Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining quality of perioperative care by statistical process control of adverse outcomes.

Background: Through peer review, we separated the contributions of system error and human (anesthesiologist) error to adverse perioperative outcomes. In addition, we monitored the quality of our perioperative care by statistically defining a predictable rate of adverse outcome dependent on the system in which practice occurs and respondent to any special causes for variation. Methods: Traditional methods of identifying human errors using peer review were expanded to allow identification of system errors in cases involving one or more of the anesthesia clinical indicators recommended in 1992 by the joint Commission on Accreditation of Healthcare Organizations. Outcome data also were subjected to statistical process control analysis, an industrial method that uses control charts to monitor product quality and variation. Results: Of 13,389 anesthetics, 110 involved one or more clinical indicators of the joint Commission on Accreditation of Healthcare Organizations. Peer review revealed that 6 of 110 cases involved two separate errors. Of these 116 errors, 9 (7.8%) were human errors and 107 (92.2%) were system errors. Attribute control charts demonstrated all indicators, excepting one (fulminant pulmonary edema), to be in statistical control. Conclusions: The major determinant of our patient care quality is the system through which services are delivered and not the individual anesthesia care provider. Outcome of anesthesia services and perioperative care is in statistical control and therefore stable. A stable system has a measurable, communicable capability that allows description and prediction of the quality of care we provide on a monthly basis
Chemorepellent Semaphorin 3E Negatively Regulates Neutrophil Migration In Vitro and In Vivo

Neutrophil migration is an essential step in leukocyte trafficking during inflammatory responses. Semaphorins, originally discovered as axon guidance cues in neural development, have been shown to regulate cell migration beyond the nervous system. However, the potential contribution of semaphorins in the regulation of neutrophil migration is not well understood. This study examines the possible role of a secreted chemorepellent, Semaphorin 3E (Sema3E), in neutrophil migration. In this study, we demonstrated that human neutrophils constitutively express Sema3E high-affinity receptor, PlexinD1. Sema3E displayed a potent ability to inhibit CXCL8/IL-8–induced neutrophil migration as determined using a microfluidic device coupled to real-time microscopy and a transwell system in vitro. The antimigratory effect of Sema3E on human neutrophil migration was associated with suppression of CXCL8/IL-8–mediated Ras-related C3 botulinum toxin substrate 1 GTPase activity and actin polymerization. We further addressed the regulatory role of Sema3E in the regulation of neutrophil migration in vivo. Allergen airway exposure induced higher neutrophil recruitment into the lungs of Sema3e−/− mice compared with wild-type controls. Administration of exogenous recombinant Sema3E markedly reduced allergen-induced neutrophil recruitment into the lungs, which was associated with alleviation of allergic airway inflammation and improvement of lung function. Our data suggest that Sema3E could be considered an essential regulatory mediator involved in modulation of neutrophil migration throughout the course of neutrophilic inflammation.
A New RNA-Based Adjuvant Enhances Virus-Specific Vaccine Responses by Locally Triggering TLR- and RLH-Dependent Effects

Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Furthermore, such sera neutralized influenza virus, whereas this effect was not detected upon vaccination with the subunit vaccine alone. Similarly, upon vaccination with virus-like particles displaying vesicular stomatitis virus G protein, RNAdjuvant promoted the formation of virus-specific IgG2b/c and enhanced neutralizing IgG responses to an extent that mice were protected against lethal virus infection. RNAdjuvant induced dendritic cells to upregulate activation markers and produce IFN-I. Although these effects were strictly TLR7 dependent, RNAdjuvant-mediated augmentation of vaccine responses needed concurrent TLR and RIG-I–like helicase signaling. This was indicated by the absence of the adjuvant effect in vaccinated MyD88−/−Cardif−/− mice, which are devoid of TLR (with the exception of TLR3) and RIG-I–like helicase signaling, whereas in vaccinated MyD88−/− mice the adjuvant effect was reduced. Notably, i.m. RNAdjuvant injection induced local IFN-I responses and did not induce systemic effects, implying good tolerability and a favorable safety profile for RNAdjuvant.
Stroke Units: An Evidence Based Approach.

