Search

OBJECTIVE: There is widespread overuse of antibiotics in neonatal intensive care units (NICUs). The objective of this study was to safely reduce antibiotic use in participating NICUs by targeting early-onset sepsis (EOS) management. STUDY DESIGN: Twenty-eight NICUs participated in this statewide multicenter antibiotic stewardship quality improvement collaborative. The primary aim was to reduce the total monthly mean antibiotic utilization rate (AUR) by 25% in participant NICUs. RESULT: Aggregate AUR was reduced by 15.3% (p

This study examines the reliability of parental concern (PC) as an indicator for mental disorders in preschool-aged children in a clinical setting, aiming to establish sensitivity and specificity, evaluate PC's predictive value for specific diagnoses, and explore the influence of child age on predictions. The sample comprises 574 children referred to child psychiatry services (mean age 47 months, 73% boys). Analyses of sensitivity and specificity for five distinct PC were conducted, while logistic regressions explored the predictive value of PC for corresponding diagnoses, accounting for child age. Language-related concerns emerged as the most frequent and accurate. Sensitivity ranged from 7% to 72%, while specificity ranged from 57% to 97%. PC demonstrated predictive validity for their corresponding diagnoses, except for motor disorders. Child age did not substantially influence these predictions. Findings suggest that systematically incorporating PC into the assessment process for preschool-aged children consulting in child psychiatry is warranted.

BackgroundSingle photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique.MethodsAccuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio.ResultsSPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P0.05 for all).ConclusionsMBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation.

Background: Some data call into question the persistence of developmental language disorders (DLDs) identified during the preschool period. For this reason, speech-language pathologists (SLPs) often reassess children. However, it is unclear if the instability of the profiles documented in community sample studies is present in children referred to specialized clinics. Given the scarcity of SLP resources, is re-evaluating the language skills of these children a good use of clinical time? Aim: To examine the stability of the findings from two SLP assessments in a sample of Canadian preschool children referred to a tertiary clinic between the ages of 2 and 6 years. It was hypothesized that children under the age of 4 years at first assessment and children with less severe initial deficits would show less stability of DLD diagnosis. Methods & Procedures: The clinical files of children referred to an early childhood psychiatric clinic in Canada were reviewed. For 149 children with two SLPs assessment reports, persistence of language deficits was documented and tested with McNemar's statistics. Differences between preschoolers under the age of 4 versus 4 years and over, as well as between mildly and severely impaired children, were examined. Outcomes & Results: High level of agreement (94%) and McNemar's test (p = 0.180) supported the stability of initial diagnosis. The stability for children assessed before the age of 4 (n = 64) was 100%, and was significantly different from older children's (n = 85) stability of 89% (Fisher's exact test, p = 0.01; bilateral). The stability for children with mild impairments (n = 18) was 78%, which was significantly lower than the stability (97%) in children with severe impairments (n = 114) (Fisher's exact test, p = 0.007; bilateral). Conclusions & Implications: No instability of language status was observed in children assessed before 4 years of age, which could be related to the significant severity of the difficulties that children in this age group presented and be specific to this type of clinical sample. The great stability of language status observed in preschoolers referred to a specialized clinic suggests that clinicians should limit reassessments to devote available resources to intervention efforts.

Toxin B (TcdB) is a major exotoxin responsible for diseases associated with Clostridioides difficile infection. Its sequence variations among clinical isolates may contribute to the difficulty in developing effective therapeutics. Here, we investigate receptor-binding specificity of major TcdB subtypes (TcdB1 to TcdB12). We find that representative members of subtypes 2, 4, 7, 10, 11, and 12 do not recognize the established host receptor, frizzled proteins (FZDs). Using a genome-wide CRISPR-Cas9-mediated screen, we identify tissue factor pathway inhibitor (TFPI) as a host receptor for TcdB4. TFPI is recognized by a region in TcdB4 that is homologous to the FZD-binding site in TcdB1. Analysis of 206 TcdB variant sequences reveals a set of six residues within this receptor-binding site that defines a TFPI binding-associated haplotype (designated B4/B7) that is present in all TcdB4 members, a subset of TcdB7, and one member of TcdB2. Intragenic micro-recombination (IR) events have occurred around this receptor-binding region in TcdB7 and TcdB2 members, resulting in either TFPI- or FZD-binding capabilities. Introduction of B4/B7-haplotype residues into TcdB1 enables dual recognition of TFPI and FZDs. Finally, TcdB10 also recognizes TFPI, although it does not belong to the B4/B7 haplotype, and shows species selectivity: it recognizes TFPI of chicken and to a lesser degree mouse, but not human, dog, or cattle versions. These findings identify TFPI as a TcdB receptor and reveal IR-driven changes on receptor-specificity among TcdB variants.

Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5+ ISCs, the most well-defined ISC pool, but Bmi1-GFP+ cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP+ cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1+ cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo. Single-cell mRNA-seq revealed two subsets of Prox1-GFP+ cells, one of which resembled mature EE cells while the other displayed low-level EE gene expression but co-expressed tuft cell markers, Lgr5 and Ascl2, reminiscent of label-retaining secretory progenitors. Our data suggest that the EE lineage, including mature EE cells, comprises a reservoir of homeostatic and injury-inducible ISCs, extending our understanding of cellular plasticity and stemness.

