specificity: among the various amino acids and putative neurotransmitters tested, only γ‐amino‐β‐hydroxybutyric acid was a good stimulator of [3H]GABA release. Superfusion with sodium‐free medium (NaCl replaced by sucrose) virtually abolished homoexchange. Ouabain also increased the release of [3H]GABA, and its action was additive to that of unlabelled GABA.
Growth Factors , Cytokines , Cell Cycle Molecules The Methylation of the TSC 2 Promoter Underlies the Abnormal Growth of TSC 2 Angiomyolipoma-Derived Smooth Muscle Cells

From the Laboratory of Pharmacology,* the Medical Genetic Unit, the Division of Pathology, the Disabled Advanced Medical Assistance Unit, and the Urology Unit, Department of Medicine, Surgery, and Dentistry, Polo H. San Paolo, Faculty of Medicine and Surgery, University of Milan, Milan; Clinical Pharmacology, Istituti di Ricovero e Cura a Carattere Scientifico Humanitas, Milan; Fondazione Istituti de Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico,** Mangiagalli and Regina Elena, Milan, Italy
Influence of reproductive stage upon the fertility of gonadotrophin-treated female rabbits.

Gonadotrophic preparations have been used experimentally to bring about the ovulation of fertilizable ova in mice (Engle, 1927) rats (Cole, 1937; Evans and Simpson, 1940) and rabbits (Pincus, 1940). No adequate estimates have been made, however, of the initial fertility of the eggs in these species. In some larger animals, there is the suggestion that the fertility of the eggs is affected by the stage of the reproductive cycle at the time of treatment. Cows treated in the early part of the estrous cycle yielded no fertilized eggs (Zavadovskii et al. 1935; Casida et al. 1940; Casida et al. 1943). but good fertility was obtained by the latter workers in those treated late in the cycle. Fertility has also been obtained in sheep treated in the follicular phase of the estrous cycle (Loginova and Lopyrin, 1938; Parkes and Hammond, 1940; Hammond et al. 1942).
Peroxisome proliferator‐activated receptor γ agonists potentiate the cytotoxic effect of valproic acid in multiple myeloma cells

The main challenge in using chemotherapy to treat multiple myeloma (MM) is drug resistance. In order to evaluate the anti‐neoplastic properties of a new drug combination in MM, two clinically available drugs, valproic acid (VPA) a histone deacetylase (HDAC) inhibitor and pioglitazone, a peroxisome proliferator‐activated receptor gamma (PPARγ) agonist, were tested in vitro on MM cell lines and MM patient cells. The sensitivity towards VPA alone was observed on several MM cell lines tested and also on primary myeloma cells and peripheral blood mononuclear cells from healthy donors. Importantly, the addition of a PPARγ agonist to the VPA treatment increased the cytotoxic effect of VPA in a synergistic/additive manner on the different MM cell lines and MM patient cells. This effect was observed at the physiological range of VPA used to treat epileptic patients. The mechanisms underlying this increase induced a cell cycle arrest and caspase‐dependent apoptosis. The potentiation of the effect of VPA by pioglitazone was mediated by higher acetylation levels of histones H3 and H4 compared to levels induced by HDAC inhibitors alone. This association reveals a new promising chemotherapeutic combination to be tested in MM.
A Deficit in Older Adults' Effortful Selection of Cued Responses

J. J. Adam et al. (1998) provided evidence for an "age-related deficit in preparing 2 fingers on 2 hands, but not on 1 hand" (p. 870). Instead of having an anatomical basis, the deficit could result from the effortful processing required for individuals to select cued subsets of responses that do not coincide with left and right subgroups. The deficit also could involve either the ultimate benefit that can be attained or the time required to attain that benefit. The authors report 3 experiments (N s = 40, 48, and 32 participants, respectively) in which they tested those distinctions by using an overlapped hand placement (participants alternated the index and middle fingers of the hands), a normal hand placement, and longer precuing intervals than were used in previous studies. The older adults were able to achieve the full precuing benefit shown by younger adults but required longer to achieve the maximal benefit for most pairs of responses. The deficit did not depend on whether the responses were from different hands, suggesting that it lies primarily in the effortful processing required for those subsets of cued responses that are not selected easily.
The Effect of Training Status on the Serum Creatine Kinase Response, Soreness and Muscle Function Following Resistance Exercise

