Fecal Microbiota Functional Gene Effects Related to Single-Dose Antibiotic Treatment of Travelers' Diarrhea.

BACKGROUND: Travelers' diarrhea (TD) is common among military personnel deployed to tropical and subtropical regions. It remains unclear how TD and subsequent antibiotic treatment impact the resident microflora within the gut, especially given increased prevalence of antibiotic resistance among enteric pathogens and acquisition of multidrug-resistant organisms. We examined functional properties of the fecal microflora in response to TD, along with subsequent antibiotic treatment. METHODS: Fecal samples from US and UK military service members deployed to Djibouti, Kenya, and Honduras who presented with acute watery diarrhea were collected. A sample was collected at acute presentation to the clinic (day 0, before antibiotics), as well as 7 and/or 21 days following a single dose of antibiotics (azithromycin [500 mg], levofloxacin [500 mg], or rifaximin [1650 mg], all with loperamide). Each stool sample underwent culture and TaqMan reverse transcription polymerase chain reaction analyses for pathogen and antibiotic resistance gene detection. Purified DNA from each sample was analyzed using the HumiChip3.1 functional gene array. RESULTS: In total, 108 day 1 samples, 50 day 7 samples, and 94 day 21 samples were available for analysis from 119 subjects. Geographic location and disease severity were associated with distinct functional compositions of fecal samples. There were no overt functional differences between pre- and postantibiotic treatment samples, nor was there increased acquisition of antibiotic resistance determinants for any of the antibiotic regimens. CONCLUSIONS: These results indicate that single-dose antibiotic regimens may not drastically alter the functional or antibiotic resistance composition of fecal microflora, which should inform clinical practice guidelines and antimicrobial stewardship. CLINICAL TRIALS REGISTRATION NUMBER: NCT01618591.

Gut microbiota and metabolic marker alteration following dietary isoflavone-photoperiod interaction.

Introduction: The interaction between isoflavones and the gut microbiota has been highlighted as a potential regulator of obesity and diabetes. In this study, we examined the interaction between isoflavones and a shortened activity photoperiod on the gut microbiome. Methods: Male mice were exposed to a diet containing no isoflavones (NIF) or a regular diet (RD) containing the usual isoflavones level found in a standard vivarium chow. These groups were further divided into regular (12L:12D) or short active (16L:8D) photoperiod, which mimics seasonal changes observed at high latitudes. White adipose tissue and genes involved in lipid metabolism and adipogenesis processes were analysed. Bacterial genomic DNA was isolated from fecal boli, and 16S ribosomal RNA sequencing was performed. Results: NIF diet increased body weight and adipocyte size when compared to mice on RD. The lack of isoflavones and photoperiod alteration also caused dysregulation of lipoprotein lipase (Lpl), glucose transporter type 4 (Glut-4) and peroxisome proliferator-activated receptor gamma (Pparg) genes. Using 16S ribosomal RNA sequencing, we found that mice fed the NIF diet had a greater proportion of Firmicutes than Bacteroidetes when compared to animals on the RD. These alterations were accompanied by changes in the endocrine profile, with lower thyroid-stimulating hormone levels in the NIF group compared to the RD. Interestingly, the NIF group displayed increased locomotion as compared to the RD group. Conclusion: Together, these data show an interaction between the gut bacterial communities, photoperiod length and isoflavone compounds, which may be essential for understanding and improving metabolic health.

Daily stressors and diurnal cortisol among sexual and gender minority young adults.