BACKGROUND: Drp1 (dynamin-related protein 1), a large GTPase, mediates the increased mitochondrial fission, which contributes to hyperproliferation of pulmonary artery smooth muscle cells in pulmonary arterial hypertension (PAH). We developed a potent Drp1 GTPase inhibitor, Drpitor1a, but its specificity, pharmacokinetics, and efficacy in PAH are unknown. METHODS: Drpitor1a's ability to inhibit recombinant and endogenous Drp1 GTPase was assessed. Drpitor1a's effects on fission were studied in control and PAH human pulmonary artery smooth muscle cells (hPASMC) and blood outgrowth endothelial cells (BOEC). Cell proliferation and apoptosis were studied in hPASMC. Pharmacokinetics and tissue concentrations were measured following intravenous and oral drug administration. Drpitor1a's efficacy in regressing monocrotaline-PAH was assessed in rats. In a pilot study, Drpitor1a reduced PA remodeling only in females. Subsequently, we compared Drpitor1a to vehicles in control and monocrotaline-PAH females. RESULTS: Drp1 GTPase activity was increased in PAH hPASMC. Drpitor1a inhibited the GTPase activity of recombinant and endogenous Drp1 and reversed the increased fission, seen in PAH hPASMC and PAH BOEC. Drpitor1a inhibited proliferation and induced apoptosis in PAH hPASMC without affecting electron transport chain activity, respiration, fission/ fusion mediator expression, or mitochondrial Drp1 translocation. Drpitor1a did not inhibit proliferation or alter mitochondrial dynamics in normal hPASMC. Drpitor1a regressed monocrotaline-PAH without systemic vascular effects or toxicity. CONCLUSIONS: Drpitor1a is a specific Drp1 GTPase inhibitor that reduces mitochondrial fission in PAH hPASMC and PAH BOEC. Drpitor1a reduces proliferation and induces apoptosis in PAH hPASMC and regresses monocrotaline-PAH. Drp1 is a therapeutic target in PAH, and Drpitor1a is a potential therapy with an interesting therapeutic sexual dimorphism. [ABSTRACT FROM AUTHOR]

Given the powerful influence of past school experiences on the ways in which future teachers decide to teach, it is important to help preservice teachers more deliberately and critically explore the implications of those influences. This study grew out of an assignment in which 38 secondary education majors were asked to describe high school teachers they remember as being their favorite teachers and their most effective teachers. There was some overlap between the categories, but more often than not teachers who were considered "favorites" during high school were now seen as having "defaulted on their responsibility to educate and supervise, to open minds and challenge ... students." Although the responses yielded 35 different characteristics of effective teachers, three were dominant: their passion or enthusiasm for both teaching and the subject matter, their concern for the learning of all students, and their knowledge of subject matter.

Educators have long operated under the assumption that principals have a significant effect on schools as well as the teachers who work there. These claims have been supported through a number of recent studies. According to these studies, principals have the potential to influence conditions within schools, and their influence can reach as far as actual student outcomes. Further, Orr and Orphanos (2007) determined that leadership preparation can significantly influence the way leaders lead. Therefore, universities' innovative leadership preparation programs can influence student outcomes as well. Leadership programs across the country are changing to reflect the rhetoric of current NCLB reform narratives. However, this shift is not only problematic for the preparation of future leaders, but, by virtue of the fact that these leaders will have such an influence on schools, the changes will also have a damaging effect on teachers and, ultimately, on the kinds of authentic outcomes one should seek for students. Therefore, stakeholders in leadership preparation are actually instrumental in perpetuating the problems of current prescribed reforms. Said differently, by eschewing theory within leadership preparation programs and by tethering themselves to the pole of use (when said use is exclusively raising test scores), this author contends that stakeholders in leadership preparation enslave themselves--and the students they serve--to a narrow and misguided purpose for schools.

The story of Van Gogh and Gauguin's work together offers interesting points to consider regarding collegial inquiry among educators. This manuscript uses their story, as well as the works of Dewey, Sch?n, and Sennett, to explore dimensions of collegial relationships and how collegiality may promote greater degrees of inquiry among teachers. It concludes that four levels of mutuality are prerequisites for upholding democratic ideals in a school that is a community of inquiry.

Two social media posts (Highland, 2015; Johnson, 2015) about the authenticity of women's experiences in the outdoors fueled an intense dialogue among the authors of this paper. These posts sparked healthy debate, and we asked ourselves, "Why does our apparel, our aesthetic appeal, our physicality, or even our motivation become subject to critique and judgment?" The burgeoning use of social media, in particular the use of Instagram and Facebook to curate a public self, has provided the catalyst for our study. This paper explores the use of online presence by women in the outdoors and examines how social media is portraying those women. In particular, we examined the authenticity of Instagram and Facebook in representing identities. We also interrogated the potential of social media to contribute to the commodification and aestheticization of what it means to be a woman in the outdoors, using current social media literature as a point of departure and Goffman (1959) as a theoretical lens. Findings were mixed; some images perpetuated the aestheticization of women outdoors, whereas others provided inspiring, strength-based portrayals. Such findings implicate the unremitting need to deconstruct negative aspects of social media images of women in the outdoors and develop a new lens to (a) assess the positive aspects of social media images of women in the outdoors, (b) counteract the negative self-perceptions generated by mainstream media images, and (c) allow for positive self-representation.

Abstract Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a "roadmap" for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH.