Miracle-dz/UniFAR-FTUs huggingface dataset:
Pediatric Mastocytosis: Routine Anesthetic Management for a Complex Disease

BACKGROUND: Pediatric mastocytosis consists of a spectrum of clinical variants characterized by increased numbers of resident mast cells in various organ systems. Mast cells are instrumental in mediating anaphylaxis and patients with mastocytosis are at risk to develop provoked and unprovoked episodes of anaphylaxis. METHODS: We examined perianesthetic records of patients with pediatric mastocytosis who were anesthetized for diagnostic and surgical procedures from 1993 to 2006. In addition, we conducted a literature review of the anesthetic experience in pediatric mastocytosis. RESULTS: Twenty-two patients with pediatric mastocytosis, with a median age of 3.2 yr (range, 6 mo–20 yr) at the time of the procedure, were anesthetized for 29 diagnostic and surgical procedures. All variants of the disease are represented in this series. Most patients had a history of flushing, pruritus, gastro-esophageal reflux diseases, and abdominal pain; one patient had a history of spontaneous anaphylaxis. Routine anesthetic techniques were used and, despite the complexity of the disease, the perioperative courses were uncomplicated and without serious adverse events. CONCLUSIONS: We reviewed the main features of pediatric mastocytosis, its anesthetic and perioperative implications, and describe a practical approach to the anesthetic management of pediatric patients with the disease. Although many drugs used routinely in anesthesia reportedly caused mast cell degranulation, deviations from routine anesthesia techniques are not necessarily warranted. However, an understanding of the anesthetic implications of the disease and meticulous preparation to treat possible adverse events are advised.
Relationship between repetitive behaviour and fear across normative development, autism spectrum disorder, and down syndrome

The present study had two aims: first to compare levels of restricted and repetitive behaviours (RRB) across two groups of typically developing (TD) children, and two disorders: Autism Spectrum Disorder (ASD) and Down syndrome (DS), and second to explore the relationship between fear and repetitive behaviours in these four groups. Parents of 41 offspring with ASD (Mage = 123.39 months, SDage = 27.67), 38 offspring with DS (Mage = 125.37 months, SDage = 45.71), 45 typically developing children matched to the mental age (MA) of the DS group (TD MA; Mage = 51.13 months, SDage = 22.1), and 42 chronological age (TD CA; Mage = 117.93 months, SDage = 22.91) matched TD children, completed measures of RRB and fear. ANOVAs revealed differences across the four groups on the RRB subscale scores: “Just Right” F(3,162) = 16.62, P < 0.001; Rigid Routines F(3,162) = 52.76, P < 0.001; Sensory behaviours F(3,162) = 23.26, P < 0.001. Post‐hoc comparisons revealed that children with ASD had the highest RRB levels followed by DS, TD MA, and TD CA children. In children with ASD, higher levels of fear were related to higher RRB levels. Similar, albeit less strong, patterns of associations was found among DS and TD MA children but not in older TD CA children. This study provided evidence of a fear‐RRB association in children with ASD, DS, and two groups of TD children. Autism Res 2017, 10: 502–507. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
If Only my Leader Would just Do Something! Passive Leadership Undermines Employee Well‐being Through Role Stressors and Psychological Resource Depletion

The goal of this study was to develop and test a sequential mediational model explaining the negative relationship of passive leadership to employee well-being. Based on role stress theory, we posit that passive leadership will predict higher levels of role ambiguity, role conflict and role overload. Invoking Conservation of Resources theory, we further hypothesize that these role stressors will indirectly and negatively influence two aspects of employee well-being, namely overall mental health and overall work attitude, through psychological work fatigue. Using a probability sample of 2467 US workers, structural equation modelling supported the model by showing that role stressors and psychological work fatigue partially mediated the negative relationship between passive leadership and both aspects of employee well-being. The hypothesized, sequential indirect relationships explained 47.9% of the overall relationship between passive leadership and mental health and 26.6% of the overall relationship between passive leadership and overall work attitude. Copyright © 2016 John Wiley & Sons, Ltd.
Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium

Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100‐fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4‐pyridylmethanol by whole cells and cell‐free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro‐generated mutants revealed that the major resistance mechanism for both species is loss of the catalase‐peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate‐deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10‐fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria.
Subsidiary Initiative Taking in Multinational Corporations: The Relationship between Power and Issue Selling

This paper investigates the political maneuvering that accompanies subsidiary initiative taking in multinational corporations. On the basis of an explorative empirical investigation of subsidiary initiative taking in the French subsidiaries of six German MNCs, the paper explores the activities that subsidiaries undertake to sell their initiatives, and the relationships among issue selling, subsidiary power and headquarters’ hierarchical power. The findings suggest that the use of issue-selling tactics is common when subsidiaries engage in initiative taking. In addition, the paper demonstrates that a low degree of issue selling is needed to obtain approval of an initiative in less asymmetrical headquarters–subsidiary power relationships (i.e. relationships in which subsidiaries are relatively powerful). In cases where power relationships are highly asymmetrical, issue selling is a necessity, but it is hardly a sufficient condition for obtaining headquarters’ approval. This renders issue selling to a second-rank power in subsidiary initiative taking, as it only works in conjunction with subsidiary power.
Prenatal toxoplasmosis antibody and childhood autism

There is evidence that some maternal infections during the prenatal period are associated with neurodevelopmental disorders, such as childhood autism. However, the association between autism and Toxoplasma gondii (T. gondii), an intracellular parasite, remains unclear. The authors examined whether serologically confirmed maternal antibodies to T. gondii are associated with odds of childhood autism in offspring. The study is based on a nested case‐control design of a large national birth cohort (N = 1.2 million) and the national psychiatric registries in Finland. There were 874 cases of childhood autism and controls matched 1:1 on date of birth, sex, birthplace and residence in Finland. Maternal sera were prospectively assayed from a national biobank for T. gondii IgM and IgG antibodies; IgG avidity analyses were also performed. High maternal T. gondii IgM antibody was associated with a significantly decreased odds of childhood autism. Low maternal T. gondii IgG antibody was associated with increased offspring odds of autism. In women with high T. gondii IgM antibodies, the IgG avidity was high for both cases and controls, with the exception of three controls. The findings suggest that the relationship between maternal T. gondii antibodies and odds of childhood autism may be related to the immune response to this pathogen or the overall activation of the immune system. Autism Res 2017, 10: 769–777. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Growth hormone prevents human monocytic cells from Fas‐mediated apoptosis by up‐regulating Bcl‐2 expression

Apoptosis and particularly Fas‐mediated apoptosis has been proposed to play a key role in controlling monocyte homeostasis. We and others have documented the regulatory function of human growth hormone (hGH) on monocytic cells, which prompted us to investigate the role of hGH on their response to Fas antigen cross‐linking. Using human promonocytic U937 cells constitutively producing hGH upon gene transfer and human primary monocytes cultured in the presence of recombinant hGH, we demonstrated that hGH diminished Fas‐mediated cell death by enhancing the expression of the antiapoptotic oncoprotein Bcl‐2 as well as the level of bcl‐2α mRNA. In parallel, we established that overexpression of Bcl‐2 through gene transfer into normal U937 cells also diminished Fas‐induced apoptosis. Further, as a result of Bcl‐2 overexpression, we found that hGH greatly depressed Fas‐induced activation of the cysteine protease caspase‐3 (CPP32), which in turn affected the cleavage of poly(ADP‐ribose) polymerase. Altogether, these data provide evidence that hGH mediates its protective effect through a Bcl‐2‐dependent pathway, clearly a crucial step in enhanced survival of monocytic cells exposed to Fas‐induced death.
Clinical sensitivity and specificity of meconium fatty acid ethyl ester, ethyl glucuronide, and ethyl sulfate for detecting maternal drinking during pregnancy.

BACKGROUND We investigated agreement between self-reported prenatal alcohol exposure (PAE) and objective meconium alcohol markers to determine the optimal meconium marker and threshold for identifying PAE. METHODS Meconium fatty acid ethyl esters (FAEE), ethyl glucuronide (EtG), and ethyl sulfate (EtS) were quantified by LC-MS/MS in 0.1 g meconium from infants of Safe Passage Study participants. Detailed PAE information was collected from women with a validated timeline follow-back interview. Because meconium formation begins during weeks 12-20, maternal self-reported drinking at or beyond 19 weeks was our exposure variable. RESULTS Of 107 women, 33 reported no alcohol consumption in pregnancy, 16 stopped drinking by week 19, and 58 drank beyond 19 weeks (including 45 third-trimester drinkers). There was moderate to substantial agreement between self-reported PAE at ≥19 weeks and meconium EtG ≥30 ng/g (κ = 0.57, 95% CI 0.41-0.73). This biomarker and associated cutoff was superior to a 7 FAEE sum ≥2 nmol/g and all other individual and combination marker cutoffs. With meconium EtG ≥30 ng/g as the gold standard condition and maternal self-report at ≥19 weeks' gestation as the test condition, 82% clinical sensitivity (95% CI 71.6-92.0) and 75% specificity (95% CI 63.2-86.8) were observed. A significant dose-concentration relationship between self-reported drinks per drinking day and meconium EtG ≥30 ng/g also was observed (all P < 0.01). CONCLUSIONS Maternal alcohol consumption at ≥19 weeks was better represented by meconium EtG ≥30 ng/g than currently used FAEE cutoffs.
Transcranial Sonography and DaTSCAN in Early Stage Parkinson's Disease and Essential Tremor

Background: The diagnosis of Parkinson's disease (PD) can sometimes be a challenge in the early stages of the disease. Both transcranial sonography (TCS) and DaTSCAN are recommended as auxiliary examinations for the differential diagnosis of PD; however, only few data exist regarding their diagnostic accuracy in the early stage of PD and essential tremor (ET). Methods: We evaluated patients with clinically suspected diagnosis of PD at early stages (Hoehn and Yahr ≤2) or ET. All patients underwent DaTSCAN and TCS with a maximum interval of 6 months. Final diagnosis was established after 1-year follow-up. Results: From the 63 patients recruited, 3 were excluded due to transcranial insonability and 2 for uncertain clinical diagnosis. The final clinical diagnosis was ET in 44.8% and PD in 55.2%. Compared to clinical diagnosis of PD, TCS had a sensitivity of 87.5% and specificity of 96.2%; DaTSCAN sensitivity was 84.4% and specificity was 96.2%. Both diagnostic tests demonstrated a substantial level of agreement (Cohen's kappa coefficient: 0.83, 95% CI 0.68-0.97, p < 0.001). Conclusion: TCS and DaTSCAN have similar diagnostic accuracy for the diagnosis of early stage PD versus ET.
Association between serum 25‐hydroxyvitamin D and serum sex steroid hormones among men in NHANES

Recent literature suggests that high circulating vitamin D may increase prostate cancer risk. Although the mechanism through which vitamin D may increase risk is unknown, vitamin D concentration could influence circulating sex steroid hormones that may be associated with prostate cancer; an alternate explanation is that it could be associated with prostate‐specific antigen (PSA) concentration causing detection bias.
Prevalence and awareness of CKD among African Americans: the Jackson Heart Study.

BACKGROUND Chronic kidney disease (CKD) leads to end-stage renal disease and is a growing epidemic throughout the world. In the United States, African Americans have an incidence of end-stage renal disease 4 times that of whites. STUDY DESIGN Cross-sectional to examine the prevalence and awareness of CKD in African Americans. SETTING & PARTICIPANTS Observational cohort in the Jackson Heart Study (JHS). PREDICTOR CKD was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2), the presence of albuminuria, or dialysis therapy. OUTCOMES & MEASUREMENTS Data from the JHS were analyzed. Medical history, including disease awareness and drug therapy, anthropometric measurements, and serum and urine samples, were obtained from JHS participants at the baseline visit. Associations between CKD prevalence and awareness and selected demographic, socioeconomic, health care access, and disease status parameters were assessed by using logistic regression models. RESULTS The prevalence of CKD in the JHS was 20%; CKD awareness was only 15.8%. Older participants had a greater prevalence, but also were more aware of CKD. Hypertension, diabetes, cardiovascular disease, hypercholesterolemia, hypertriglyceridemia, increasing age and waist circumference, and being single or less physically active were associated with CKD. Only advancing CKD stage was associated with awareness. LIMITATIONS Cross-sectional assessment, single urine measurement. CONCLUSIONS The JHS has a high prevalence and low awareness of CKD, especially in those with less severe disease status. This emphasizes the need for earlier diagnosis and increased education of health care providers and the general population.
DArT whole genome profiling provides insights on the evolution and taxonomy of edible Banana (Musa spp.)

Background and Aims Dessert and cooking bananas are vegetatively propagated crops of great importance for both the subsistence and the livelihood of people in developing countries. A wide diversity of diploid and triploid cultivars including AA, AB, AS, AT, AAA, AAB, ABB, AAS and AAT genomic constitutions exists. Within each of this genome groups, cultivars are classified into subgroups that are reported to correspond to varieties clonally derived from each other after a single sexual event. The number of those founding events at the basis of the diversity of bananas is a matter of debate. Methods We analysed a large panel of 575 accessions, 94 wild relatives and 481 cultivated accessions belonging to the section Musa with a set of 498 DArT markers previously developed. Key Results DArT appeared successful and accurate to describe Musa diversity and help in the resolution of cultivated banana genome constitution and taxonomy, and highlighted discrepancies in the acknowledged classification of some accessions. This study also argues for at least two centres of domestication corresponding to South-East Asia and New Guinea, respectively. Banana domestication in New Guinea probably followed different schemes that those previously reported where hybridization underpins the emergence of edible banana. In addition, our results suggest that not all wild ancestors of bananas are known, especially in M. acuminata subspecies. We also estimate the extent of the two consecutive bottlenecks in edible bananas by evaluating the number of sexual founding events underlying our sets of edible diploids and triploids, respectively. Conclusions The attribution of clone identity to each sample of the sets allowed the detection of subgroups represented by several sets of clones. Although morphological characterization of some of the accessions is needed to correct potentially erroneous classifications, some of the subgroups seem polyclonal.
Reorganisation of healthcare services for children and families: Improving collaboration, service quality, and worker well-being

ABSTRACT This study is an evaluation of a reorganisation of different services for children and their families in a Norwegian municipality. The main aim of the reorganisation was to improve interprofessional collaboration through integrating different social services for children and their parents. The evaluation was guided by the Job Demands-Resources Model with a focus on social and healthcare workers’ experiences of their work, including job demands and resources, service quality, and well-being at work. The survey of the employees was conducted at three measurement points: before (T1) and after (T2, T3) the reorganisation took place, and included between 87 and 122 employees. A secondary aim was to examine the impact of different job resources and job demands on well-being (burnout, engagement, job satisfaction), and service quality. A one-way ANOVA indicated a positive development on many scales, such as collaboration, work conflict, leadership, and perceived service quality, especially from T1 to T2. No changes were detected in burnout, engagement, or job satisfaction over time. Moderated regression analyses (at T3) indicated that job demands were particularly associated with burnout, and job resources with engagement and job satisfaction. Perceived service quality was predicted by both job demands and resources, in addition to the interaction between workload and collaboration. The reorganisation seems to have contributed to a positive development in how collaboration, work conflict, leadership, and service quality were evaluated, but that other changes are needed to increase worker well-being. The value of the study rests on the findings that support co-locating and merging services for children and their families, and that collaboration is an important resource for healthcare professionals.
Down-Regulation of Nucleosomal Binding Protein HMGN1 Expression during Embryogenesis Modulates Sox9 Expression in Chondrocytes

ABSTRACT We find that during embryogenesis the expression of HMGN1, a nuclear protein that binds to nucleosomes and reduces the compaction of the chromatin fiber, is progressively down-regulated throughout the entire embryo, except in committed but continuously renewing cell types, such as the basal layer of the epithelium. In the developing limb bud, the expression of HMGN1 is complementary to Sox9, a master regulator of the chondrocyte lineage. In limb bud micromass cultures, which faithfully mimic in vivo chondrogenic differentiation, loss of HMGN1 accelerates differentiation. Expression of wild-type HMGN1, but not of a mutant HMGN1 that does not bind to chromatin, in Hmgn1 −/− micromass cultures inhibits Sox9 expression and retards differentiation. Chromatin immunoprecipitation analysis reveals that HMGN1 binds to Sox9 chromatin in cells that are poised to express Sox9. Loss of HMGN1 elevates the amount of HMGN2 bound to Sox9, suggesting functional redundancy among these proteins. These findings suggest a role for HMGN1 in chromatin remodeling during embryogenesis and in the activation of Sox9 during chondrogenesis.
Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin

Engineered Salmonella secreting heterologous bacterial flagellin suppress tumor growth by activating intratumoral macrophages. Two bacteria can be better than one In some cases, injecting tumors with specific bacteria can help eradicate the tumors by stimulating inflammation and triggering an antitumor immune response. A classic example of this is injection of bladder cancer with bacillus Calmette-Guérin, but more recent approaches have used bacteria such as Clostridium and Salmonella species. Building on the idea of antitumor bacterial therapy, Zheng et al. engineered a weakened strain of Salmonella typhimurium to produce the flagellin B protein from another bacterium, Vibrio vulnificus. The engineered bacteria induced an effective antitumor immune response, successfully treating tumors in several different mouse models with no evidence of toxicity. We report a method of cancer immunotherapy using an attenuated Salmonella typhimurium strain engineered to secrete Vibrio vulnificus flagellin B (FlaB) in tumor tissues. Engineered FlaB-secreting bacteria effectively suppressed tumor growth and metastasis in mouse models and prolonged survival. By using Toll-like receptor 5 (TLR5)–negative colon cancer cell lines, we provided evidence that the FlaB-mediated tumor suppression upon bacterial colonization is associated with TLR5-mediated host reactions in the tumor microenvironment. These therapeutic effects were completely abrogated in TLR4 and MyD88 knockout mice, and partly in TLR5 knockout mice, indicating that TLR4 signaling is a requisite for tumor suppression mediated by FlaB-secreting bacteria, whereas TLR5 signaling augmented tumor-suppressive host reactions. Tumor microenvironment colonization by engineered Salmonella appeared to induce the infiltration of abundant immune cells such as monocytes/macrophages and neutrophils via TLR4 signaling. Subsequent secretion of FlaB from colonizing Salmonella resulted in phenotypic and functional activation of intratumoral macrophages with M1 phenotypes and a reciprocal reduction in M2-like suppressive activities. Together, these findings provide evidence that nonvirulent tumor-targeting bacteria releasing multiple TLR ligands can be used as cancer immunotherapeutics.