Miracle-dz/UniFAR-FTUs huggingface dataset:
FTY720 produces caspase-independent cell death of acute lymphoblastic leukemia cells

Acute lymphoblastic leukemia (ALL), the most common form of childhood cancer, usually responds to chemotherapy but patients who develop disease relapse have a poor prognosis. New agents to treat ALL are urgently required. FTY720 is an immunosuppressive drug that has promising in vitro activity in a number of malignancies, with the proposed mechanism being the reactivation of the protein serine/threonine phosphatase, PP2A. FTY720 reduced the proliferation and viability of Ph+ and Ph- ALL cell lines and patient samples with IC50 values for viability between 5.3 to 7.9 μM. Cell death was caspase-independent with negligible activation of caspase-3 and no inhibition of FTY720-induced cell death by the caspase inhibitor Z-VAD-FMK. The cytotoxic effects of FTY720 were independent of PP2A reactivation as determined by the lack of effect of the PP2A inhibitor okadaic acid. Features of autophagy, including autophagosomes, LC3II expression and increased autophagic flux, were induced by FTY720. However the phosphorylated form of FTY720 (FTY720-P) similarly induced autophagy but not cell death. This suggests that autophagy is prosurvival in this setting, a finding supported by protection from cell death induced by the cytotoxic agent vincristine. FTY720 also induced reactive oxygen species (ROS) and the antioxidant N-acetyl-cysteine (NAC) partially reversed the cytotoxic effects, demonstrating a role for ROS generation in the cell death mechanism. FTY720 is an active drug in vitro in ALL cell lines and patient samples. Evidence supports a caspase-independent mechanism of cell death with the occurrence of autophagy and necrosis.
Smoking and caffeine and alcohol intake during pregnancy in a northern population: effect on fetal growth.

OBJECTIVES To assess the prevalence of smoking and of caffeine and alcohol intake during pregnancy in a northern population and to determine the relation of these factors to birth weight, length and head circumference. DESIGN Questionnaire survey and collection of maternal and newborn measurements. SETTING Ten communities in the Inuvik Zone, NWT. PATIENTS A total of 162 women (56 Inuit, 38 Indian, 37 white and 31 mixed race) who presented for prenatal care in their community and gave birth in Inuvik between September 1987 and January 1990 and their newborns. RESULTS In all, 64% (101/159) of the women smoked, 57% (88/154) ingested more than 300 mg of caffeine daily, and 34% (50/145) drank alcohol during their pregnancy. Smoking, caffeine intake and binge drinking were most frequent among the Inuit and Indian mothers. Smoking was significantly associated with decreased birth weight (p less than 0.001) and length (p less than 0.05). Alcohol intake, especially binge drinking, was significantly associated with decreased head circumference (p less than 0.05). Caffeine was found not to be related to any of the outcome variables after smoking was controlled for through stepwise multiple regression. CONCLUSIONS The marked prevalence of smoking and alcohol intake during pregnancy and their effects on the newborn are public health concerns in the Northwest Territories and warrant intensive countermeasures.
Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea

Abstract Objective: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn’s disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard. Methods: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed. Results: Diagnostic outcome: normal: n = 46 (73%), CC: n = 9 (14%), LC: n = 4 (6%), UC: n = 2 (3%), CD: n = 2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p = 0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups. Conclusion: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.
Size-resolved fluorescent biological aerosol particle concentrations and occupant emissions in a university classroom.