Stroke Units: An Evidence Based Approach. Edited by peter langhorne and martin dennis. (Pp112, £25.00). Published by BMJ Books, London 1998. ISBN 0-7279-1211-9. Ever since the landmark overview “Do stroke units save lives? ” the momentum behind the organisation of stroke sevices has inexorably increased. Within this concise paperback of seven chapters and 112 pages, written in the main by Langhorne and …
Comment on “A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood”

W e read with interest the article by Dan et al. (1) published in the Journal of Immunology online on June 24, 2016. In this article, the authors demonstrate that the OX40 assay, a method developed in our laboratory for the study of Ag-specific CD4 T cells, can also be used for the detection of T follicular helper cells in tonsillar cells. We were interested to see that the authors have independently replicated our 2012 publication that showed the 44 h OX40 assay was equivalent to the QuantiFERON TB Gold assay for the detection of CD4 T cell responses to Mycobacterium tuberculosis Ags (2). Similarly, we also note that in a parallel publication, the same group has used the OX40 assay to detect Ag-specific CD4 T cells, including PD-1 CXCR5 GC Tfh cells, in lymph node and peripheral blood from rhesus macaques (3). This both confirms and extends our previous findings that the OX40 assay could be used to detect CD4 T cell responses to SEB and SIV Ag in lymph node cells and peripheral blood from pigtail macaques (4, 5). However, we note that the adaptation of the assay to study human tonsils shows substantially increased background (1–4% of CD4 T cells) compared with our whole blood OX40 assay method where the background is ,0.02% (Fig. 1). This is our experience as well and likely reflects the different physiological milieu from which the cells are derived, with greater cell-to-cell contact and Ag presentation occurring in lymphoid tissue in the period immediately prior to sampling. Further, our original data from PBLs clearly shows that there is no significant proliferation or apoptosis during the 48 h incubation period (6), an observation we have confirmed during the optimization of the assay for a range of stimulating Ags in humans and macaques (4–9) and (Fig. 2). It is possible that the incubation period for the assay requires optimization depending on the source of the cells. The data from Dan et al. (1) extend the utility of the OX40 assay by validating its use for detecting Tfh cells specific for a bacterial Ag in lymphoid tissue. The OX40 assay has now been shown to be suitable for detecting all Agspecific CD4 T cells, including regulatory and Tfh subsets (8, 10), for a range of viral, bacterial, fungal, commensal, dietary and self-antigens [(7–11) and L. Cook, J.J. Zaunders, A.D. Kelleher, and M.K. Levings, unpublished data) providing a simple and robust method to obtain viable Ag-specific cell populations for functional analysis even when present at low levels (2, 7, 8). Furthermore, the frequency and phenotype of these responses have been associated with the effectiveness of immune responses and response to therapy in several diseases (7, 10, 11).
Glucose-Dependent Insulinotropic Polypeptide Receptor Deficiency Leads to Impaired Bone Marrow Hematopoiesis

The bone marrow (BM) contains controlled specialized microenvironments, or niches, that regulate the quiescence, proliferation, and differentiation of hematopoietic stem and progenitor cells (HSPC). The glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone that mediates postprandial insulin secretion and has anabolic effects on adipose tissue. Previous studies demonstrated altered bone microarchitecture in mice deficient for GIP receptor (Gipr−/−), as well as the expression of high-affinity GIP receptor by distinct cells constructing the BM HSPC niche. Nevertheless, the involvement of GIP in the process of BM hematopoiesis remains elusive. In this article, we show significantly reduced representation and proliferation of HSPC and myeloid progenitors in the BM of Gipr−/− mice. This was further manifested by reduced levels of BM and circulating differentiated immune cells in young and old adult mice. Moreover, GIP signaling was required for the establishment of supportive BM HSPC niches during HSPC repopulation in radioablated BM chimera mice. Finally, molecular profiling of various factors involved in retention, survival, and expansion of HSPC revealed significantly lower expression of the Notch-receptor ligands Jagged 1 and Jagged 2 in osteoblast-enriched bone extracts from Gipr−/− mice, which are important for HSPC expansion. In addition, there was increased expression of CXCL12, a factor important for HSPC retention and quiescence, in whole-BM extracts from Gipr−/− mice. Collectively, our data suggest that the metabolic hormone GIP plays an important role in BM hematopoiesis.
Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14+ CD1c+ Monocytes

Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor (TSLPR) complex, a heterodimer composed of TSLPR and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLPR complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is poorly defined. We demonstrate that TSLP enhances human CD14+ monocyte CCL17 production in response to LPS and IL-4. Surprisingly, only a subset of CD14+ CD16− monocytes, TSLPR+ monocytes (TSLPR+ mono), expresses TSLPR complex upon LPS stimulation in an NF-κB– and p38-dependent manner. Phenotypic, functional, and transcriptomic analysis revealed specific features of TSLPR+ mono, including higher CCL17 and IL-10 production and increased expression of genes with important immune functions (i.e., GAS6, ALOX15B, FCGR2B, LAIR1). Strikingly, TSLPR+ mono express higher levels of the dendritic cell marker CD1c. This evidence led us to identify a subset of peripheral blood CD14+ CD1c+ cells that expresses the highest levels of TSLPR upon LPS stimulation. The translational relevance of these findings is highlighted by the higher expression of TSLPR and CD127 mRNAs in monocytes isolated from patients with Gram-negative sepsis compared with healthy control subjects. Our results emphasize a phenotypic and functional heterogeneity in an apparently homogeneous population of human CD14+ CD16− monocytes and prompt further ontogenetic and functional analysis of CD14+ CD1c+ and LPS-activated CD14+ CD1c+ TSLPR+ mono.
Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti–DENV NS1 Ab–mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti–DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host–cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease.
Validación de la versión española del cuestionario sobre la práctica basada en la evidencia en enfermería

