Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies

Objective: Patients with hematologic malignancies are at substantial risk of developing invasive fungal infections (IFI) that are associated with substantial morbidity and mortality. This article reviews the epidemiology, risk factors, and efficacy of antifungal prophylaxis in patients with hematologic malignancies. Methods: A PubMed search was conducted to identify relevant studies with special emphasis on meta‐analyses and direct comparisons between antifungal agents. Results: The epidemiology of IFI has changed substantially in recent years with Candida albicans becoming less common owing to the widespread prophylactic use of azole antifungals. Invasive aspergillosis, fusariosis, and zygomycosis have increased in frequency. This change is at least partly related to the use of broad‐spectrum antifungal agents, either as prophylaxis or as empirical treatment. Other risk factors for IFI include prior fungal exposure, immunosuppression, underlying disease, graft‐vs.‐host disease, and organ dysfunction. Inconsistent results have been reported in studies evaluating the efficacy of antifungal prophylaxis in patients at risk of IFI. Meta‐analyses found that antifungals, such as fluconazole and itraconazole, are effective in decreasing IFI and IFI‐related mortality, primarily owing to yeast infections in patients with more severe immunosuppression (i.e. patients undergoing bone marrow transplantation), but do not decrease the overall mortality. The European Conference on Infections in Leukemia (ECIL) guidelines currently recommend fluconazole (AI, ie. strongly recommended, based on at least 1 well‐executed, randomized trial) and itraconazole (BI, ie. generally recommended, based on at least 1 well‐executed, randomized trial) in allogeneic transplant recipients. Posaconazole, a triazole antifungal, has been recently shown to decrease IFI incidence and overall mortality in some high‐risk patients compared with standard azoles. Based on preliminary data, a provisional AI ECIL recommendation has been given. Conclusions: Because of the substantial morbidity and mortality associated with IFI, there is a need to accurately define patient groups at greatest risk of IFI and, when appropriate, to initiate effective antifungal prophylaxis.
The effect of metoclopramide on gastroduodenal and gallbladder contractions

The effect of metoclopramide on gastroduodenal and gallbladder contractions in the dog has been studied. It increased the strength of antral contractions and produced stronger, more regular, duodenal contractions; these tended to follow those of the antrum, providing evidence of the dominance of antral contraction rate over that of the duodenum. In the absence of spontaneous antral activity, there was little effect on either stomach or duodenum and this was not related to the type of anaesthetic used. There was no effect on the gallbladder when it was relaxed or submaximally stimulated with cholecystokinin/pancreozymin. Further evidence has been obtained that metoclopramide acts by enhancing the local effect of acetylcholine on gastric smooth muscle. These findings provide a satisfactory mechanism for most of the observed clinical effects.
Dysregulation of the Polo-Like Kinase Pathway in CD4+ T Cells Is Characteristic of Pathogenic Simian Immunodeficiency Virus Infection

ABSTRACT CD4+ T-cell dysfunction highlighted by defects within the intracellular signaling cascade and cell cycle has long been characterized as a direct and/or indirect consequence of human immunodeficiency virus (HIV) infection in humans and simian immunodeficiency virus (SIV) infection in rhesus macaques (RM). Dysregulation of the M phase of the cell cycle is a well-documented effect of HIV or SIV infection both in vivo and in vitro. In this study the effect of SIV infection on the modulation of two important regulators of the M phase—polo-like kinases Plk3 and Plk1—was investigated. We have previously shown that Plk3 is markedly downregulated in CD4+ T cells from SIV-infected disease-susceptible RM but not SIV-infected disease-resistant sooty mangabeys (SM), denoting an association of downregulation with disease progression. Here we show that, in addition to the downregulation, Plk3 exhibits aberrant activation patterns in the CD4+ T cells from SIV-infected RM following T-cell receptor stimulation. Interestingly, in vitro SIV infection of CD4+ T cells leads to the upregulation, rather than downregulation, of Plk3, suggesting that different mechanisms operate in vitro and in vivo. In addition, CD4+ T cells from RM with high viral loads exhibited consistent and significant upregulation of Plk1, concurrent with an aberrant activation-induced Plk1 response, suggesting complex mechanisms of SIV-induced M-phase abnormalities in vivo. Altogether this study presents a novel mechanism underlying M-phase defects observed in CD4+ T cells from HIV or SIV-infected disease-susceptible humans and RM which may contribute to aberrant T-cell responses and disease pathogenesis.
The role of education in mini-mental state examination: a study in Northeast Brazil.