Untrained individuals develop muscle soreness and increased serum creatine kinase (CK) activity in the blood after strenuous, unaccustomed exercise. An unpublished observation in our laboratory revealed that trained weightlifters also experience considerable soreness after unaccustomed exercise, but may not show a dramatic CK response. This study examined the CK and soreness responses to strenuous exercise in weightlifters (TR, n = 10) and untrained subjects (UTR, n = 10). Trained subjects had a minimum of three years weightlifting experience, and regularly performed squats and leg presses. Untrained subjects had not participated in any regular resistance exercise for the past three years. Following two acclimation sessions, subjects reported to the lab on seven consecutive days and on the tenth day after knee extensor exercise. Weight training sessions occurred on day 1 for the knee extensors (KE) and day 2 for the knee flexors (KF). The weight training consisted of these exercises (sets): squat (5), leg press (3), leg extension and lunge (3) for the KE, double leg curls (6), single leg curls (3), stiff-legged deadlifts (4, TR group only) for the KF at 12 RM for all exercises. To document the stress due to exercise, the loss in strength (isometric peak torque, IPT) was assessed on a Biodex isokinetic dynamometer. Maximal voluntary IPT of the KE at 90 degrees and the KF at 80 degrees decreased 17-30% with no significant differences between groups. Muscle soreness during simulated squat leg curl movement was assessed by a 100 mm visual analog scale (VAS). Average peak KE soreness was 76 mm for TR and 58 mm for UTR, KF soreness was 60 mm for TR and 47 mm for UTR post-exercise. Serum CK levels were significantly different between groups with a peak of 1349 IU for TR and 3272 IU for the UTR (p < 0.01). Although the TR group experienced greater soreness than the UTR, peak serum CK activity was significantly lower, suggesting that trained individuals can develop severe soreness without the same degree of increase in serum CK activity observed in untrained individuals.
Left ventricular filling in arterial hypertension. Influence of obesity and hemodynamic and structural confounders.

We assessed the relations of left ventricular filling to load and geometry by Doppler echocardiography in 80 normotensive subjects (40 normal-weight [36 +/- 12 years, 24 women] and 40 obese [35 +/- 13 years, 24 women]) and 61 hypertensive subjects without silent coronary heart disease (29 normal-weight [43 +/- 13 years, 15 women] and 32 obese [42 +/- 13 years, 19 women]) and comparable left ventricular midwall performance. Left ventricular mass divided by height to the 2.7 power was higher in all groups than in normotensive normal-weight subjects (all P < .0001) and in hypertensive than normotensive obese subjects (P < .001). After controlling for age, sex, blood pressure, and heart rate, isovolumic relaxation time was prolonged in hypertensive subjects and normotensive obese subjects compared with normotensive normal-weight subjects (all P < .0001). Body mass index, left ventricular dimension and mass, and circumferential end-systolic stress did not influence these differences. In pooled groups, prolonged isovolumic relaxation time was predicted by high mean blood pressure (beta = 0.52, P < .001), low end-systolic stress (beta = -0.33, P < .001), increased left ventricular mass (beta = 0.24, P < .004), and high body mass index (beta = 0.14, P < .05, multiple R = .72, SEE = 16.5 milliseconds, P < .0001). Between-group differences in peak early transmitral flow velocity, the deceleration time of early filling velocity, and the ratio of early to late left ventricular filling disappeared after controlling for left ventricular mass. Thus, (1) isovolumic relaxation time is prolonged in both arterial hypertension and obesity; (2) the presence of obesity does not significantly increase isovolumic relaxation time in hypertension; and (3) abnormalities of left ventricular filling in arterial hypertension are offset after controlling for left ventricular mass.
Les substrats cérébraux du déclin de la mémoire sémantique dans le vieillissement pathologique : contributions de la magnétoencéphalographie

iii Table des matières . v Liste des tableaux . vii Liste des figures . viii Liste des abréviations . ix Remerciements. xi CHAPITRE 1 : INTRODUCTION GÉNÉRALE . 1 1.1 Mémoire sémantique . 2 1.2 Architecture cognitive et cérébrale de la MS . 4 1.3 Processus dynamiques du traitement sémantique : la N400 . 9 1.4 Mémoire sémantique et vieillissement normal . 11 1.5 Mémoire sémantique et vieillissement pathologique . 12 1.5. 1 Les démences . 12 1.5. 2 La maladie d’Alzheimer . 12 1.5. 3 Les troubles sémantiques dans la MA. 14 1.5. 4 Le Trouble cognitif léger. 15 1.5. 5 Les troubles sémantiques dans le TCLa. 19 1.5. 6 Les bases cérébrales des atteintes sémantiques dans le TCLa . 20 1.5. 7 Le variant sémantique de l’aphasie primaire progressive. 22 1.5. 8 Les bases cérébrales du déclin sémantique dans l’APPvs . 25 1.6 Réorganisation cérébrale, compensation et MS . 26 1.7 Position du problème, objectifs et structure de la thèse . 32