UNLABELLED This study is among the first to apply laser-induced fluorescence to characterize bioaerosols at high time and size resolution in an occupied, common-use indoor environment. Using an ultraviolet aerodynamic particle sizer, we characterized total and fluorescent biological aerosol particle (FBAP) levels (1-15 μm diameter) in a classroom, sampling with 5-min resolution continuously during eighteen occupied and eight unoccupied days distributed throughout a one-year period. A material-balance model was applied to quantify per-person FBAP emission rates as a function of particle size. Day-to-day and seasonal changes in FBAP number concentration (NF ) values in the classroom were small compared to the variability within a day that was attributable to variable levels of occupancy, occupant activities, and the operational state of the ventilation system. Occupancy conditions characteristic of lecture classes were associated with mean NF source strengths of 2 × 10(6) particles/h/person, and 9 × 10(4) particles per metabolic g CO2 . During transitions between lectures, occupant activity was more vigorous, and estimated mean, per-person NF emissions were 0.8 × 10(6) particles per transition. The observed classroom peak in FBAP size at 3-4 μm is similar to the peak in fluorescent and biological aerosols reported from several studies outdoors. PRACTICAL IMPLICATIONS Coarse particles that exhibit fluorescence at characteristic wavelengths are considered to be proxies for biological particles. Recently developed instruments permit their detection and sizing in real time. In a mechanically ventilated classroom, emissions from human occupants were a strong determinant of coarse-mode fluorescent biological aerosol particle (FBAP) levels. Human FBAP emission rates were significant under quiet occupancy conditions and increased with activity level. Fluorescent particle emissions peaked at a diameter of 3–4 μm, which is the expected modal size of airborne particles with associated microbes. Human activity patterns, and associated coarse FBAP and total particle levels varied strongly on short timescales. Thus, the dynamic temporal behavior of aerosol concentrations must be considered when determining collection protocols for samples meant to be representative of average concentrations using time-integrated or ‘snapshot’ bioaerosol measurement techniques.
Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes.

Silibinin, the main constituent of silymarin, a flavonoid drug from silybum marianum used in liver disease, was tested for inhibition of human cytochrome P-450 enzymes. Metabolic activities were determined in liver microsomes from two donors using selective substrates. With each substrate, incubations were carried out with and without silibinin (concentrations 3.7-300 microM) at 37 degrees in 0.1 M KH2PO4 buffer containing up to 3% DMSO. Metabolite concentrations were determined by HPLC or direct spectroscopy. First, silibinin IC50 values were determined for each substrate at respective K(M) concentrations. Silibinin had little effect (IC50>200 microM) on the metabolism of erythromycin (CYP3A4), chlorzoxazone (CYP2E1), S(+)-mephenytoin (CYP2C19), caffeine (CYP1A2) or coumarin (CYP2A6). A moderate effect was observed for high affinity dextromethorphan metabolism (CYP2D6) in one of the microsomes samples tested only (IC50=173 microM). Clear inhibition was found for denitronifedipine oxidation (CYP3A4; IC50=29 microM and 46 microM) and S(-)-warfarin 7-hydroxylation (CYP2C9; IC50=43 microM and 45 microM). When additional substrate concentrations were tested to assess enzyme kinetics, silibinin was a potent competitive inhibitor of dextromethorphan metabolism at the low affinity site, which is not CYP2D6 (Ki.c=2.3 microM and 2.4 microM). Inhibition was competitive for S(-)-warfarin 7-hydroxylation (Ki,c=18 microM and 19 microM) and mainly non-competitive for denitronifedipine oxidation (Ki,n=9 microM and 12 microM). With therapeutic silibinin peak plasma concentrations of 0.6 microM and biliary concentrations up to 200 microM, metabolic interactions with xenobiotics metabolised by CYP3A4 or CYP2C9 cannot be excluded.
Selective serotonin reuptake inhibitor-induced sexual dysfunction: efficacy of a drug holiday.

OBJECTIVE The purpose of this study was to evaluate whether weekend drug holidays would improve sexual functioning in recovered depressed patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. METHOD Thirty outpatients who reported worsening of sexual functioning during SSRI treatment were instructed to discontinue their SSRIs after the Thursday morning dose and to restart the SSRIs (at their previous dosage) on Sunday at 12:00 noon for four weekends. RESULTS Significant improvement in sexual functioning was reported by the patients taking sertraline and paroxetine but not by those taking fluoxetine. There were no statistically significant increases in mean Hamilton depression scores after discontinuation of the SSRIs; two patients had increases in scores from the 4-8 range to the 10-14 range. CONCLUSIONS For some patients taking sertraline and paroxetine who experience sexual dysfunction side effects, brief drug holidays may allow for significant improvement in sexual functioning without a significant return of depressive symptoms.
Emergency obstetrics care in a Nigerian tertiary hospital: a 20 year review of umblical cord prolapse.