OBJECTIVE: Minority stress may contribute to poor health by dysregulating stress response systems, including diurnal cortisol rhythms. However, few studies have examined the association between sexual and gender minority stress and diurnal cortisol in lesbian, gay, bisexual, and transgender (LGBT) individuals. The current investigation tested whether the daily experience of minority stressors is uniquely related to diurnal cortisol above and beyond general stressors. METHOD: One hundred and 21 sexual and gender minority young adults (aged 18-35, 54.5% female) completed initial and daily evening questionnaires for 7 consecutive days to document daily general stressors and LGBT stressors. A randomly selected subset (n = 58) also provided salivary cortisol samples at wake, 45-min postwake, 12-hr postwake, and bedtime. RESULTS: Controlling for covariates (sex assigned at birth, wake time, bedtime, and day of the week) and general stressors, individuals who reported more LGBT stressors across the week displayed elevated cortisol levels at wake, t(491) = 9.68, p = .002 and 45-min postwake, t(492) = 6.41, p = .011, relative to individuals who reported fewer LGBT stressors. In contrast, after controlling for covariates, the frequency of general stressors only predicted cortisol 12 hr postwake, t(785) = 2.02, p = .043. Diurnal cortisol was unrelated to within-person fluctuations in LGBT and general stressors. CONCLUSIONS: Results imply that the experience of everyday minority stressors is uniquely related to diurnal cortisol and may have implications for the mental and physical health of LGBT adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Genetic and Virulence Profiles of Enteroaggregative Escherichia coli (EAEC) Isolated From Deployed Military Personnel (DMP) With Travelers' Diarrhea.

To discern if there was a particular genotype associated with clinical enteroaggregative Escherichia coli (EAEC) strains isolated from deployed military personnel (DMP) with travelers' diarrhea (TD), we characterized a collection of EAEC from DMP deployed to Afghanistan, Djibouti, Kenya, or Honduras. Although we did not identify a specific EAEC genotype associated with TD in DMP, we found that EAEC isolated at the first clinic visit were more likely to encode the dispersin gene aap than EAEC collected at follow-up visits. A majority of the EAEC isolates were typical EAEC that adhered to HEp-2 cells, formed biofilms, and harbored genes for aggregative adherence fimbriae (AAF), AggR, and serine protease autotransporters of Enterobacteriaceae (SPATEs). A separate subset of the EAEC had aggR and genes for SPATEs but encoded a gene highly homologous to that for CS22, a fimbriae more commonly found in enterotoxigenic E. coli. None of these CS22-encoding EAEC formed biofilms in vitro or adhered to HEp-2 cells. Whole genome sequence and single nucleotide polymorphism analyses demonstrated that most of the strains were genetically diverse, but that a few were closely related. Isolation of these related strains occurred within days to more than a year apart, a finding that suggests a persistent source and genomic stability. In an ampicillin-treated mouse model we found that an agg4A+ aar- isolate formed a biofilm in the intestine and caused reduced weight gain in mice, whereas a strain that did not form an in vivo biofilm caused no morbidity. Our diverse strain collection from DMP displays the heterogeneity of EAEC strains isolated from human patients, and our mouse model of infection indicated the genotype agg4A+ aar- and/or capacity to form biofilm in vivo may correlate to disease severity.

Gender differences in innate responses and gene expression profiles in memory CD4 T cells are apparent very early during acute simian immunodeficiency virus infection.

Gender differences in Human immunodeficiency virus (HIV) disease progression and comorbidities have been extensively reported. Using the simian immunodeficiency virus (SIV) infected rhesus macaque model, we show that these differences are apparent very early during the course of infection. Though there were no major changes in the proportions of CD4 T cells or its subsets, central memory CD4 T cells from female macaques were found to differentially regulate a significantly larger number of genes at day 4 post-infection (PI) as compared to males. Pathway analysis revealed divergence of both canonical and biological pathways that persisted at day 10 PI. Changes in gene expression profiles were accompanied by a significant increase in plasma levels of pro-inflammatory mediators such as MCP-1/CCL2, I-TAC/CXCL11, and MIF. Though plasma levels of IFNα did not differ between male and female macaques, the expression levels of IFNα subtype-14, 16, IFNß, and IFNω were significantly upregulated in the lymph nodes of female macaques at day 10 PI as compared to male macaques. Our results suggest that the pathogenic sequelae seen during chronic infection may be shaped by gender differences in immune responses induced very early during the course of HIV infection.

Molecular Cobalt Catalysts for H2 Generation with Redox Activity and Proton Relays in the Second Coordination Sphere.

