Miracle-dz/UniFAR-FTUs huggingface dataset:
High frequency and diversity of cassette chromosome recombinases (ccr) in methicillin-susceptible Staphylococcus sciuri.

OBJECTIVES Previous studies produced evidence that mecA, the determinant of β-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA), may have originated in the most primitive and widespread animal commensal species-Staphylococcus sciuri. But how the mecA homologue (mecA1/pbpD) was captured from S. sciuri into the staphylococcal cassette chromosome mec (SCCmec) has remained unclear. METHODS To understand the role of S. sciuri in the assembly of SCCmec, we screened 118 methicillin-susceptible S. sciuri isolates for SCCmec central elements-ccr and mec complex (ccrAB, ccrC, mecA, mecI and mecR1)-by dot-blot hybridization. In addition, isolates were typed by PFGE and the chromosomal proximity of SCCmec elements was determined by Southern hybridization. ccr typing was performed by nucleotide sequencing. RESULTS ccrAB were identified in 35% of the isolates (n = 41), represented by 24 PFGE types, but ccrC was not found. None of the isolates carried mecA or its regulators, but all isolates carried mecA1/pbpD. In the majority of isolates, ccr and mecA1 were located near orfX, the SCCmec integration site. Moreover, in 31% (n = 13) of the ccrAB-carrying strains, ccrAB, mecA1 and orfX colocalized in the chromosome. The nucleotide sequence of ccrA/ccrB was highly diverse, including ccr genes closely related (80%-97%) to those found in MRSA. CONCLUSIONS Our results suggest that S. sciuri was a natural recipient and a rich reservoir of ccr for the assembly of SCCmec. The chromosomal location of mecA1, near orfX, the recognition site of ccr, was probably crucial for its mobilization out of S. sciuri species into SCCmec.
New Concept of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma and Its Impact on the Bethesda System for Reporting Thyroid Cytopathology: A Single-Institute Experience

Background: The encapsulated follicular variant (EFV) of papillary thyroid carcinoma (PTC) is the most discussed entity in thyroid pathology. Recently, the question of whether or not EFV-PTC is a malignant entity has been the subject of renewed discussion in the light of recent molecular and clinical studies. The aim of this study was to analyze the malignancy ratios of each category of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) if EFV-PTC is no longer considered as a malignant entity. Materials and Methods: Data on thyroid fine-needle aspirations (n = 1,886) with surgical follow-up between 1999 and 2014 were studied. EFV-PTC cases constituted 27% (94/343) of the malignant cases. Results: Malignancy ratios were determined as nondiagnostic, benign, atypia/follicular lesion of undetermined significance, suspicious for follicular neoplasm/follicular neoplasm, suspicious for malignancy, and malignant categories of the TBSRTC in 13, 7, 45, 30, 72 and 98%, respectively. If EFV-PTC was not regarded as malignant, malignancy ratios would decrease to 6.5, 6, 30, 10, 48, and 87% for each category in the same order. Conclusions: The current study showed that the most significant decrease in relative malignancy ratios was seen in the suspicious for follicular neoplasm/follicular neoplasm category (66% relative decrease), but all categories represented a considerable decrease.
Epistemological access in a science foundation course: a social realist perspective

This dissertation examines how educational practices of a multidisciplinary, integrated science foundation course, Introduction to Science Concepts and Methods (ISCM), at Rhodes University in South Africa, enable and/or constrain epistemological access to a range of mainstream science disciplines. Students in the ISCM course are mainly African, working-class, first-generation higher education learners whose home language is seldom English. This study is motivated firstly by poor success of working-class African students in higher education in South Africa in general and in the sciences in particular, and secondly by the need for closely theorised, empirical work to guide necessary transformational change that will contribute to equity and, thus, to greater social justice. Since I teach in ISCM and coordinate the programme in which it is located, I also have a personal and professional interest in improving my own practice. Conceptually the study draws on Morrow’s (2007, 2009) and various literacy theorists interpretations of the concept of epistemological access, which in this study is about becoming and being a participant in an academic practice by virtue of learning both the knowledge as well as the norms, values and beliefs that constitute the practice. Theoretically and analytically the study draws on Maton’s (2014a) Legitimation Code Theory (LCT) and on various aspects of Bernstein’s (2000) code theory work. Codes are the organising principles or ‘rules of the game’ of practices and code theory is premised on the idea that power and control in education systems manifest themselves through the structural and interactional aspects of educational practices, and therefore have the capacity to include or exclude. Analysing educational practices using code theory enables characterisation of the practices, highlights their underpinning principles, and allows for their effects to be considered. This layered approach to analysis indicates that a critical realist depth ontology serves as an underlabourer to code theory. The desired ‘effect’ of educational practices in this study, is students gaining epistemological access to science, or science disciplines, in higher education. The overall approach is a single, in-depth, qualitative case study with a primary focus on what is legitimated in ISCM educational practices (curriculum, pedagogy, assessment) and how students respond to these practices. A lesser focus is how ex-ISCM students are responding to educational practices in the first-year, first-semester Cell Biology, Chemistry, Earth Sciences and Physics mainstream courses, and whether they are attaining epistemological access. To examine educational practices in ISCM and mainstream courses data from document analysis, interviews, observations and critical reflections are analysed through developing external languages of description. The two LCT code dimensions of Specialisation (what or who specialises a practice) and Semantics (how meaning relates to context and empirical referents) are used to examine curriculum,…
Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection.