BACKGROUND There is evidence that schooling can influence performance in cognitive assessment tests. In developing countries, formal education is limited for most people. The use of tests such as Mini-Mental State Examination (MMSE), could have an adverse effect on the evaluation of illiterate and low education individuals. OBJECTIVE To propose a new version of MMSE as a screening test to assess Illiterate and low education people. METHOD A study was carried out enrolling 232 individuals, aged 60 or more of low and middle socio-economic classes. Three groups were studied: Illiterate;1-4 schooling years; 5-8 schooling years. The new version (MMSEmo) consisted of modifications in copy and calculation items of the adapted MMSE (MMSEad) to Portuguese language. The maximum possible score was the same in the two versions: total, 30; copy, 1 and calculation, 5. RESULTS In the total test score ANOVA detected main effects for education and test, as well as an interaction between these factors: higher schooling individuals performed better than lower schooling ones in both test versions; scores in MMSE-mo were higher than in MMSE-ad in every schooling group. CONCLUSION Higher schooling levels improve the performance in both test versions, the copy and calculation items contributing to this improvement. This might depend on cultural factors. The use of MMSE-mo in illiterate and low school individuals could prevent false positive and false negative cognitive evaluations.
Digital self-calibration method for MEMS sensors

This paper presents a digital self-calibration method for microelectromechanical systems (MEMS) using a relay-feedback loop and a set of discrete-time filters. This method is based on the measurement of limit-cycles at the comparator's output, which result from a synchronization phenomenon between the natural frequency of the MEMS and the clock frequency of the discrete-time components. We show how quantized information concerning the MEMS parameters may be extracted from the shape of the limit-cycle, which depends on the characteristics of the MEMS (pulsation, damping, etc.). This digital technique is amplitude-independent, relatively insensitive to noise, and not costly to implement. Details concerning its implementation are discussed, and some simulation and experimental results are given.
The relationship between remoteness and trauma deaths in Western Australia.

BACKGROUND Mortality from trauma in rural areas is increased compared with the urban environment. We aimed to describe the relationship between trauma deaths and various categories of remoteness in rural areas, in Western Australia (WA). METHODS We used Death Registry data from July 1, 1997 to June 30, 2006. Deaths were allocated to one of the five Remoteness Areas classified by the Accessibility/ Remoteness Index of Australia: Major Cities, Inner Regional, Outer Regional, Remote, and Very Remote. Population data were obtained from the Australian Bureau of Statistics 2001 census. RESULTS There were 4,937 deaths (3,543, 71.8% men; mean age 43.4 years +/- 24.3 years). The least number of deaths occurred in Remote WA, and the age at which death occurred decreased as remoteness increased. Falls occur predominantly in the elderly in the major city. Transport injuries are the leading cause of death (43.3%) outside the major city, where self harm is the leading cause of death (31.2%). The relative risk for death in very remote WA compared with the major city is 4.28 (95% CI 3.93-4.68). The standardized age-specific death rates ranged from 24.09 per 100,000 person-years in the major city, to 103.30 per 100,000 person-years in very remote WA. CONCLUSIONS We have quantified the direct relationship between remoteness and trauma deaths. In particular, the death rate in very remote areas is over four times the rate in major cities. Such data should be useful for the planning of trauma systems in these areas.
Effects of Halothane on Sarcoplasmic Reticulum Calcium Release Channels in Porcine Airway Smooth Muscle Cells