Two new Co(II) complexes have been synthesized and investigated as catalysts for H2 generation. These catalysts were designed to incorporate redox-active bipyridine components and nitrogen groups, which can participate in electron and proton transfer steps in the catalytic cycle. The two catalysts differ by only one amino group, yielding a completely closed macrocycle and an open "macrocycle" complex. Removing just one nitrogen linker between the Co(II)-binding bipyridine groups has a profound impact on the molecular geometry observed by single crystal analysis. Photocatalysis experiments show that both catalysts are highly active for aqueous proton reduction at moderate pH levels, with the closed macrocycle reaching almost 2 × 104 turnovers of H2 when photodriven by [Ru(2,2'-bipyridine)3]2+ using ascorbate as an electron relay and a phosphine compound as the terminal electron donor. Measurements of the electrocatalytic activity were used to investigate key steps in the mechanism of proton reduction by the molecular catalysts. The formation of a new reversible peak on addition of moderately strong acids in organic solvents suggests that protonation of the macrocycle plays an important role in H2 generation. Onset of the catalytic current occurs near the reduction potential of the bipyridine components, suggesting that catalysis is mediated by electron transfer from the macrocycle to the cobalt center. From these observations, we propose a mechanism for catalytic proton reduction to H2, which involves both intramolecular proton and electron transfer steps from the macrocycle ligand to the cobalt center. The vital role of the second coordination sphere in the catalytic cycle places these relatively simple complexes on the pathway toward molecular catalysts that mimic the valuable features of enzymatic catalysis.

Investigation of a Cluster of Sphingomonas koreensis Infections.

BACKGROUND: Plumbing systems are an infrequent but known reservoir for opportunistic microbial pathogens that can infect hospitalized patients. In 2016, a cluster of clinical sphingomonas infections prompted an investigation. METHODS: We performed whole-genome DNA sequencing on clinical isolates of multidrug-resistant Sphingomonas koreensis identified from 2006 through 2016 at the National Institutes of Health (NIH) Clinical Center. We cultured S. koreensis from the sinks in patient rooms and performed both whole-genome and shotgun metagenomic sequencing to identify a reservoir within the infrastructure of the hospital. These isolates were compared with clinical and environmental S. koreensis isolates obtained from other institutions. RESULTS: The investigation showed that two isolates of S. koreensis obtained from the six patients identified in the 2016 cluster were unrelated, but four isolates shared more than 99.92% genetic similarity and were resistant to multiple antibiotic agents. Retrospective analysis of banked clinical isolates of sphingomonas from the NIH Clinical Center revealed the intermittent recovery of a clonal strain over the past decade. Unique single-nucleotide variants identified in strains of S. koreensis elucidated the existence of a reservoir in the hospital plumbing. Clinical S. koreensis isolates from other facilities were genetically distinct from the NIH isolates. Hospital remediation strategies were guided by results of microbiologic culturing and fine-scale genomic analyses. CONCLUSIONS: This genomic and epidemiologic investigation suggests that S. koreensis is an opportunistic human pathogen that both persisted in the NIH Clinical Center infrastructure across time and space and caused health care-associated infections. (Funded by the NIH Intramural Research Programs.).

Segmental intestinal dilatation associated with ileal gastric heterotopia in a young woman.

Segmental intestinal dilatation (SID) is a rare gastrointestinal disorder characterized by marked bowel dilatation and can result in signs of intestinal obstruction, abdominal pain and gastrointestinal bleeding. SID is seen most commonly in pediatric patients, with most cases being reported in neonates and infants. Definitive treatment is resection of the dilated segment of bowel with primary anastomosis. This article describes a rare case of SID in an adult patient-a 26-year-old female who presented with chronic abdominal pain. The patient experienced complete resolution of symptoms following surgical resection.

Structure and dynamics of Helicobacter pylori nickel-chaperone HypA: an integrated approach using NMR spectroscopy, functional assays and computational tools.