BACKGROUND & AIMS Chronic infection with hepatitis B or C virus (HBV or HCV) is a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation of gut microbial products into the systemic circulation might increase because of increased intestinal permeability, bacterial overgrowth, or impaired clearance of microbial products by Kupffer cells. We investigated whether the extent and progression of liver disease in patients with chronic HBV or HCV infection are associated with microbial translocation and subsequent activation of monocytes. METHODS In a retrospective study, we analyzed data from 16 patients with minimal fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) by the limulus amebocyte lysate assay, at presentation and after antiviral treatment. RESULTS Compared with uninfected individuals, HCV- and HBV-infected individuals had higher plasma levels of LPS, intestinal fatty acid binding protein (indicating enterocyte death), sCD14 (produced upon LPS activation of monocytes), and interleukin-6. Portal hypertension, indicated by low platelet counts, was associated with enterocyte death (P=.045 at presentation, P<.0001 after therapy). Levels of sCD14 correlated with markers of hepatic inflammation (P=.02 for aspartate aminotransferase, P=.002 for ferritin) and fibrosis (P<.0001 for γ-glutamyl transpeptidase, P=.01 for alkaline phosphatase, P<.0001 for α-fetoprotein). Compared to subjects with minimal fibrosis, subjects with severe fibrosis at presentation had higher plasma levels of sCD14 (P=.01) and more hepatic CD14+ cells (P=.0002); each increased risk for disease progression (P=.0009 and P=.005, respectively). CONCLUSIONS LPS-induced local and systemic inflammation is associated with cirrhosis and predicts progression to end-stage liver disease in patients with HBV or HCV infection.
The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein

The P2X7 receptor (P2X7R) is a known and powerful activator of the NOD‐like receptor (NLR)P3 inflammasome; however, the underlying pathways are poorly understood. Thus, we investigated the molecular mechanisms involved. The effect of P2X7R expression and activation on NLRP3 expression and recruitment was investigated by Western blot, RT‐PCR, coimmunoprecipitation, and confocal microscopy in microglial mouse cell lines selected for reduced P2X7R expression and in primary cells from P2X7R‐/‐ C57BL/6 mice. We show here that P2X7R activation by ATP (EC50 = 1 mM) or benzoyl‐ATP (EC50 = 300 μM) and P2X7R down‐modulation caused a 2‐ to 8‐fold up‐regulation of NLRP3 mRNA in mouse N13 microglial cells. Moreover, NLRP3 mRNA was also up‐regulated in primary microglial and macrophage cells from P2X7R‐/‐ mice. Confocal microscopy and immunoprecipitation assays showed that P2X7R and NLRP3 closely interacted at discrete subplasmalemmal sites. Finally, P2X7R stimulation caused a transient (3‐4 min) cytoplasmic Ca2+ increase localized to small (2‐3 μm wide) discrete subplasmalemmal regions. The Ca2+ increase drove P2X7R recruitment and a 4‐fold increase in P2X7R/NLRP3 association within 1‐2 min. These data show a close P2X7R and NLRP3 interaction and highlight the role of P2X7R in the localized cytoplasmic ion changes responsible for both NLRP3 recruitment and activation. — Franceschini, A. , Capece, M. , Chiozzi, P., Falzoni, S. , Sanz, J. M. , Sarti, A. C. , Bonora, M. , Pinton, P., Di Virgilio, F. The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J. 29, 2450‐2461 (2015). www.fasebj. org
Efficacy and Safety Extrapolation Analyses for Atomoxetine in Young Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES This extrapolation analysis qualitatively compared the efficacy and safety profile of atomoxetine from Lilly clinical trial data in 6-7-year-old patients with attention-deficit/hyperactivity disorder (ADHD) with that of published literature in 4-5-year-old patients with ADHD (two open-label [4-5-year-old patients] and one placebo-controlled study [5-year-old patients]). METHODS The main efficacy analyses included placebo-controlled Lilly data and the placebo-controlled external study (5-year-old patients) data. The primary efficacy variables used in these studies were the ADHD Rating Scale-IV Parent Version, Investigator Administered (ADHD-RS-IV-Parent:Inv) total score, or the Swanson, Nolan and Pelham (SNAP-IV) scale score. Safety analyses included treatment-emergent adverse events (TEAEs) and vital signs. Descriptive statistics (means, percentages) are presented. RESULTS Acute atomoxetine treatment improved core ADHD symptoms in both 6-7-year-old patients (n=565) and 5-year-old patients (n=37) (treatment effect: -10.16 and -7.42). In an analysis of placebo-controlled groups, the mean duration of exposure to atomoxetine was ∼ 7 weeks for 6-7-year-old patients and 9 weeks for 5-year-old patients. Decreased appetite was the most common TEAE in atomoxetine-treated patients. The TEAEs observed at a higher rate in 5-year-old versus 6-7-year-old patients were irritability (36.8% vs. 3.6%) and other mood-related events (6.9% each vs. <3.0%). Blood pressure and pulse increased in both 4-5-year-old patients and 6-7-year-old patients, whereas a weight increase was seen only in the 6-7-year-old patients. CONCLUSIONS Although limited by the small sample size of the external studies, these analyses suggest that in 5-year-old patients with ADHD, atomoxetine may improve ADHD symptoms, but possibly to a lesser extent than in older children, with some adverse events occurring at a higher rate in 5-year-old patients.
Vancomycin-resistant enterococci in intensive care units: high frequency of stool carriage during a non-outbreak period.

BACKGROUND We aimed to define the epidemiological associations of vancomycin-resistant enterococci (VRE) in intensive care units (ICUs) during a non-outbreak period by examining prevalence, risk factors for colonization, frequency of acquisition, and molecular strain types. DESIGN A prospective cohort design was followed. Consecutive patient admissions to 2 surgical ICUs at a tertiary care hospital were enrolled. The main outcome measures were results of serial surveillance cultures screened for VRE. RESULTS Of 290 patients enrolled, 35 (12%) had colonization with VRE on admission. The VRE colonization or infection had been previously detected by clinical cultures in only 4 of these patients. Using logistic regression, VRE colonization at the time of ICU admission was associated with second- and third-generation cephalosporins (odds ratio [OR] = 6.0, P<.0001), length of stay prior to surgical ICU admission (OR = 1.06, P = .001) greater than 1 prior ICU stay (OR = 9.6, P = .002), and a history of solid-organ transplantation (OR = 3.8, P = .021). Eleven (12.8%) of 78 patients with follow-up cultures acquired VRE. By pulsed-field gel electrophoresis, 2 strains predominated, one of which was associated with an overt outbreak on a non-ICU ward near the end of the study period. CONCLUSIONS Colonization was common and usually not recognized by clinical culture. Most patients who had colonization with VRE and were on the surgical ICU acquired VRE prior to surgical ICU entry. Exposure to second- and third-generation cephalosporins, but not vancomycin, was an independent risk factor for colonization. Prospective surveillance of hospitalized patients may yield useful insights about the dissemination of nosocomial VRE beyond what is appreciated by clinical cultures alone.
The Moderating Role of Age-Group Identification and Perceived Threat on Stereotype Threat among Older Adults

Although research has shown that older adults are negatively affected by aging stereotypes, relatively few studies have attempted to identify those older adults who may be especially susceptible to these effects. The current research takes steps toward identifying older adults most susceptible to the effects of stereotype threat and investigates the consequence of stereotype threat on the well-being of older adults. Older adults were tested on their recall of a prose passage under normal or stereotype threatening conditions. Memory decrements for those in the threat condition were moderated by perceived stereotype threat such that greater decrements were seen for those who reported greater perceived threat. A similar pattern was observed for negative emotion, such that those in the threat condition who reported higher perceptions of threat experienced a greater decrease in positive emotions. Age group identification also proved to be an important factor, with the strongly identified performing worse than the weakly identified. As well, high age-group identification buffered some of the negative affective consequences associated with stereotype threat, which is consistent with some models of coping with stigma.
Weekly high‐dose calcitriol and docetaxel in patients with metastatic hormone‐refractory prostate cancer previously exposed to docetaxel

To evaluate the activity and tolerability of weekly high‐dose calcitriol and docetaxel in patients with metastatic hormone‐refractory prostate cancer (HRPC) previously exposed to docetaxel, as patients who progress after docetaxel treatment might be considered for second‐line chemotherapy, but with no standard salvage therapy available we hypothesised that high‐dose calcitriol might restore sensitivity to chemotherapy.
Peroxisome proliferator-activated receptor gamma polymorphisms affect systemic inflammation and survival in end-stage renal disease patients starting renal replacement therapy.

BACKGROUND Inflammation may contribute to the markedly increased cardiovascular morbidity and mortality in end-stage renal disease (ESRD). However, the prevalence of inflammation varies in different ESRD populations. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is an important nuclear signaling protein that may regulate inflammatory response, and recent studies have revealed genetic polymorphisms that have significant effect on PPAR-gamma signaling. The aim of this study was to clarify whether the PPAR-gamma 161C/T and PPAR-gamma2 Pro12Ala single-nucleotide polymorphisms (SNPs) influence the inter-individual variance of inflammation and mortality in ESRD patients. METHODS The present prospective study included 229 incident Caucasian ESRD patients (62% males) just prior to starting renal replacement therapy and 207 healthy controls (62% males). Blood samples were taken for measuring systemic inflammatory (CRP, TNF-alpha, IL-6) and nutritional (S-albumin) parameters. The presence of diabetes mellitus, malnutrition (subjective global assessment (SGA)) and cardiovascular disease (CVD) were also assessed. Genotyping of the two PPAR-gamma SNPs was performed using Pyrosequencing. During follow-up (1621+/-63 days), both all-cause and CVD-mortality were investigated. RESULTS ESRD patients had a higher prevalence of both the PPAR-gamma 161 CC and PPAR-gamma2 Pro12Pro genotypes than the general population (p<0.01). Whereas the Pro12Pro genotype was associated with higher median serum levels of both hs-CRP (p<0.05) and TNF-alpha (p<0.01) the 161CC genotype was associated with a significantly higher (6.6 mg/L versus 3.3 mg/L; p<0.01) median hs-CRP level. Following adjustment for age, gender, SGA and CVD a significantly higher mortality rate was observed in patients with the Pro12Pro genotype. CONCLUSION This study demonstrates significant differences in PPAR-gamma genotype distribution between ESRD patients and healthy controls. Furthermore, as the PPAR-gamma2 Pro12Pro genotype was associated with both higher levels of biomarkers of inflammation as well as shorter survival, genetic polymorphisms seem to play a role in determining systemic inflammatory status and outcome in this patient group.
Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma.

PURPOSE Germline mutations of the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) predispose to malignant paraganglioma (PGL). Timely and accurate localization of these aggressive tumors is critical for guiding optimal treatment. Our aim is to evaluate the performance of functional imaging modalities in the detection of metastatic lesions of SDHB-associated PGL. PATIENTS AND METHODS Sensitivities for the detection of metastases were compared between [18F]fluorodopamine ([18F]FDA) and [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), iodine-123- (123I) and iodine-131 (131I) -metaiodobenzylguanidine (MIBG), 111In-pentetreotide, and Tc-99m-methylene diphosphonate bone scintigraphy in 30 patients with SDHB-associated PGL. Computed tomography (CT) and magnetic resonance imaging (MRI) served as standards of reference. RESULTS Twenty-nine of 30 patients had metastatic lesions. In two patients, obvious metastatic lesions on functional imaging were missed by CT and MRI. Sensitivity according to patient/body region was 80%/65% for 123I-MIBG and 88%/70% for [18F]FDA-PET. False-negative results on 123I-MIBG scintigraphy and/or [18F]FDA-PET were not predicted by genotype or biochemical phenotype. [18F]FDG-PET yielded a by patient/by body region sensitivity of 100%/97%. At least 90% of regions that were false negative on 123I-MIBG scintigraphy or [18F]FDA-PET were detected by [18F]FDG-PET. In two patients, 111In-pentetreotide scintigraphy detected liver lesions that were negative on other functional imaging modalities. Sensitivities were similar before and after chemotherapy or 131I-MIBG treatment, except for a trend toward lower post- (60%/41%) versus pretreatment (80%/65%) sensitivity of 123I-MIBG scintigraphy. CONCLUSION With a sensitivity approaching 100%, [18F]FDG-PET is the preferred functional imaging modality for staging and treatment monitoring of SDHB-related metastatic PGL.
Extracorporeal liver support

Purpose of reviewThe mortality in patients suffering from liver failure decreased in line with medical progress over the past decades. However, it still remains unacceptably high and liver transplantation still provides the only definite treatment for many patients. The goal of extracorporeal liver support systems is to improve the clinical condition of patients waiting for liver transplantation and/or enhance the regeneration of native injured liver. Nonbiological liver support systems with pure detoxification and biological liver support systems with assumed synthesis and metabolism in addition to detoxification are currently under clinical investigation. Since patient survival is the most significant outcome parameter, we focus in this review on prospective randomized trials with survival rate as primary outcome parameter. Recent findingsAlthough a short-term outcome benefit in patients with acute-on-chronic liver failure was shown in some of these trials, long-term outcome has not been improved significantly with either of the support systems. In spite of more favourable but yet limited data in patients with acute liver failure, it is too early to draw definite conclusions. SummaryThe future development of liver support systems may provide different combinations of new adsorbents, integrated regional citrate anticoagulation and eventual substitution of irreversibly damaged albumin.