BackgroundVolatile anesthetics relax airway smooth muscle (ASM) by altering intracellular Ca2+ concentration ([Ca2+]i). The authors hypothesized that relaxation is produced by decreasing sarcoplasmic reticulum Ca2+ content via increased Ca2+ “leak” through both inositol trisphosphate (IP3) and ryanodine receptor channels. MethodsEnzymatically dissociated porcine ASM cells were exposed to acetylcholine in the presence or absence of 2 minimum alveolar concentration (MAC) halothane, and IP3 levels were measured using radioimmunoreceptor assay. Other cells were loaded with the Ca2+ indicator fluo-3 and imaged using real-time confocal microscopy. ResultsHalothane increased IP3 concentrations in the presence and absence of acetylcholine. Inhibition of phospholipase C blunted the IP3 response to halothane. Exposure to 2 MAC halothane induced a transient [Ca2+]i response, suggesting depletion of sarcoplasmic reticulum Ca2+. Exposure to 20 &mgr;m Xestospongin D, a cell-permeant IP3 receptor antagonist, resulted in a 45 ± 13% decrease in the [Ca2+]i response to halothane compared with halothane exposure alone. In permeabilized cells, Xestospongin D or 0.5 mg/ml heparin decreased the [Ca2+]i response to halothane by 65 ± 13% and 68 ± 22%, respectively, compared with halothane alone. In both intact and permeabilized cells, 20 &mgr;m ryanodine blunted the [Ca2+]i response to halothane by 32 ± 13% and 39 ± 21%, respectively, compared with halothane alone. Simultaneous exposure to Xestospongin D and ryanodine completely inhibited the [Ca2+]i response to halothane. ConclusionsThe authors conclude that halothane reduces sarcoplasmic reticulum Ca2+ content in ASM cells via increased Ca2+ leak through both IP3 receptor and ryanodine receptor channels. Effects on IP3 receptor channels are both direct and indirect via elevation of IP3 levels.
Long-term effectiveness of the Diabetes Conversation Map Program

Abstract Health education is compulsory for patients with chronic and life-threatening disease, especially for those with diabetes mellitus (DM). This study aimed to examine the long-term effectiveness of the Diabetes Conversation Map Program (DCMP) among DM patients in Taiwan. A quasi-experimental research design using convenience sampling and nonrandom group assignment was applied to recruit 95 type 2 diabetic subjects from a hospital in Taiwan. In addition to routine care, the experiment group (n = 49) received 7 sessions of DCMP that delivered over 2 months, while the control group (n = 46) received only routine care during the same period. We conducted structured questionnaire survey and reviewed medical record at 3 time points (before DCMP, 3 days after DCMP, and 3 months after DCMP completion) to collect the effectiveness data. The effectiveness was determined using the generalized estimating equation model. We found that improvements in the body mass index, blood glucose, glycated hemoglobin, self-monitoring of blood glucose, and diabetic health literacy in the DCMP group compared with controls (all P values <.05), with no significant changes in depressive symptoms. The positive effects were further maintained for 3 months after DCMP. The findings may serve as a reference for helping healthcare professionals provide appropriate interventions to improve adaptation processes and clinical outcomes for DM patients.
The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity*

Bone formation requires the coordinated activity of numerous proteins including the transcription factor core-binding factor α1 (Cbfa1). Deregulation of Cbfa1 results in metabolic bone diseases including osteoporosis and osteopetrosis. The retinoblastoma protein (pRb) that is required for osteogenesis binds Cbfa1. We reported earlier that the p200 family protein p204, which is known to be involved in the differentiation of skeletal muscle myotubes, cardiac myocytes, and macrophages, also serves as a cofactor of Cbfa1 and promotes osteogenesis. In this study we established that suppression of p204 expression by an adenovirus construct encoding p204 antisense RNA inhibited osteoblast-specific gene activation by Cbfa1 in an osteogenesis assay involving the pluripotent C2C12 mesenchymal cell line. Using protein-protein interaction assays we established that Cbfa1, pRb, and p204 form a ternary complex in which pRb serves as a linker connecting p204 and Cbfa1. Chromatin immunoprecipitation assays revealed the binding of such a p204-pRb-Cbfa1 transcription factor complex to the promoter of the osteocalcin gene. The pRb requirement of the stimulation of Cbfa1 activity by p204 was established in experiments involving p204 mutants lacking one or two pRb binding (LXCXE) motifs. Such mutants failed to enhance the Cbfa1-dependent transactivation of gene expression as well as osteogenesis. Furthermore, as revealed in reporter gene and in vitro osteogenesis assays p204 synergized with pRb in the stimulation of Cbfa1-dependent gene activation and osteoblast differentiation.
The impact of parental absence on early childhood development in the context of Thailand

This analysis investigates the impact of parental absence on early childhood development in Thailand, using the Denver II screening tool, based on a study conducted in 2013–2014. Children aged 36 months and younger were included (n = 923). Results reveal that the crucial factor for delayed development in early childhood is the mother’s presence in the household. Children who were cared for by others were not at higher risk of delayed development as long as their mother was present, while the father’s absence did not make a difference. This study raises concern for the large number of children living separately from their mothers, and also raises questions about the long-term effects of parental migration for this generation of Thai children.
Applying Positive End-Expiratory Pressure During Mechanical Ventilation Causes Pulmonary Redox Imbalance and Inflammation in Rats

Background: Mechanical ventilation (MV) may induce or aggravate lung injury through the production of cytokines, inflammatory infiltration of neutrophils, and changes in the permeability of the alveolar-capillary barrier. The use of positive end-expiratory pressure (PEEP) helps improve gas exchanges avoiding alveolar collapse at the end of expiration. The present study aimed to analyze inflammatory response and redox imbalance in lungs of rats submitted to MV with and without PEEP. Methods: Eighteen Wistar rats were divided into three groups: control (CG), PEEP group (PG), and zero PEEP (ZEEP) group (ZG). PG and ZG were submitted to MV for 60 min with or without PEEP, respectively. Subsequently, the animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were collected for analyses. Results: The number of neutrophils was higher in PG compared with CG. Leucocyte and neutrophil influx in bronchoalveolar lavage fluid was higher in PG compared with CG. PG showed an increase in alveolar area compared with the other groups. There were increases in the levels of chemokines, CCL3 and CCL5, in PG compared with CG. There were increases in oxidation of lipids and proteins in PG compared with other groups. There were increases in the activity of superoxide dismutase and catalase in PG compared with CG and ZG. However, there was a decrease in the ratio of glutathione to glutathione disulfide in PG compared with other groups. Conclusions: MV with PEEP caused redox imbalance and inflammation in lungs of healthy rats.
Real-time PCR method for the detection of the gene encoding surface lipoprotein LipL32 of pathogenic Leptospira: use in the laboratory diagnosis of the acute form of leptospirosis

Abstract Background: The aims of this work were to replace the obsolete PCR method for the laboratory diagnosis of the acute form of leptospirosis using the G1, G2 and B64 I, B64 II primers, and to improve the PCR detection time. Methods: We introduced a real-time PCR method for the detection of the gene encoding the surface lipoprotein LipL32 of pathogenic Leptospira into our laboratory diagnosis of the acute form of leptospirosis. The positive and negative analytical specificities of the real-time PCR method were both equal to 100%; the detection limit was determined to be 1–5 genome copies/1 ml of liquid biological material. The method was further validated on 230 laboratory strains of leptospires. Results: All laboratory strains of pathogenic Leptospira were evaluated as LipL32-positive and all non-pathogenic strains as LipL32-negative. In addition, 455 biological materials (253 plasma, 121 urine, 72 cerebrospinal fluid (CSF), 7 bronchoalveolar lavage, and 2 sputum) from 295 patients with suspected leptospirosis were examined. From this set of patients, 9 were evaluated to be LipL32-positive, from 15 positive biological materials (10 urine, 4 blood plasma, and 1 CSF). Conclusions: This real-time PCR method for the detection of the gene encoding the surface lipoprotein LipL32 is a reliable, sensitive, and rapid method for the detection of the acute form of leptospirosis.
The Combined Effect of Age and Premedication on the Propofol Requirements for Induction by Target-Controlled Infusion

In this prospective study, we evaluated the combined influence of age and premedication on propofol requirements for the induction of anesthesia and their hemodynamic effects using a target-controlled infusion. We studied 180 patients separated into three age groups: 20–39 yr, 40–59 yr, and more than 59 yr. In each age group, patients were randomly allocated to receive either no premedication (n = 20), fentanyl (2 &mgr;g/kg) (n = 20), or midazolam (0.03 mg/kg) plus fentanyl (2 &mgr;g/kg) (n = 20). The concentration of propofol targeted for the induction was 5 &mgr;g/mL, to be reached in 2 min. The dose, time, and predicted plasma concentration of propofol at hypnosis were measured. Baseline and postinduction heart rate and arterial blood pressure were registered. Computer simulation was used to calculate the effect site propofol concentration at hypnosis. The concentration of propofol, effect site propofol concentration, time, and induction dose and their hemodynamic effect were significantly different among groups with respect to age and premedication. The combined effect of the two factors was additive, but without significant interaction. The propofol requirements were significantly less in the midazolam-fentanyl groups, regardless of age, and among the premedicated patients older than 60 yr compared with the other age groups. We conclude that the combined effect of age and premedication on the requirements of propofol for the induction of anesthesia should be considered when the concentration is targeted with a target-controlled infusion system. Implications Induction of anesthesia by using a target-controlled infusion system is influenced by both age and premedication. We define the effect site propofol concentration required for hypnosis with an alternative system to that of plasma-effect site equilibration. These findings may have an impact on the induction with pumps targeting an effect site concentration.
Determinants of female entrepreneurship in Iran: An institutional approach

The purpose of this paper is to analyse the factors that influence female entrepreneurship (opportunity and necessity entrepreneurship) in Iran, using institutional economics as the theoretical framework. The empirical research uses the Logit Model and the Multinomial Logit Model to analyse a dataset for Iran based on the Global Entrepreneurship Monitor (GEM) and covering the period 2011–2015. The study concludes that informal factors (fear of failing, entrepreneurial skills, and female networks) are more relevant to female entrepreneurship than formal factors (education and start-up capital). The research recommends that policymakers consider the institutional factors that affect female entrepreneurship in Iran and design support policies to foster female entrepreneurial activity.
Doping the armchair single-walled carbon nanotubes by silicon substitutions: A density functional theory study

In this paper the nanotubes obtained by silicon atoms substitutionally doping the armchair single-walled carbon nanotubes were investigated by quantum chemistry calculations under the framework of density functional theory. The geometrical structures, relative stabilities and electronic properties of the fifteen Si-doped tubes were studied in details and compared with those of the pristine (5, 5) tubes. It is found that the Si atoms tend to “pop out” from the original positions when the silicon atoms are introduced into the nanotubes. The Si-doped nanotubes exhibit lower thermodynamic stability than those of the undoped tubes from viewpoint of cohesive energy, and this is similar to the case of the silicon doped zigzag nanotubes. The energy levels of the frontier orbitals vary very little when the silicon atom is introduced into the nanotubes. However, most hybrid nanotubes present smaller energy gaps than those of the pristine ones.
Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Background Subclinical myocardial injury, as measured by high‐sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus. Methods and Results We randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT‐proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1–Q3) plasma concentration was 35.4 (15.7–86.3) ng/L for NT‐proBNP and 6.7 (4.6–10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT‐proBNP concentration was 20.7% (7.9–35.0) in the insulin arm compared with 0.13% (−10.8 to 12.5) in the no‐insulin arm (P=0.03 for comparison). These changes were not related to changes in fasting or postprandial glucose, glycated hemoglobin, weight, blood pressure, or inflammation. In the metformin arm, the adjusted change in NT‐proBNP was 7.8% (−3.7 to 20.7) compared with 13.0% (0.72–26.8) in the no‐metformin arm (P=0.58). No significant changes in hsTnT concentrations were observed for any of the treatment arms. Conclusions Insulin glargine was associated with a significant 20.7% increase in NT‐proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control. Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT00366301.