Fundamento. La falta de instrumentos adecuados impide conocer la competencia de los profesionales en la toma de decisiones basadas en la evidencia e identificar areas de mejora en las que intervenir con estrategias "ad hoc". El objetivo de la investigacion es validar en el entorno espanol del Evidence-Based Practice Questionnaire (EBPQ) (Upton y Upton, 2006). Metodos. Se llevo a cabo un estudio multicentrico, descriptivo y transversal de validacion psicometrica. Se siguio un proceso de traduccion-retrotraduccion segun los estandares habituales. Se contrasto el modelo de medida del cuestionario, replicando la estructura original anglosajona mediante analisis factorial exploratorio (AFE) y confirmatorio (AFC), incluyendo analisis de la fiabilidad de los factores. Resultados. Tanto el AFE (57,545% de la varianza total explicada) como el AFC (chi²=2359,9555; gl=252; p < 0,0001; RMSEA=0,1844; SRMR=0,1081) han detectado problemas en los items 7, 16, 22, 23 y 24 sobre la version original trifactorial del EBPQ. Una version reducida de 19 items presenta una estructura factorial exploratoria adecuada (62,29% de varianza total explicada), aunque el AFC no mostro adecuacion, fue significativamente mejor que en la version original (chi²=673.1261; gl=149; p < 0,0001; RMSEA=0,1196; SRMR=0,0648). Conclusiones: El modelo trifactorial (EBPQ-19) ha obtenido suficiente evidencia empirica para su sustentacion y puede ser aplicado en nuestro medio, aunque los resultados invitan a refinar el factor "actitud", mediante el contraste en muestras en otros contextos y con mayor heterogeneidad de perfiles profesionales.
Dependence of Glomerulonephritis Induction on Novel Intraglomerular Alternatively Activated Bone Marrow–Derived Macrophages and Mac-1 and PD-L1 in Lupus-Prone NZM2328 Mice

Glomerular damage mediated by glomerulus-infiltrating myeloid-derived cells is a key pathogenic event in lupus nephritis (LN), but the process is poorly understood. Confocal microscopy of kidney sections and flow cytometry analysis of glomerular cells from magnetic bead–purified glomeruli have identified glomerulus-infiltrating leukocyte populations in NZM2328 (NZM) lupus-prone mice with spontaneous chronic glomerulonephritis (GN) and anti–glomerular basement membrane-induced nephritis. The occurrence of a major glomerulus-infiltrating CD11b+F4/80−I-A− macrophage population exhibiting the markers programmed death ligand-1 (PD-L1), Mac-2, and macrophage mannose receptor (CD206) and producing Klf4, Il10, Retnla, Tnf, and Il6 mRNA, which are known to be expressed by alternatively activated (M2b) macrophages, correlated with proteinuria status. In NZM mice with spontaneous LN, glomerular macrophage infiltration is predominant. CD11b+F4/80−I-A− intraglomerular macrophages and polymorphonuclear neutrophils (PMN) are important in inducing GN, as anti-CD11b and –ICAM-1 mAb inhibited both proteinuria and macrophage and PMN infiltration. The predominant and high expression of PD-L1 by CD11b+F4/80−I-A− glomerular macrophages in kidneys of mice with GN and the inhibition of proteinuria by anti–PD-L1 mAb supported the pathogenic role of these macrophages but not the PD-L1− PMN in GN development and in inducing podocyte damage. In NZM mice with spontaneous chronic GN and severe proteinuria, few glomerulus-infiltrating PMN were found, leaving macrophages and, to a less extent, dendritic cells as the major infiltrating leukocytes. Taken together, these data support the important pathogenic effect of CD11b+F4/80−I-A− M2b-like glomerulus-infiltrating macrophages in LN and reinforce macrophages as a promising target for GN treatment.
When and how to measure lipids and their role in CHD risk prediction

Accurate lipid and lipoprotein measurements, control of pre-analytical factors and consideration of biological variability are required for the reliable assessment of coronary heart disease (CHD) risk and the management of dyslipidaemia. Inclusion of high density lipoprotein-cholesterol, in addition to total cholesterol, in risk calculations is preferred to attain good sensitivity and specificity. Although the strong and independent association of triglyceride with CHD has been confirmed, its large biological variation limits its utility as a risk factor or primary treatment target. A fasting profile including triglyceride is essential however for consideration of genetic and secondary causes of dyslipidaemia and decisions on therapeutic intervention.
IDENTIFICATION OF HOST MATERIAL FROM CROPS AND WHOLE BODIES OF Protophormia terraenovae (R-D) (DIPTERA) LARVAE, PUPAE, AND ADULTS, AND THE IMPLICATIONS FOR FORENSIC STUDIES

ABSTRACT Larvae of Diptera are used routinely in forensic entomology to estimate accurately the post mortem interval. These applications require a detailed understanding of insect growth rates and insect succession profiles under different climactic conditions and geographical locations. There may be times when larvae may have been removed from a single food source or the corpse has been moved from one location to another, confounding the interpretation of the entomological data. We report here a study that evaluates the time period during which a food source can be detected in larvae of Protophormia terraenovae. We could detect the food source (pork or chicken liver) that larvae had ingested from early second instar to late third instar larvae. No detection was possible in pupae or adults. When larvae were transferred from one food source to another, the primary source was detectable for only 8–12 hours after transfer, whereas it was detectable for 12 hours in starved larvae. In most studies that use insects to estimate PMI, investigators collect larvae directly from the corpse. In cases where there have been significant disturbances, investigators must understand the changes in insect dieting and development that may take place.
Assessment of internet gaming disorder in clinical research: Past and present perspectives

Abstract Internet Gaming Disorder (IGD) has recently received nomenclatural recognition from official medical bodies as a potential mental health disorder, despite evident variability and inconsistencies in its core conceptualization and psychometric assessment. Research on gaming addiction dates back to the 1970s, and important changes in the field have occurred, especially in terms of definition and conceptualization of the phenomenon, which resulted in a multiplicity of strategies in the assessment of IGD via inconsistent criteria or psychometric tools. In the present review, the authors argue how the adoption of inconsistent criteria and psychometric tools for assessing IGD has negatively influenced the field. Furthermore, this review provides an overview of how the field evolved in terms of its historical developments, current definitions and frameworks, developments in the neurobiological research, psychometric assessment, and emerging trends in the assessment of gaming addiction. Finally, the paper provides information on alternative emerging methods for assessing IGD via sound psychometric tools based on updated and officially recognized conceptualization of the phenomenon of IGD.
Neutrophil Microparticles Deliver Active Myeloperoxidase to Injured Mucosa To Inhibit Epithelial Wound Healing

Neutrophil (PMN) infiltration of the intestinal mucosa often leads to severe epithelial injury; however, how this process occurs is unclear. This article describes a novel mechanism whereby membrane-derived microparticles released by tissue infiltrating PMNs (PMN-MPs) serve as shuttles to protect and deliver active mediators to locally modulate cellular function during inflammation. Specifically, myeloperoxidase (MPO), which is abundantly expressed in PMN azurophilic granules and is used for microbial killing, was found to be mobilized to the PMN surface and subsequently released in association with PMN-MPs upon PMN activation and binding to intestinal epithelial cells (IECs). The enzymatic activity of PMN-MP–associated MPO was enhanced compared with soluble protein, leading to potent inhibition of wound closure following PMN-MP binding to IECs. Importantly, localized microinjection of PMN-MPs into wounded colonic mucosa was sufficient to impair epithelial wound healing in vivo. PMN-MP/MPO–dependent inhibition of IEC wound healing was due to impaired IEC migration and proliferation, resulting from impeded actin dynamics, cell spreading, and cell cycle arrest. Thus, our findings provide new insight into mechanisms governing PMN-induced tissue injury and implicate PMN-MPs and MPO as important regulators of cellular function.
A genome-wide association study of chronic obstructive pulmonary disease in Hispanics.

RATIONALE Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent. OBJECTIVES We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations. METHODS We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the top single-nucleotide polymorphisms in an independent Hispanic cohort in New Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior findings from genome-wide studies in non-Hispanic populations in Hispanic cohorts. MEASUREMENTS AND MAIN RESULTS We found no genome-wide significant association with COPD in our metaanalysis of Costa Rica and MESA. After combining the top results from this metaanalysis with those from our replication study in the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms approaching genome-wide significance for an association with COPD. The first (rs858249, combined P value = 6.1 × 10(-8)) is near the genes KLHL7 and NUPL2 on chromosome 7. The second (rs286499, combined P value = 8.4 × 10(-8)) is located in an intron of DLG2. The two most significant single-nucleotide polymorphisms in FAM13A from a previous genome-wide study in non-Hispanics were associated with COPD in Hispanics. CONCLUSIONS We have identified two novel loci (in or near the genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic populations.