CONTEXT Umbilical cord prolapse is an obstetric emergency associated with high perinatal morbidity and mortality unless prompt delivery by the fastest and safest route is carried out. OBJECTIVES To determine the incidence of umbilical cord prolapse, predisposing factors, and fetal outcome. STUDY DESIGN, SETTING AND SUBJECTS A 20 year retrospective study of all women who presented with umbilical cord prolapse at University of Maiduguri Teaching Hospital, Maiduguri, North-Eastern Nigeria. RESULTS During the study period there were 27,753 deliveries and 75 women had cord prolapse, giving the incidence of 1 in 370 deliveries (0.27%). Significantly more patients with non vertex presentation, twins and preterm delivery had cord prolapse. The highest occurrence was in those with unengaged presenting part (65.2%), spontaneous rupture of membrances (62.1%) and grandmultiparous women (57.6%). Caeserean section was carried out in 50% of cases, with mean decision-delivery interval of 77.1 +/- 21.7 minutes and 28/33 (84.9%) of babies delivered within 60 minute had normal Apgar scores. The Knee-chest position was most commonly used method of alleviating cord compression while arrangement for caesarean section was being made. The perinatal mortality was 27.3%. CONCLUSION umbilical cord prolapse is a brisk obstetric emergency with high perinatal morbidity and mortality unless prompt delivery is undertaken. Better communication and prompt response to emergency by the theatre team to reduce the decision-delivery interval would improve the perinatal outcome.
Clinical Utility of the Hopkins Competency Assessment Test on an Inpatient Geropsychiatry Unit

This study examined the clinical use of routine administration of the Hopkins Competency Assessment Test on an inpatient geropsychiatry unit. The purpose was to determine whether the Hopkins Competency Assessment Test results influenced the psychiatrist's capacity assessment or confidence in that determination. The test was administered to all patients admitted voluntarily during an 18-week period. The attending psychiatrist determined treatment consent capacity and rated confidence in that determination, before and after review of the test results. Fifty seven patients were assessed. After review of the test results, the psychiatrist's capacity rating changed in only 2 (3.5%) cases. However, the test increased the psychiatrist's confidence ratings, particularly among the patients with cognitive impairment. The Hopkins Competency Assessment Test is not suited for routine administration among geropsychiatry inpatients. However, the test may serve a role as a supplementary tool for assessing treatment consent capacity among patients with evidence of cognitive impairment.
A review of the affects of worry and generalized anxiety disorder upon cardiovascular health and coronary heart disease

Objective: The aims of this review article are to present psychophysiological and behavioral pathways for the involvement of worry and generalized anxiety disorder (GAD) upon cardiovascular function. The review will focus on persons with and without coronary heart disease (CHD), and encompass etiological and prognostic studies. Methods: Articles (1975–2011) reporting on GAD or worry affecting CHD prognosis or cardiovascular function were found using MEDLINE, EMBASE, SCOPUS and PsychINFO database searches, and extracted to form a narrative review. Results: Available evidence in experimental and observational studies in CHD free samples consistently showed that worry was associated with diminished heart rate variability (HRV) and elevated heart rate. Worry and GAD were commonly associated with blood pressure and diagnosed hypertension or medication use in both disease-free and established CHD populations. No evidence was found to support worry being beneficial to cardiovascular function or conducive to health promoting behaviors. The literature indicated that measures of worry were associated with fatal and nonfatal CHD in seven etiological studies of initially disease-free individuals; however, females were underrepresented. Three studies reported that GAD was associated with poorer prognosis in establish CHD, independent of depression. The median GAD prevalence was 10.4% in 3266 patients across 15 studies, suggesting that GAD is marginally less common in CHD samples than is depression. Conclusions: A growing literature highlights the association between worry and development of CHD. The association between worry, GAD and CHD risk factors (e.g. blood pressure), and HRV are leading mechanisms of cardiopathogenesis that may affect cardiovascular function. Findings regarding worry and GAD in established CHD are less clear.
Allium TM Bulbar Urethral Stent: An Updated Long-Term Multi-Center Study with New Treatment Modality for Bulbar Urethral Stricture

