Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence

Background: Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI. Methods: The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented. Results: The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI. Conclusions: The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit. Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II)

The Photo Essay: A Visual Research Method for Educating Obstetricians and Other Health Care Professionals

When it comes to issues related to low-income women seeking early, adequate, or continuous prenatal ca re, the public health and medical communities continue to tell women to take responsibility for their actions. Rarely are messages aimed at providers. To help physicians see how factors in their offices and clinics can affect service utilization, the photo essay, a visual qualitative research strategy was developed using low- income minority and disenfranchised women who had recently given birth or were near to giving birth. Eight photo essays were completed. Together, the narratives, in collaboration with the photos, provided an opportunity for physicians to hear and observe women, as consumers, as they expanded their descriptions of their prenatal care experience

Genome Sequences of 18 Salmonella enterica Serotype Hadar Strains Collected from Patients in the United States

Despite being linked to a number of recent poultry-associated outbreaks in the United States, few reference genomes are available for Salmonella enterica serotype Hadar. Here, we address this need by reporting 18 Salmonella Hadar genomes from samples collected from patients in the United States between 2014 and 2020

The Loss of Species: Mangrove Extinction Risk and Geographic Areas of Global Concern

Mangrove species are uniquely adapted to tropical and subtropical coasts, and although relatively low in number of species, mangrove forests provide at least US $1.6 billion each year in ecosystem services and support coastal livelihoods worldwide. Globally, mangrove areas are declining rapidly as they are cleared for coastal development and aquaculture and logged for timber and fuel production. Little is known about the effects of mangrove area loss on individual mangrove species and local or regional populations. To address this gap, species-specific information on global distribution, population status, life history traits, and major threats were compiled for each of the 70 known species of mangroves. Each species' probability of extinction was assessed under the Categories and Criteria of the IUCN Red List of Threatened Species. Eleven of the 70 mangrove species (16%) are at elevated threat of extinction. Particular areas of geographical concern include the Atlantic and Pacific coasts of Central America, where as many as 40% of mangroves species present are threatened with extinction. Across the globe, mangrove species found primarily in the high intertidal and upstream estuarine zones, which often have specific freshwater requirements and patchy distributions, are the most threatened because they are often the first cleared for development of aquaculture and agriculture. The loss of mangrove species will have devastating economic and environmental consequences for coastal communities, especially in those areas with low mangrove diversity and high mangrove area or species loss. Several species at high risk of extinction may disappear well before the next decade if existing protective measures are not enforced

The loss of species: mangrove extinction risk and failure of critical exosystem services

Mangrove species are uniquely adapted to tropical and subtropical coasts, and although relatively low in number of species, mangrove forests provide at least US $1.6 billion each year in ecosystem services and support coastal livelihoods worldwide. Globally, mangrove areas are declining rapidly as they are cleared for coastal development and aquaculture and logged for timber and fuel production. Little is known about the effects of mangrove area loss on individual mangrove species and local or regional populations. To address this gap, species-specific information on global distribution, population status, life history traits, and major threats were compiled for each of the 70 known species of mangroves. Each species\u27 probability of extinction was assessed under the Categories and Criteria of the IUCN Red List of Threatened Species. Eleven of the 70 mangrove species (16%) are at elevated threat of extinction. Particular areas of geographical concern include the Atlantic and Pacific coasts of Central America, where as many as 40% of mangroves species present are threatened with extinction. Across the globe, mangrove species found primarily in the high intertidal and upstream estuarine zones, which often have specific freshwater requirements and patchy distributions, are the most threatened because they are often the first cleared for development of aquaculture and agriculture. The loss of mangrove species will have devastating economic and environmental consequences for coastal communities, especially in those areas with low mangrove diversity and high mangrove area or species loss. Several species at high risk of extinction may disappear well before the next decade if existing protective measures are not enforced

Exile Vol. XXXIX No. 1

Title Page by Ellen Gurley \u2793 i Epigraph by Ezra Poind ii Table of Contents iii-iv Remaining a Soldier by Kristin Kruse \u2793 1-2 Vietnam War Memorial by Brooke MacKaye 3 We both ride in back by Chris Macaluso \u2793 4 Artwork by Jamie Oliver \u2794 5 Liberal Dirge #1 by Charis Brummitt \u2796 6-7 Artwork (anonymous) 7 Two ex-lovers and a dirty glass door by Chris Macaluso \u2793 8 The Salt of the Air by Kristen Padden \u2793 9-12 Artwork (anonymous) 13 Artwork by Ellen Gurley \u2793 14 Sun-Child by Jen Rudgers \u2796 15 Crazy Horse by Kevin Nix \u2794 16 The Fall of the Western Field by Rich Croft \u2793 17 In the Closet by Beth Widmaier \u2795 18 Winter Strawberries by Katy Rudder \u2793 19 Still Life (anonymous) 19 For This and Much Beyond This Poem by Matt Wanat \u2795 20-21 Artwork by Peggy Ryan \u2793 22 The Cycle Repeats: Apathy by Ishak Kang \u2793 23 The Judge by Ellen Gurley \u2793 24 Pear Colored by Erin Dempsey \u2793 25-26 4-Square by Trey Dunham \u2794 27 Artwork by Jamie Oliver \u2794 28 Ink & Heroine by Rich Croft \u2793 29 Figments by Craig Bowers \u2793 30-31 Malfi Coast (anonymous) 31 Suzanne (anonymous) 32 Hey Stella by Carey Chistie \u2795 33 Turning Leaves by Erin Lott \u2796 34-35 Reclining Nude (anonymous) 35 Blazon by Matt Wanat \u2795 36-37 Artwork by Holly Aikens \u2793 38 Awake by A. Fair \u2796 39 Dell the Barber by Kevin Nix \u2795 40 Artwork by Holly Aikens \u2793 40 Tree House by Katy Rudder \u2793 41-46 Jailbait by Ellison J. Stind \u2795 47 Mother by Charis Brummitt \u2796 48-49 Artwork by Bess Hammer \u2795 49 Private Origami by Trey Dunham \u2794 50 Among the Tendrils of Sleep by J. Trevett Allen \u2795 51 Poet of the Unforgiven by Carey Christie \u2795 52 Stuntman Steve by Andrew Zobay \u2793 53 sculpture by Lily Streett \u2794 53 Wonderings of an Adopted Son by Andy Heckert \u2793 54-55 Artwork by Holly Aikens \u2793 55 Odd Binge by C. N. Polumbus \u2793 56-57 Artwork by Holly Aikens \u2793 57 Artwork by Peggy Ryan \u2793; untitled by Jennifer Wendell \u2794 (superimposed) 58 Shadows of Pearl by Travis Brady \u2793 59-60 October/Rt. 161 by Annette Gallagher 61 Artwork by Jamie Oliver \u2794 61 The Influx by Craig Bowers \u2793 62 Artwork by Michael Norpell \u2794 63 editorial board 64 Editorial decision is shared equally among the Editorial Board. -64 Cover: Jamie Oliver -64 NOTE: With the exeption of Malfi Coast , all artwork listed as anonymous in the published table of contents appears to be signed by Ellen Gurley. 37th Yea

Investigation of NRXN1 deletions: Clinical and molecular characterization

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P  = 6.08 × 10 −7 ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97220/1/35780_ftp.pd

Sexual Phenotype Differences in zic2 mRNA Abundance in the Preoptic Area of a Protogynous Teleost, Thalassoma bifasciatum

The highly conserved members of the zic family of zinc-finger transcription factors are primarily known for their roles in embryonic signaling pathways and regulation of cellular proliferation and differentiation. This study describes sexual phenotype differences in abundances of zic2 mRNA in the preoptic area of the hypothalamus, a region strongly implicated in sexual behavior and function, in an adult teleost, Thalassoma bifasciatum. The bluehead wrasse (Thalassoma bifasciatum) is a valuable model for studying neuroendocrine processes because it displays two discrete male phenotypes, initial phase (IP) males and territorial, terminal phase (TP) males, and undergoes socially-controlled protogynous sex change. Previously generated microarray-based comparisons suggested that zic2 was upregulated in the brains of terminal phase males relative to initial phase males. To further explore this difference, we cloned a 727 bp sequence for neural zic2 from field-collected animals. Riboprobe-based in situ hybridization was employed to localize zic2 signal in adult bluehead brains and assess the relative abundance of brain zic2 mRNA across sexual phenotypes. We found zic2 mRNA expression was extremely abundant in the granular cells of the cerebellum and widespread in other brain regions including in the thalamus, hypothalamus, habenula, torus semicircularis, torus longitudinalis, medial longitudinal fascicle and telencephalic areas. Quantitative autoradiography and phosphorimaging showed zic2 mRNA hybridization signal in the preoptic area of the hypothalamus was significantly higher in terminal phase males relative to both initial phase males and females, and silver grain analysis confirmed this relationship between phenotypes. No significant difference in abundance was found in zic2 signal across phenotypes in the habenula, a brain region not implicated in the control of sexual behavior, or cerebellum

In vitro models of medulloblastoma: choosing the right tool for the job

The recently-defined four molecular subgroups of medulloblastoma have required updating of our understanding of in vitro models to include molecular classification and risk stratification features from clinical practice. This review seeks to build a more comprehensive picture of the in vitro systems available for modelling medulloblastoma. The subtype classification and molecular characterisation for over 40 medulloblastoma cell-lines has been compiled, making it possible to identify the strengths and weaknesses in current model systems. Less than half (18/44) of established medulloblastoma cell-lines have been subgrouped. The majority of the subgrouped cell-lines (11/18) are Group 3 with MYC-amplification. SHH cell-lines are the next most common (4/18), half of which exhibit TP53 mutation. WNT and Group 4 subgroups, accounting for 50% of patients, remain underrepresented with 1 and 2 cell-lines respectively. In vitro modelling relies not only on incorporating appropriate tumour cells, but also on using systems with the relevant tissue architecture and phenotype as well as normal tissues. Novel ways of improving the clinical relevance of in vitro models are reviewed, focusing on 3D cell culture, extracellular matrix, co-cultures with normal cells and organotypic slices. This paper champions the establishment of a collaborative online-database and linked cell-bank to catalyse preclinical medulloblastoma research