Helicobacter pylori HypA (HpHypA) is a metallochaperone necessary for maturation of [Ni,Fe]-hydrogenase and urease, the enzymes required for colonization and survival of H. pylori in the gastric mucosa. HpHypA contains a structural Zn(II) site and a unique Ni(II) binding site at the N-terminus. X-ray absorption spectra suggested that the Zn(II) coordination depends on pH and on the presence of Ni(II). This study was performed to investigate the structural properties of HpHypA as a function of pH and Ni(II) binding, using NMR spectroscopy combined with DFT and molecular dynamics calculations. The solution structure of apo,Zn-HpHypA, containing Zn(II) but devoid of Ni(II), was determined using 2D, 3D and 4D NMR spectroscopy. The structure suggests that a Ni-binding and a Zn-binding domain, joined through a short linker, could undergo mutual reorientation. This flexibility has no physiological effect on acid viability or urease maturation in H. pylori. Atomistic molecular dynamics simulations suggest that Ni(II) binding is important for the conformational stability of the N-terminal helix. NMR chemical shift perturbation analysis indicates that no structural changes occur in the Zn-binding domain upon addition of Ni(II) in the pH 6.3-7.2 range. The structure of the Ni(II) binding site was probed using 1H NMR spectroscopy experiments tailored to reveal hyperfine-shifted signals around the paramagnetic metal ion. On this basis, two possible models were derived using quantum-mechanical DFT calculations. The results provide a comprehensive picture of the Ni(II) mode to HpHypA, important to rationalize, at the molecular level, the functional interactions of this chaperone with its protein partners.

When Family Matters Most: A Test of the Association Between Sexual Minority Identity Disclosure Context and Diurnal Cortisol in Sexual Minority Young Adults.

OBJECTIVE: Revealing one's sexual identity to others is a complex process marked by a shift in the types of stressors faced by sexual minority young adults. Such stressors influence the secretion of health-relevant hormones, including cortisol, yet how dimensions of disclosure (i.e., the degree and context) influence neuroendocrine functioning remains poorly understood. The current study examined the association between disclosure context (disclosure to family members, friends/co-workers/acquaintances, and members of religious groups) and diurnal cortisol while allowing disclosure to vary in degree (i.e., how much is disclosed). METHODS: One hundred twenty-one sexual minority young adults (aged 18-35 years, 54.5% female, free of major psychiatric/endocrine disorders) completed an initial survey that assessed the degree and context of sexual minority identity disclosure. A randomly selected subset (n = 58) also provided salivary cortisol samples at wake, 45 minutes after wake, 12 hours after wake, and at bedtime for 1 week. RESULTS: Greater total disclosure and greater disclosure to family members were associated with reduced cortisol output, defined as Area Under the Curve relative to ground (AUCg; F(1,230) = 5.95, p = .015, and F(1,231) = 10.90, p = .001, respectively). Disclosure to co-workers, friends, acquaintances, or religious groups was unrelated to cortisol AUCg. All disclosure contexts tested were unrelated to the shape of diurnal cortisol slopes (including the cortisol awakening response). CONCLUSIONS: Disclosure to family members uniquely predicted cortisol AUCg. Therefore, these results suggest that effects of disclosure on diurnal cortisol and its associated health outcomes may occur in the context of familial relationships.

Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance.

The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader range of locations, including housekeeping closets, wastewater from hospital internal pipes, and external manholes. We compared these data with previously collected information from 5 years of patient clinical and surveillance isolates. Whole-genome sequencing and analysis of 108 isolates provided comprehensive characterization of blaKPC/blaNDM-positive isolates, enabling an in-depth genetic comparison. Strikingly, despite a very low prevalence of patient infections with blaKPC-positive organisms, all samples from the intensive care unit pipe wastewater and external manholes contained carbapenemase-producing organisms (CPOs), suggesting a vast, resilient reservoir. We observed a diverse set of species and plasmids, and we noted species and susceptibility profile differences between environmental and patient populations of CPOs. However, there were plasmid backbones common to both populations, highlighting a potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes. Clear associations between patient and environmental isolates were uncommon based on sequence analysis and epidemiology, suggesting reasonable infection control compliance at our institution. Nonetheless, a probable nosocomial transmission of Leclercia sp. from the housekeeping environment to a patient was detected by this extensive surveillance. These data and analyses further our understanding of CPOs in the hospital environment and are broadly relevant to the design of infection control strategies in many infrastructure settings.IMPORTANCE Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections. A 5-year genomic and epidemiological survey was undertaken to study the CPOs in the patient-accessible environment, as well as in the plumbing system removed from the patient. This comprehensive survey revealed a vast, unappreciated reservoir of CPOs in wastewater, which was in contrast to the low positivity rate in both the patient population and the patient-accessible environment. While there were few patient-environmental isolate associations, there were plasmid backbones common to both populations. These results are relevant to all hospitals for which CPO colonization may not yet be defined through extensive surveillance.

Trait Rumination Predicts Elevated Evening Cortisol in Sexual and Gender Minority Young Adults.

Stress may contribute to illness through the impaired recovery or sustained activity of stress-responsive biological systems. Rumination, or mental rehearsal of past stressors, may alter the body's stress-responsive systems by amplifying and prolonging exposure to physiological mediators, such as cortisol. The primary aim of the current investigation was to test the extent to which the tendency to ruminate on stress predicts diminished diurnal cortisol recovery (i.e., elevated evening cortisol) in a sample of sexual and gender minority young adults. Participants included 58 lesbian, gay, bisexual, and transgender young adults (Mage = 25.0, SD = 4.1) who completed an initial online survey that assessed trait rumination and current depressed mood. Participants completed daily evening questionnaires and provided salivary cortisol samples at wake, 45 min post-wake, 12 h post-wake, and at bedtime over seven consecutive days. Trait rumination predicted significantly higher cortisol concentrations at bedtime, but was unrelated to other cortisol indices (e.g., morning cortisol, diurnal slope, total output). The association with trait rumination was not accounted for by daily negative affect, and was largely independent of depressed mood. These results have implications for identifying and treating those who may be at risk for impaired diurnal cortisol recovery and associated negative health outcomes.

Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation.

Intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease. However, a causal role of oral bacteria ectopically colonizing the intestine remains unclear. Using gnotobiotic techniques, we show that strains of Klebsiella spp. isolated from the salivary microbiota are strong inducers of T helper 1 (TH1) cells when they colonize in the gut. These Klebsiella strains are resistant to multiple antibiotics, tend to colonize when the intestinal microbiota is dysbiotic, and elicit a severe gut inflammation in the context of a genetically susceptible host. Our findings suggest that the oral cavity may serve as a reservoir for potential intestinal pathobionts that can exacerbate intestinal disease.

Nickel Ligation of the N-Terminal Amine of HypA Is Required for Urease Maturation in Helicobacter pylori.

The human pathogen Helicobacter pylori requires nickel for colonization of the acidic environment of the stomach. HypA, a Ni metallochaperone that is typically associated with hydrogenase maturation, is also required for urease maturation and acid survival of H. pylori. There are two proposed Ni site structures for HypA; one is a paramagnetic six-coordinate site characterized by X-ray absorption spectroscopy (XAS) in unmodified HypA, while another is a diamagnetic four-coordinate planar site characterized by solution nuclear magnetic resonance in an N-terminally modified HypA construct. To determine the role of the N-terminal amine in Ni binding of HypA, an N-terminal extension variant, L2*-HypA, in which a leucine residue was inserted into the second position of the amino acid sequence in the proposed Ni-binding motif, was characterized in vitro and in vivo. Structural characterization of the Ni site using XAS showed a coordination change from six-coordinate in wild-type HypA (WT-HypA) to five-coordinate pyramidal in L2*-HypA, which was accompanied by the loss of two N/O donor protein ligands and the addition of an exogenous bromide ligand from the buffer. The magnetic properties of the Ni sites in WT-HypA compared to those of the Ni sites in L2*-HypA confirmed that a spin-state change from high to low spin accompanied this change in structure. The L2*-HypA H. pylori strain was shown to be acid sensitive and deficient in urease activity in vivo. In vitro characterization showed that L2*-HypA did not disrupt the HypA-UreE interaction that is essential for urease maturation but was at least 20-fold weaker in Ni binding than WT-HypA. Characterization of the L2*-HypA variant clearly demonstrates that the N-terminal amine of HypA is involved in proper Ni coordination and is necessary for urease activity and acid survival.

Bacterial Etiology and Risk Factors Associated with Cellulitis and Purulent Skin Abscesses in Military Trainees.

Military trainees are at high risk for skin and soft-tissue infections (SSTIs). Although Staphylococcus aureus is associated with purulent SSTI, it is unclear to what degree this pathogen causes nonpurulent cellulitis. To inform effective prevention strategies and to provide novel insights into SSTI pathogenesis, we aimed to determine the etiology of SSTI in this population. We conducted a prospective observational study in US Army Infantry trainees with SSTI (cutaneous abscesses and cellulitis) from July 2012 through December 2014. We used standard microbiology, serology, and high-throughput sequencing to determine the etiology of SSTI. Furthermore, we compared purported risk factors as well as anatomic site colonization for S. aureus. Among 201 SSTI cases evaluated for SSTI risk factors, cellulitis was associated with lower extremity blisters (P = 0.01) and abscess was associated with methicillin-resistant S. aureus (MRSA) colonization (P<0.001). Among the 22 tested cellulitis cases that were part of the microbiome analysis, only 1 leading edge aspirate was culturable (Coagulase-negative Staphylococcus). Microbiome evaluation of aspirate specimens demonstrated that Rhodanobacter terrae was the most abundant species (66.8% average abundance), while abscesses were dominated by S. aureus (92.9% average abundance). Although abscesses and cellulitis share the spectrum of clinical SSTI, the bacterial etiologies as determined by current technology appear distinct. Furthermore, the presence of atypical bacteria within cellulitis aspirates may indicate novel mechanisms of cellulitis pathogenesis. CLINICAL TRIALS REGISTRATION: NCT01105767.

Multi-Body-Site Microbiome and Culture Profiling of Military Trainees Suffering from Skin and Soft Tissue Infections at Fort Benning, Georgia.

Skin and soft tissue infections (SSTIs) are common in the general population, with increased prevalence among military trainees. Previous research has revealed numerous nasal microbial signatures that correlate with SSTI development and Staphylococcus aureus colonization. Thus, we hypothesized that the ecology of the inguinal, oropharynx, and perianal regions may also be altered in response to SSTI and/or S. aureus colonization. We collected body site samples from 46 military trainees with purulent abscess (SSTI group) as well as from 66 asymptomatic controls (non-SSTI group). We also collected abscess cavity samples to assess the microbial composition of these infections. Samples were analyzed by culture, and the microbial communities were characterized by high-throughput sequencing. We found that the nasal, inguinal, and perianal regions were similar in microbial composition and significantly differed from the oropharynx. We also observed differences in Anaerococcus and Streptococcus abundance between the SSTI and non-SSTI groups for the nasal and oropharyngeal regions, respectively. Furthermore, we detected community membership differences between the SSTI and non-SSTI groups for the nasal and inguinal sites. Compared to that of the other regions, the microbial compositions of the nares of S. aureus carriers and noncarriers were dramatically different; we noted an inverse correlation between the presence of Corynebacterium and the presence of Staphylococcus in the nares. This correlation was also observed for the inguinal region. Culture analysis revealed elevated methicillin-resistant S. aureus (MRSA) colonization levels for the SSTI group in the nasal and inguinal body sites. Together, these data suggest significant microbial variability in patients with SSTI as well as between S. aureus carriers and noncarriers. IMPORTANCE While it is evident that nasal colonization with S. aureus increases the likelihood of SSTI, there is a significant lack of information regarding the contribution of extranasal colonization to the overall risk of a subsequent SSTI. Furthermore, the impact of S. aureus colonization on bacterial community composition outside the nasal microbiota is unclear. Thus, this report represents the first investigation that utilized both culture and high-throughput sequencing techniques to analyze microbial dysbiosis at multiple body sites of healthy and diseased/colonized individuals. The results described here may be useful in the design of future methodologies to treat and prevent SSTIs.

Myeloid Cell Nuclear Differentiation Antigen (MNDA) Expression Distinguishes Extramedullary Presentations of Myeloid Leukemia From Blastic Plasmacytoid Dendritic Cell Neoplasm.

Myeloid neoplasms constitute one of the most common malignancies in adults. In most cases these proliferations initially manifest in the blood and marrow; however, extramedullary involvement may precede blood or marrow involvement in a subset of cases, making a definitive diagnosis challenging by morphologic and immunohistochemical assessment alone. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive entity that frequently presents in extramedullary sites and can show morphologic and immunophenotypic overlap with myeloid neoplasms. Given that BPDCN and myeloid neoplasms may both initially present in extramedullary sites and that novel targeted therapies may be developed that exploit the unique molecular signature of BPDCN, new immunophenotypic markers that can reliably separate myeloid neoplasms from BPDCN are desirable. We evaluated the utility of myeloid cell nuclear differentiation antigen (MNDA) expression in a series of extramedullary myeloid leukemias (EMLs) and BPDCN. Forty biopsies containing EML and 19 biopsies containing BPDCN were studied by MNDA immunohistochemistry. The majority of myeloid neoplasms showed nuclear expression of MNDA (65%). In contrast, all cases of BPDCN lacked MNDA expression. These findings show that MNDA is expressed in the majority of EMLs and support the inclusion of MNDA immunohistochemistry in the diagnostic evaluation of blastic hematopoietic infiltrates, particularly when the differential diagnosis is between myeloid leukemia and BPDCN.

Intervention effects on safety compliance and citizenship behaviors: Evidence from the Work, Family, and Health Study.

We tested the effects of a work-family intervention on employee reports of safety compliance and organizational citizenship behaviors in 30 health care facilities using a group-randomized trial. Based on conservation of resources theory and the work-home resources model, we hypothesized that implementing a work-family intervention aimed at increasing contextual resources via supervisor support for work and family, and employee control over work time, would lead to improved personal resources and increased employee performance on the job in the form of self-reported safety compliance and organizational citizenship behaviors. Multilevel analyses used survey data from 1,524 employees at baseline and at 6-month and 12-month postintervention follow-ups. Significant intervention effects were observed for safety compliance at the 6-month, and organizational citizenship behaviors at the 12-month, follow-ups. More specifically, results demonstrate that the intervention protected against declines in employee self-reported safety compliance and organizational citizenship behaviors compared with employees in the control facilities. The hypothesized mediators of perceptions of family-supportive supervisor behaviors, control over work time, and work-family conflict (work-to-family conflict, family-to-work conflict) were not significantly improved by the intervention. However, baseline perceptions of family-supportive supervisor behaviors, control over work time, and work-family climate were significant moderators of the intervention effect on the self-reported safety compliance and organizational citizenship behavior outcomes.

Recurrent Methicillin-Resistant Staphylococcus aureus Cutaneous Abscesses and Selection of Reduced Chlorhexidine Susceptibility during Chlorhexidine Use.

We describe the selection of reduced chlorhexidine susceptibility during chlorhexidine use in a patient with two episodes of cutaneous USA300 methicillin-resistant Staphylococcus aureus abscess. The second clinical isolate harbors a novel plasmid that encodes the QacA efflux pump. Greater use of chlorhexidine for disease prevention warrants surveillance for resistance.

Cytogenetic Variation of B-Lymphoblastic Leukemia With Intrachromosomal Amplification of Chromosome 21 (iAMP21): A Multi-Institutional Series Review.

OBJECTIVES: B-lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21) is a relatively uncommon manifestation of acute leukemia and limited predominantly to the pediatric population. Case-specific information regarding flow cytometric, morphologic, and laboratory findings of this subtype of leukemia is currently lacking. METHODS: We searched the databases of three large institutions for lymphoblastic leukemia with iAMP21 from 2005 through 2012 and analyzed the clinicopathologic features. RESULTS: We identified 17 cases with five or more RUNX1 signals on interphase nuclei, 14 of which were consistent with the Children's Oncology Group (COG) definition for iAMP21­namely, the presence of three or more RUNX1 signals on one marker chromosome. These cases showed a statistically significant lower peripheral WBC count and older age at diagnosis compared with all pediatric cases of B-ALL. We also identified three cases with increased RUNX1 signals scattered on multiple marker chromosomes that did not meet the COG definition of iAMP21 but showed similar 21q instability and older age at presentation. CONCLUSIONS: Our findings not only demonstrate that B-ALL with iAMP21 is truly a distinct clinicopathologic entity but also suggest that a subset of cases of B-ALL with iAMP21 can show variable cytogenetic features.