Miracle-dz/UniFAR-FTUs huggingface dataset:
Anidulafungin Pharmacokinetics and Microbial Response in Neutropenic Mice with Disseminated Candidiasis

ABSTRACT Candidemia is often fatal, especially in patients with persistent neutropenia. New therapies are needed. We performed 24-h pharmacodynamic studies to compare the efficacies of anidulafungin, fluconazole, and amphotericin B in neutropenic mice with disseminated candidiasis caused by one of three strains of Candida glabrata. Anidulafungin produced a maximal fungal kill (Emax) of 1.4 to 1.9 log10 CFU/g in kidneys and was not influenced by resistance to either fluconazole or amphotericin B. Fluconazole produced an Emax of 1.3 log10 CFU/g in mice infected with fluconazole-susceptible C. glabrata, but the Emax was 0 for mice infected with a C. glabrata strain that had a fluconazole MIC of ≥32 mg/liter. Amphotericin B achieved an Emax of 4.2 log10 CFU/g in mice infected with amphotericin B-susceptible C. glabrata, but the Emax was 0 for mice infected with a C. glabrata strain with an amphotericin B MIC of 2 mg/liter. In all instances, anidulafungin's maximal microbial kill was superior to that of fluconazole. Next, we performed a 96-h anidulafungin pharmacokinetic-pharmacodynamic study. Anidulafungin exhibited delayed peak concentrations in kidneys compared to those in serum, after which the concentrations declined, with a serum terminal half-life of 21.6 (±4.6) h. This was accompanied by a persistent 96-h decrease in the kidney fungal burden after treatment with a single anidulafungin dose of ≥8 mg/kg of body weight. This pharmacokinetic-pharmacodynamic picture of anidulafungin persistence in tissues and the resultant persistent fungal decline should be exploited to improve the efficacy of anidulafungin therapy for candidemia.
The Impact of Government Regulation on Recruitment Process, Rights, Wages and Working Conditions of Labor Migrants in the Israeli Construction Sector

To determine the impact of evolving forms of governance on migrant workers&#8217; rights and employment conditions in Israel we first probe the extensive private recruitment industry that developed in Israel before the implementation of bilateral agreements, and examine migrant workers&#8217; employment conditions and wages. Next we show the importance of bilateral agreements for the annulment of illicit practices in labor recruitment, as well as the practical consequences for migrants under the new arrangement. Specifically we scrutinize the impact of implementation of bilateral agreements in the construction sector on recruitment practices and fees, wage levels, and work conditions. Implementation of bilateral agreement were accompanied by dramatic decrease in the sums paid by migrant workers to reach the host country &#8211; but did not significantly improve workers&#8217; rights, and their wages even declined. The mechanisms whereby a pool of precarious workers has emerged in the local labor market in Israel are highlighted.
Warm antibody autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test-negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed.
GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease.

Previous studies have shown that patients with deletion of distal human chromosome arm 8p may have congenital heart disease and other physical anomalies. The gene encoding GATA-4, a zinc finger transcription factor implicated in cardiac gene expression and development, localizes to chromosome region 8p23.1. To examine whether GATA-4 deficiency is present in patients with monosomy of 8p23.1 with congenital heart disease, we performed fluorescence in situ hybridization (FISH) with a GATA4 probe on cells from a series of patients with interstitial deletion of 8p23.1. Four individuals with del(8)(p23.1) and congenital heart disease were found to be haploinsufficient at the GATA4 locus by FISH. The GATA4 gene was not deleted in a fifth patient with del(8)(p23.1) who lacked cardiac anomalies. FISH analysis on cells from 48 individuals with congenital heart disease and normal karyotypes failed to detect any submicroscopic deletions at the GATA4 locus. We conclude that haploinsufficiency at the GATA4 locus is often seen in patients with del(8)(p23.1) and congenital heart disease. Based on these findings and recent studies showing that haploinsufficiency for other cardiac transcription factor genes (e.g., TBX5, NKX2-5) causes congenital heart disease, we postulate that GATA-4 deficiency may contribute to the phenotype of patients with monosomy of 8p23.1.
Heat-induced membrane damage combined with adriamycin on prostate carcinoma PC-3 cells: correlation of cytotoxicity, permeability and P-glycoprotein or metallothionein expression.