Objectives: To report the 2-years follow-up of patients with bulbar urethral strictures treated with the new AlliumTM Bulbar Urethral Stent (Allium BUS). Methods: The stent is a fully covered, self-expendable, large caliber metal stent specially designed for the treatment of bulbar urethral strictures. The stent is comprised of a coiled super-elastic structure covered by a polymeric coating designed to prevent mucosal hyperplasia. The indwelling time is 12 months, after which the stent should have been removed. Sixty-four patients with recurrent bulbar stricture were treated with Allium BUS in 3 worldwide centers. Results: All stents were successfully inserted with no perioperative complications. In a median follow-up of 25.5 months, the mean maximal flow rate following stent insertion was significantly higher compared to the pre-surgical flow rate (14 ml/sec vs 6.6 ml/sec, p < 0.0001). Longer indwelling time and shorter stricture length were significantly related to success rate. The main complications were stent migration, stent re-stenosis and urinary tract infections. Conclusions: The temporary placement of the AlliumTM BUS showed encouraging results with long-term failure rate of only 25%.
Dynamics of subduction initiation at preexisting fault zones

We show that a new subduction zone can initiate at a preexisting dipping fault zone with reasonable plate forces, consistent with what is observed in the western Pacific. The dynamics of subduction initiation within a viscoelastic medium has been systematically explored with the finite element method. We investigate the compression of oceanic lithosphere with both force and velocity boundary conditions and track the thermal structure in which heat is transported by both advection and diffusion. The viscosity of the medium is non-Newtonian and temperature-dependent. We also examine the influence of a perfectly plastic yield stress. A new method to model the preexisting weak zone as a graded fault with remeshing is introduced. The first 400 km of plate convergence is examined during which time there are profound changes in plate boundary dynamics. Initially, topography across the plate boundary is characterized by over 1000 m of uplift close to the trench. Subsequently, a bathymetric depression develops on the overriding plate with an initial subsidence rate of 125 m/Myr for a slab subducting at 2 cm/yr. Tectonic subsidence of the overriding plate is primarily dependent upon the depth of slab penetration. For a plate force of 4×10^(12) N/m, subduction initiates even with a fault shear stress of 3 MPa, the resistance most consistent with seismological observations. However, subduction will not initiate when this fault shear stress is >5 MPa. Our results are consistent with plate reconstructions, which predict the initiation of subduction across preexisting weak zones within oceanic basins.
Intestinal drug absorption and metabolism. 3. Glycine conjugation and accumulation of benzoic acid in rat intestinal tissue.

Glycine conjugation of 14C-benzoic acid to 14C-hippuric acid was demonstrated in in vitro rat intestinal slices and everted intestinal preparations. Hippuric acid was detected and quantified by two independent analytical techniques, a quantitative TLC method, and a reverse isotope dilution method. Comparison of hippuric acid concentration after 2 hr. in mucosal and serosal fluids when hippuric acid was formed endogenously from benzoic acid, and with mucosal and serosal concentrations when hippuric acid was added exogenously to the mucosal fluid, indicated that hippuric acid is formed in the tissue compartment rather than by bacterial or intestinal enzymes in the mucosal fluid. Hippuric acid is apparently formed enzymatically in the mucosal cell according to a previously proposed cell compartment model and subsequently diffuses to both mucosal and serosal fluids. The net amount of hippuric acid formed under the conditions of the study was small (about 1%) and was found to be due to limited synthesis rather than to extensive hydrolysis. Both exogenously added benzoic acid and hippuric acid accumulated in the intestinal tissue compartment (11.2 and 6.4%, respectively) during transfer from the mucosal fluid.
OVERVIEW OF NORRIS & ORTEGA ’ S ( 2000 ) META-ANALYSIS

Since Norris and Ortega‟s (2000) seminal work on the effectiveness of second language instruction, there has been a proliferation of meta-analyses in the field of applied linguistics. Subsequent meta-analysts, however, have uncritically followed the methodological choices made by Norris and Ortega. This paper suggests a critical reevaluation of the methodological procedures underlying the Norris and Ortega (2000) meta-analysis. I reexamined their procedures, and reassessed the 49 unique samples they used in their meta-analysis. In doing so, I identified three key methodological limitations with the study, pertaining, respectively, to (a) the data collection procedure, (b) the coding system, and (c) the statistical analysis. I argue that the lack of data quality inherent in the primary studies, the oversimplified coding scheme, and the inappropriate use of effect size statistics combine to compromise the validity of the conclusions Norris and Ortega have drawn from their meta-analysis. I subsequently provide alternative procedures which may yield a more empirically sound research synthesis, recommending, for future meta-analysts, the „best evidence synthesis‟ approach where conclusions are drawn from combining quantitative and qualitative analyses.
Abandoning negative marking.

The European Diploma of Anesthesiology and Intensive Care was created in 1984. It has matured and developed over the last 24 yr into a multilingual examination, which takes place today in more than 20 centres in Europe. It consists of two parts – Part 1 (the primary examination) and Part 2 (the final examination). The primary examination takes place in the form of a written multiple-choice examination. The ‘True/ False/ Don’t Know’ format is used, where every candidate can mark one of three boxes on the computerreadable mark sheet corresponding to one of these three decisions. If none of the three boxes are marked for an individual question, the choice of ‘Don’t Know’ is assumed. The number of correct responses is counted and each is given a score of 11. Likewise, each incorrect response is given a score of 21. A response of ‘Don’t Know’ receives a score of 0. Subtracting the number of incorrect responses from the number of correct responses gives the candidate’s score. Until 1969, in the UK, the Part I of the Membership Examination of the Royal College of Physicians was scored by the above method (11, 21 and 0) described by the Study Group of The London College in 1967 and modified in 1969 [1]. This method was called Formula Scoring, defined by the formula
Long-term wheel-running and acute 6-h advances alter glucose tolerance and insulin levels in TALLYHO/JngJ mice

ABSTRACT Studies have shown a relationship between circadian rhythm disruptions and type-2 diabetes. This investigation examined the effects of circadian disruption (6-h phase advances) on the progression of diabetes in a type-2 diabetic mouse model –TALLYHO/JngJ – and whether wheel-running can alleviate the effects of the phase advances. 6-h advances alter fasting glucose, glucose tolerance and insulin production. Wheel-running reduced body mass, improved glucose tolerance and reduced insulin in TALLYHO/JngJ and alleviated some of the changes in diabetic symptoms due to 6-h advances. These results indicate that individuals with type-2 diabetes can benefit from physical activity and exercise can be a countermeasure to offset the effects of an acute phase advance.
Density Determination of a Small Isotopically Enriched Silicon Single Crystal

For a new determination of the Avogadro constant using small crystals of isotopically enriched silicon, the density of a sample was determined at Physikalisch-Technische Bundesanstalt. The sample has a mass of 58 g and a 28Si enrichment of about 99.98%. Its density was compared by the pressure-of-flotation method to the density of a large hollow transfer standard that was manufactured from natural silicon, to have the same density. The flotation measurement yielded a relative density difference of 0.64(10) 10-6. The density of the transfer standard was then measured by hydrostatic weighing, which is traceable to a primary density standard. Thus, the density of the small 28Si sample was determined to be 2320.08031(40) kg/m 3, i.e., with a relative standard uncertainty of 0.17 10-6