OBJECTIVE To assess heat-induced membrane damage in a prostate cancer cell line when combined with adriamycin treatment. MATERIALS AND METHODS The changes in intracellular adriamycin accumulation, cell proliferation and cell-cycle fractions were examined after human prostate carcinoma PC-3 cells were exposed to heat and/or further treatment with adriamycin. Proliferation and the cell cycle were determined using adherent cell analysis and sorting laser cytometry (ACAS) or flow cytometry. P-glycoprotein (PGP) and metallothionein (MT) expression, which may have a physiological role in the transport of or reduction in cytotoxicity of some anticancer drugs, were also analysed after cells were exposed to heat, using immunohistochemical or flow cytometric methods. RESULTS There was a significant increase in intracellular adriamycin accumulation, related to both influx (P<0.05) and efflux (P<0.01), in cells treated with adriamycin, especially after heating them at 44 degrees C for 1 h. There was a significant decrease in cell proliferation of preheated cells when exposed to adriamycin, especially at 44 degrees C (P<0.05). In the cell-cycle analysis, cells preheated at 44 degrees C showed partial accumulation in the debris or apoptotic fraction at 24 h, and many cells accumulated in these fractions at 48 h. There was significantly less PGP or MT expression in cells preheated at 44 degrees C than in control cells or cells preheated at 41 degrees C (P<0.01). This reduction in PGP or MT level by heating may inhibit drug efflux and thus increase intracellular drug level at elevated temperatures. CONCLUSIONS These results suggest that hyperthermia may damage the drug-exclusion mechanism in these cells and thus increase the effectiveness of drug action.
Assessing the Norms and Standards of School Mentors’ Competences in the 1+1 Model of Initial Primary Teacher Education in Malawi: Implications for Mentor Development

Abstract The aim of this comparative cross-sectional study was to assess the competences of school mentors in the Initial Primary Teacher Education (IPTE) mode from the perspective of student teachers and headteachers. The study set out to find answers to the following research questions: (1) what are the competences of school mentors as perceived by student teachers? (2) What are the competences of school mentors as perceived by headteachers? (3) Is there a significant difference in the mean competence scores for student teachers and headteachers? (4) What are the implications of the findings for school mentor development? Ninety-two primary schools and 670 participants comprising 579 student teachers and 91 headteachers participated in a mixed methods research design in which a census survey was followed by a case study of two schools to observe the practices of mentoring for purposes of triangulation and complementarity. Data was analysed by employing descriptive analysis and calculating independent-sample t-test. The results revealed that at student teacher respondents generally confirmed that school mentors demonstrated competency in most of the mentoring aspects under investigation. Very few respondents indicated that mentors did not demonstrate the investigated competencies. The same results were revealed by headteachers about their school mentors. An independent-sample t-test revealed that there was no statistical significant difference in 28 of the 30 competence scores of assessment by the student teachers and headteachers. Significant difference was found in only two competences.
Convergence and Polarization in Regional Income Levels: The Role of International Technology Diffusion

This study investigates the effects of three international technology diffusion (ITD) channels on regional economic convergence (REC): inward foreign direct investment (IFDI), outward foreign direct investment (OFDI) and imports. Based on Chinese provincial-level data, econometric results suggest a converging trend of per capita income levels in China during 2004-2009. This study also confirms that IFDI has a negative effect on REC. This is due to the concentration of IFDI in comparatively developed regions (CDRs) and weak absorptive capacity of less developed regions. OFDI in developed countries (DCs) has a positive effect on REC, however, OFDI in transitional and emerging economies (TEEs) will lead to a wider income gap. In addition, imports fail to promote REC because of a high volume of imports of goods instead of services, as well as a concentration of capital goods. This study further confirms the convergence pattern of East, Middle and West China.
NBER WORKING PAPER SERIES WELFARE REFORM AND HEALTH INSURANCE COVERAGE OF LOW-INCOME FAMILIES

We study whether welfare reform adversely affected the health insurance coverage of low-educated single mothers and their children. Specifically, we investigate whether changes in the welfare caseload during the 1990s were associated with changes in Medicaid participation, private insurance coverage, and the number of uninsured among single mothers and their children. Estimates suggest that between 1996 and 1999, the 42 percent decrease in the welfare caseload was associated with the following changes in insurance coverage among low-educated, single mothers: a seven to nine percent decrease in Medicaid coverage; an increase in employer-sponsored, private insurance coverage of six percent; and a two to nine percent increase in the proportion uninsured. Among children of low-educated, single mothers, effects were somewhat smaller. Since welfare policy was responsible for only part (e.g., one-third) of the decline in the caseload, welfare reform per se had significantly smaller effects on the health insurance status of low-income families. However, we found limited evidence that changes in the caseload due to state and federal welfare policy had fewer adverse consequences on insurance status than changes in the caseload due to other factors. This implies even smaller effects of welfare reform. Robert Kaestner Institute of Government and Public Affairs University of Illinois at Chicago 815 W. Van Buren Street, Suite 525 Chicago, IL 60607 and NBER kaestner@uic.edu Neeraj Kaushal School of Social Work Columbia University 622 West 113 Street New York, NY 10025
Signaling of de‐adhesion in cellular regulation and motility

Adhesion is a process that can be divided into three separate stages: (1) cell attachment, (2) cell spreading, and (3) the formation of focal adhesions and stress fibers. With each stage the adhesive strength of the cell increases. De‐adhesion can be defined as the process involving the transition of the cell from a strongly adherent state, characterized by focal adhesions and stress fibers, to a state of intermediate adherence, represented by a cell that is spread, but that lacks stress fibers terminating at adhesion plaques. We propose that this modification of the structural link between the actin cytoskeleton and the extracellular matrix results in a more malleable cellular state conducive for dynamic processes such as cytokinesis, mitogenesis, and motility. Anti‐adhesive proteins, including thrombospondin, tenascin, and SPARC, rapidly signal de‐adhesion, potentially mediating proliferation and migration during development and wound healing. Intracellular signaling molecules involved in the regulation of de‐adhesion are only beginning to be identified. Interestingly, many of the same signaling proteins recognized to play important roles during the process of adhesion have also been found to act during de‐adhesion. Characterization of the precise mechanisms by which these signals modulate adhesive structures and the cytoskeleton will further our understanding of the regulation of adhesive strength and its function in cellular physiology. Microsc. Res. Tech. 43:420–432, 1998. © 1998 Wiley‐Liss, Inc.
Recidivism after release from a prison nursery program.

OBJECTIVE To analyze 3-year recidivism after release from a prison nursery, a secure unit that allows imprisoned women to care for their infants. DESIGN AND SAMPLE Descriptive study of 139 women who co-resided with their infants between 2001 and 2007 in a New York State prison nursery. MEASURES Administrative criminal justice data were analyzed along with prospective study data on demographic, mental health, and prison nursery policy-related factors. RESULTS Results reflect a sample of young women of color with histories of clinically significant depressive symptoms and substance dependence, who were convicted of nonviolent crimes and had multiple prior arrests. Three years after release 86.3% remained in the community. Only 4% of women returned to prison for new crimes. Survival modeling indicated that women who had previously violated parole had a significantly shorter mean return to prison time than those who were in the nursery for a new crime. CONCLUSION Women released from a prison nursery have a low likelihood of recidivism. Innovative interventions are needed to address incarceration's public health effects. Nurses can partner with criminal justice organizations to develop, implement, and evaluate programs to ensure the health needs of criminal justice involved people and their families are met.
A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder

Objective Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. Method Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. Results Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. Conclusion This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response.
Decreased carotid intima–media thickness in patients with coronary artery ectasia compared with patients with coronary artery disease

BackgroundAlthough atherosclerosis is supposed to be responsible for more than 50% of coronary artery ectasia, the precise pathology of coronary artery ectasia is not clearly understood. A histopathological examination of ectatic segments has revealed mainly destruction of the media layer of the artery. In the present study, we assessed carotid intima–media thickness and common carotid artery diameter in patients with and without coronary artery ectasia. Materials and methodsThirty-five consecutive patients with coronary artery ectasia and coronary artery disease and 35 age and sex-matched patients with coronary artery disease alone were included in the study. The common carotid artery was studied as the longitudinal plane within 10 mm from the bifurcation of the common carotid artery. The intima–media thickness was measured in the far wall at end-diastole from the B-mode screen to a point within the 10-mm segment proximal to the bifurcation by one investigator blinded to clinical data. ResultsNo significant differences with respect to age, body mass index, hypertension, diabetes mellitus, hypercholesterolemia and smoking habits were observed between the two groups studied. Intima–media thickness of the common carotid artery of the patients with coronary artery ectasia was significantly lower than that of the patients with coronary artery disease alone (0.71±0.13 vs. 0.77±0.09 mm, respectively, P=0.04). ConclusionDecreased intima–media thickness of the carotid artery in patients with coronary artery ectasia and coronary artery disease may have pathogenic mechanisms different from coronary artery disease per se.
Exercise Type Affects Cardiac Vagal Autonomic Recovery After a Resistance Training Session

Abstract Mayo, X, Iglesias-Soler, E, Fariñas-Rodríguez, J, Fernández-del-Olmo, M, and Kingsley, JD. Exercise type affects cardiac vagal autonomic recovery after a resistance training session. J Strength Cond Res 30(9): 2565–2573, 2016—Resistance training sessions involving different exercises and set configurations may affect the acute cardiovascular recovery pattern. We explored the interaction between exercise type and set configuration on the postexercise cardiovagal withdrawal measured by heart rate variability and their hypotensive effect. Thirteen healthy participants (10 repetitions maximum [RM] bench press: 56 ± 10 kg; parallel squat: 91 ± 13 kg) performed 6 sessions corresponding to 2 exercises (Bench press vs. Parallel squat), 2 set configurations (Failure session vs. Interrepetition rest session), and a Control session of each exercise. Load (10RM), volume (5 sets), and rest (720 seconds) were equated between exercises and set configurations. Parallel squat produced higher reductions in cardiovagal recovery vs. Bench press (p = 0.001). These differences were dependent on the set configuration, with lower values in Parallel squat vs. Bench press for Interrepetition rest session (1.816 ± 0.711 vs. 2.399 ± 0.739 Ln HF/IRR2 × 104, p = 0.002), but not for Failure session (1.647 ± 0.904 vs. 1.808 ± 0.703 Ln HF/IRR2 × 104, p > 0.05). Set configuration affected the cardiovagal recovery, with lower values in Failure session in comparison with Interrepetition rest (p = 0.027) and Control session (p = 0.022). Postexercise hypotension was not dependent on the exercise type (p > 0.05) but was dependent on the set configuration, with lower values of systolic (p = 0.004) and diastolic (p = 0.011) blood pressure after the Failure session but not after an Interrepetition rest session in comparison with the Control session (p > 0.05). These results suggest that the exercise type and an Interrepetition rest design could blunt the decrease of cardiac vagal activity after exercise while exercising to muscular failure may contribute to the onset of postexercise hypotension.
Increasing NAD Synthesis in Muscle via Nicotinamide Phosphoribosyltransferase Is Not Sufficient to Promote Oxidative Metabolism*

Background: Elevating NAD throughout the body improves oxidative metabolism in skeletal muscle and counteracts effects of high fat feeding. Results: Boosting NAD synthesis specifically in muscle does not recapitulate these effects. Conclusion: NAD content does not limit oxidative metabolism in young, healthy muscles. Significance: Contrary to the presumption of direct, tissue-autonomous effects, the primary sites of action for NAD precursors remain unknown. The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle.