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Background The mammalian gut harbors very complex and diverse microbiota that play an important role in intestinal homeostasis and host health. Exposure to radiation results in dysbiosis of the gut microbiota leading to detrimental pathophysiological changes to the host. To alleviate the effects of irradiation, several candidate countermeasures are under investigation. BIO 300, containing synthetic genistein formulated as an amorphous solid dispersion or as an aqueous suspension of nanoparticles, is a promising candidate under advanced development. The aim of this study was to investigate the effects of BIO 300 on the gut microbiome and metabolome of mice exposed to 60Co gamma-radiation. The gut microbiota and metabolome of control and drug-treated mice exposed to radiation was characterized by bacterial 16S rRNA amplicon sequencing and untargeted metabolomics. Results We found that irradiation altered the Firmicutes/Bacteroidetes ratio and significantly decreased the relative abundance of Lactobacillus, both in BIO 300-treated and control mice; however, the ratio returned to near normal levels in BIO 300-treated mice by day 14 post-irradiation. Concomitantly, we also observed corrective shifts in metabolic pathways that were perturbed after irradiation. Conclusions Overall, the data presented show that radiation exposure led to a relative depletion of commensals like Lactobacillus leading to an inflammatory metabolic phenotype while the majority of the drug-treated mice showed alleviation of this condition primarily by restoration of normal gut microbiota. These results indicate that the radioprotective effects of BIO 300, at least in part, may involve correction of the host-microbiome metabolic axis.

[...]there is great potential for attitudes and decision-making processes regarding working while sick to change, hopefully for the better. [...]what once was a largely private and personal decision based on a somewhat limited set of antecedents (see Miraglia & Johns, 2016) is now multifaceted, emotionally charged, and perhaps (hopefully?) more morally derived and other-focused than before. Research suggests that emphasizing harm to others, as compared with emphasizing harm to oneself, increases engagement in personal safety behaviors (e.g., Grant & Hoffman, 2011). [...]we suggest additional investigation as to whether considering other stakeholders in decision making can be leveraged for changing presenteeism beliefs and behaviors. An opportunity for lasting positive change At present, the many ways in which the COVID-19 pandemic has disrupted the world through premature loss of life, declining health, income and job insecurity, social tension, and more are clear.

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) 2020 APA, all rights reserved).

This study examines the process through which family interference with work (FIW) negatively relates to safety performance in two unique samples from high-risk industries. Using a sample from the construction industry, Study 1 finds that FIW is related to employees' workplace cognitive failures, which in turn, were a significant predictor of safety-related behaviors. Using a sample from a utility company, Study 2 replicates these results and demonstrates that psychological strain further explains the complex relationship between FIW and safety. Furthermore, in Study 2, the mediation pathways linking FIW with safety behaviors were moderated by employees' commitment to safety. The idea that family life can predict safety in the workplace through interference and distraction is important to the collective effort to protect worker health and critical to effective intervention design.

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.)

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 th...

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.

Cover caption: The cover image is based on the Original Article Gut Microbiota and Metabolic Marker Alteration Following Dietary Isoflavone‐Photoperiod Interaction by Tao‐yiao Wu et al.,https://doi.org/10.1002/edm2.232. [Image: see text]

In this paper we present a fully CMOS-compatible fabrication process for GaN-on-Si monolithic microwave integrated circuits (MMICs) on 200-mm-diameter wafers. This process also enables wafer-level 3D integration of GaN MMICs with Si CMOS circuits to enhance performance and functionality while reducing the size, weight, power, as well as the cost. We demonstrate our progress towards full 3D integration, including a discussion on GaN HEMT fabrication and bonding with a Si CMOS wafer. With the use of an InA1N barrier layer we show a GaN-on-Si HEMT output power of 4.5 W/mm and PAE of 53% at 10 GHz.

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., Isoflavones are known to shift the metabolic state. In this study, we found that this effect is accentuated during short active photoperiods. Removal of isoflavones shifted the microbiome composition to one that resembles that observed in obese models, accompanied by increased adipocyte size and the expression of markers of metabolic dysfunction

A substantial literature has established that obesity is negatively associated with wages, particularly among females. However, prior research has found limited evidence for the factors hypothesized to underlie the obesity wage penalty. We add to the literature using data from IT workers at a U.S. Fortune 500 firm that provides us with direct measures of employee income and BMI, and health measures that are unavailable in national-level datasets. Our estimates indicate that the wage-obesity penalty among females only occurs among obese mothers, and is not attributable to differences in health or human capital that may be caused by having children. Published: Online November 2018.

The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset—accessible through the Beat AML data viewer (Vizome)—that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML. Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.

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.

The relationship between mindfulness (i.e., monitoring present experiences with acceptance) and diurnal cortisol has been the subject of growing interest. However, no studies have examined how distinct mindfulness subcomponents of awareness and acceptance may independently or interactively predict diurnal cortisol rhythms. As such, the present project aimed to test the relationship between self-reported mindful awareness and acceptance, and diurnal cortisol in a sample of sexual minority young adults (SMYA). As part of a larger project examining the health of SMYA, 121 SMYA, free of major psychiatric and endocrine disorders, completed an initial survey and daily evening questionnaires for 1 week. A randomly selected subset (n = 58) also provided salivary cortisol samples at wake, 45-min post-wake, 12-h post-wake, and at bedtime over 7 days. Dispositional mindfulness was measured using the Five Facet Mindfulness Inventory-Short Form at the beginning of the study. Greater trait mindful awareness was associated with a smaller cortisol awakening response. In contrast, greater trait mindful acceptance was associated with a more robust cortisol awakening response and a sharper decrease in the evening. Distinguishing between mindful awareness and acceptance may be especially important for predicting diurnal cortisol rhythms and associated outcomes. These findings provide critical insight to researchers evaluating physiological outcomes associated with mindfulness.

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.

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, IFNβ, 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.

Members of the genera Hydrogenovibrio, Thiomicrospira, and Thiomicrorhabdus fix carbon at hydrothermal vents, coastal sediments, hypersaline lakes, and other sulfidic habitats. The genome sequences of these ubiquitous and prolific chemolithoautotrophs suggest a surprising diversity of mechanisms for the uptake and fixation of dissolved inorganic carbon (DIC); these mechanisms are verified here. Carboxysomes are apparent in the transmission electron micrographs of most of these organisms but are lacking in Thiomicrorhabdus sp. strain Milos-T2 and Thiomicrorhabdus arctica, and the inability of Thiomicrorhabdus sp. strain Milos-T2 to grow under low-DIC conditions is consistent with the absence of carboxysome loci in its genome. For the remaining organisms, genes encoding potential DIC transporters from four evolutionarily distinct families (Tcr_0853 and Tcr_0854, Chr, SbtA, and SulP) are located downstream of carboxysome loci. Transporter genes collocated with carboxysome loci, as well as some homologs located elsewhere on the chromosomes, had elevated transcript levels under low-DIC conditions, as assayed by reverse transcription-quantitative PCR (qRT-PCR). DIC uptake was measureable via silicone oil centrifugation when a representative of each of the four types of transporter was expressed in Escherichia coli The expression of these genes in the carbonic anhydrase-deficient E. coli strain EDCM636 enabled it to grow under low-DIC conditions, a result consistent with DIC transport by these proteins. The results from this study expand the range of DIC transporters within the SbtA and SulP transporter families, verify DIC uptake by transporters encoded by Tcr_0853 and Tcr_0854 and their homologs, and introduce DIC as a potential substrate for transporters from the Chr family.IMPORTANCE Autotrophic organisms take up and fix DIC, introducing carbon into the biological portion of the global carbon cycle. The mechanisms for DIC uptake and fixation by autotrophic Bacteria and Archaea are likely to be diverse but have been well characterized only for "Cyanobacteria" Based on genome sequences, members of the genera Hydrogenovibrio, Thiomicrospira, and Thiomicrorhabdus have a variety of mechanisms for DIC uptake and fixation. We verified that most of these organisms are capable of growing under low-DIC conditions, when they upregulate carboxysome loci and transporter genes collocated with these loci on their chromosomes. When these genes, which fall into four evolutionarily independent families of transporters, are expressed in E. coli, DIC transport is detected. This expansion in known DIC transporters across four families, from organisms from a variety of environments, provides insight into the ecophysiology of autotrophs, as well as a toolkit for engineering microorganisms for carbon-neutral biochemistries of industrial importance.

Two new Co(II) complexes have been synthesized and investigated as catalysts for H

International audience; 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.

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.

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.

On average, well over half of the population of people with disabilities (PWD) is unemployed. This is unsustainable, particularly considering the increase in the average age of the global populatio...

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).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.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).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.

This work presents a study of circuit component design in a new GaN-on-Si process being developed by the MIT Lincoln Laboratory. The process uses a thick silicon substrate with no through-vias with a multi-layer stack-up. Examples of components required for MMIC design include lines of various impedances, shorted and open stubs, tees, meander lines, and capacitors. Because the fabrication process requires the use of ungrounded CPW lines, underpasses are necessary to connect ground planes and a study of 50-Ohm lines with several underpass spacings is performed. The large range of dimensions and dielectric constants presents a challenge for full-wave simulations, and a comparison between Ansys HFSS and Sonnet Software is presented for a variety of passive circuit components implemented in the GaN-on-Si MMIC stack-up.

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.

The incidence of skin and soft tissue infections (SSTIs) has increased dramatically over the past decade, resulting in significant morbidity in millions of otherwise healthy individuals worldwide. Certain groups, like military personnel, are at increased risk for SSTI development. Although nasal colonization with Staphylococcus aureus is an important risk factor for the development of SSTIs, it is not clear why some colonized individuals develop disease while others do not. Recent studies have revealed the importance of microbial diversity in human health. Therefore, we hypothesized that the nasal microbiome may provide valuable insight into SSTI development. To examine this hypothesis, we obtained anterior-naris samples from military trainees with cutaneous abscesses and from asymptomatic (non-SSTI) participants. We also obtained samples from within abscess cavities. Specimens were analyzed by culture, and the microbial community within each sample was characterized using a 16S sequencing-based approach. We collected specimens from 46 non-SSTI participants and from 40 participants with abscesses. We observed a significantly higher abundance of Proteobacteria in the anterior nares in non-SSTI participants ( P < 0.0001) than in participants with abscesses. Additionally, we noted a significant inverse correlation between Corynebacterium spp. and S. aureus ( P = 0.0001). The sensitivity of standard microbiological culture for abscesses was 71.4%. These data expand our knowledge of the complexity of the nasal and abscess microbiomes and potentially pave the way for novel therapeutic and prophylactic countermeasures against SSTI.

Helicobacter pylori requires urease activity in order to survive in the acid environment of the human stomach. Urease is regulated in part by nickelation, a process that requires the HypA protein, which is a putative nickel metallochaperone that is generally associated with hydrogenase maturation. However, in H. pylori, HypA plays a dual role. In addition to an N-terminal nickel binding site, HypA proteins also contain a structural zinc site that is coordinated by two rigorously conserved CXXC sequences, which in H. pylori are flanked by His residues. These structural Zn sites are known to be dynamic, converting from Zn(Cys)4 centers at pH 7.2 to Zn(Cys)2(His)2 centers at pH 6.3 in the presence of Ni(ii) ions. In this study, mutant strains of H. pylori that express zinc site variants of the HypA protein are used to show that the structural changes in the zinc site are important for the acid viability of the bacterium, and that a reduction in acid viability in these variants can be traced in large measure to deficient urease activity. This in turn leads to a model that connects the Zn(Cys)4 coordination to urease maturation.

Gas phase spectral measurements for CdSe/ZnS core/shell nanocrystal quantum dots (QDs) before and after heating with both infrared (CO2) and visible lasers are reported. As-trapped QDs are spectrally similar to the same QDs in solution; however their photoluminescence (PL) intensities are very low, at least partly due to low absorption cross sections. After heating, the PL intensities brighten by factors ranging from ∼4 to 1800 depending on the QD size and pump laser wavelength. The emission spectra no longer resemble solution spectra and are similar, regardless of the QD diameter. Emission extends from the pump laser wavelength into the near-IR, with strong emission features above the band gap energy, between 645 and 775 nm, and in the near-infrared. Emission spectra from brightened QD ensembles, single QD aggregates, and single QD monomers are similar, showing that even single QDs support PL from a wide variety of states. The heating and cooling processes for QDs in this environment are analyzed, providing limits on the magnitudes of the absorption cross sections before and after thermal brightening. A model, based on absorption bleaching by extra electrons in the conduction band, appears to account for the changes in absorption and emission behavior induced by charging and heating.

Objectives: We retrospectively tested the prognostic and diagnostic significance of CD271+ mesenchymal stromal cell (MSC) density in cytopenic patients who underwent bone marrow biopsy to evaluate for myelodysplastic syndromes (MDS). Methods: CD271+ MSC density was quantitated by automated image analysis of tissue microarray cores in 125 cytopenic patients: 40 lower grade MDS (

Gut reasons to brush your teeth Some gut conditions, such as inflammatory bowel disease (IBD), ulcerative colitis, and Crohn's disease (CD), are associated with imbalances in the gut microbe community. The causes of these intractable diseases have been difficult to discern. Atarashi et al. took samples from the mouths of IBD and CD patients and inoculated the extracted bacteria into germ-free mice (see the Perspective by Cao). Some of the inoculated mice showed strong proliferation of T helper 1 cells associated with the establishment of oral Klebsiella species in the colon. Klebsiella can be resistant to multiple antibiotics and are able to replace normal colon microbes after antibiotic therapy. Now we know that they probably originate from the mouth and could potentially contribute to bowel disease. Science , this issue p. 359 ; see also p. 308

Eosinophilia in the peripheral blood is classified as primary (clonal) hematologic neoplasms or secondary (nonclonal) disorders, associated with hematologic or nonhematologic disorders. This review focuses on the categories of hematolymphoid neoplasms recognized by the 2008 World Health Organization Classification of Tumours and Haematopoietic and Lymphoid Tissues that are characteristically associated with eosinophilia. We provide a systematic approach to the diagnosis of these neoplastic proliferations via morphologic, immunophenotypic, and molecular-based methodologies, and provide the clinical settings in which these hematolymphoid neoplasms occur. We discuss recommendations that eosinophilia working groups have published addressing some of the limitations of the current classification scheme.

[Aims]: CD30 expression by bone marrow (BM) mast cells (MC) has been reported recently in systemic mastocytosis (SM) patients. The aim of this study was to investigate the potential diagnostic and prognostic value of CD30 expression in SM as assessed by multiparameter flow cytometry. [Methods and results]: A total of 163 consecutive BM samples corresponding to 142 SM patients and 21 non-mastocytosis cases were studied. CD30 was positive in most SM patients (80%), but in only one non-mastocytosis case (4.8%). When combined with CD25, CD30 contributed to an improved accuracy over that of CD25 alone (98% versus 93%) mainly because most (eight of nine) of the well-differentiated SM (WDSM), who lacked CD25, were CD30+. Similar levels of expression of CD30 were observed among all different subgroups of SM except mast cell leukaemia; among indolent SM (ISM) patients, no significant association was observed between the levels of CD30 expression and other clinical and biological features of the disease. [Conclusions]: The increased expression of CD30 associated with absence of CD25 contributes to the diagnosis of WDSM and its distinction from other subtypes of SM. By contrast, CD30 expression did not contribute either to prognostic stratification of ISM or to the differential diagnosis between ISM and aggressive SM cases., This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS) PI11/02399, PS09/00032 and RETICs RD09/0076/00133, RD09/0076/00074 and RD12/0036/0048 (FEDER) from the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain; Fundacion Sociosanitaria de Castilla-La Mancha (2010/008 y G-2010/C-002); Fundación Espanola de Mastocitosis (FEM 2010); and by a grant from Fundaçao para a Ciência e Tecnologia (FCT) of Portugal (SFRH/BD/22972/2005).

Objectives: To assess a large series of patients with acute myeloid leukemia (AML) with t(8;21) for both IGH@ and IGK@ B-cell gene rearrangements and for expression of PAX5, OCT2, and Bob.1 by immunohistochemistry and expression of CD19, CD79a, CD20, and CD22 by flow cytometry immunophenotyping. Methods: A total of 48 cases of AML with t(8;21)(q22;q22) were evaluated by immunohistochemistry and/or heavy chain and light chain immunoglobulin rearrangement studies where paraffin-embedded and/or fresh frozen material was available for study; previously performed flow cytometry studies were also reviewed in available cases. Results: Our study yielded 1 of 19 cases of AML with t(8;21) with an IGH@ gene rearrangement; blasts were associated with weak PAX5 expression. In addition, expression of antigens CD79a by flow cytometry and OCT2 by immunohistochemistry were highly associated with PAX5 expression, and CD19 was expressed in most cases assessed. Conclusions: Although B-cell antigen and B-cell transcription factor expression is seen in the majority of AMLs with t(8;21)(q22;q22) and correlates with PAX5 expression, immunoglobulin gene rearrangements are an uncommon event in this group of leukemias.

T-cell lymphomas represent a heterogeneous group of neoplasms that encompass considerable clinical, morphologic, and immunophenotypic variation. The diagnosis of T-cell lymphoma is challenging because of its relative rarity, the lack of an immunophenotypic marker of clonality, and significant morphologic overlap with infectious/inflammatory processes and neoplasms, including Hodgkin and other non-Hodgkin lymphomas, and even mesenchymal or epithelial lesions. In the current World Health Organization classification of hematopoietic tumors, all except 1 subtype (ie, T-lymphoblastic lymphoma) are recognized as mature neoplasms derived from postthymic T cells. In addition to T-lymphoblastic lymphoma, this review will focus on nodal and extranodal T-cell lymphomas and exclude T-cell lymphomas presenting primarily in the skin. Extranodal natural-killer-cell/T-cell lymphoma, nasal type, will also be discussed because the derivation of this lymphoma from natural killer and natural killer-like T cells shows morphologic and immunophenotypic features that overlap with other T-cell lymphomas. In this review, we discuss the salient clinicopathologic, immunophenotypic, and genetic features, as well as our approaches to the diagnosis of lymphoblastic, nodal, and extranodal T-cell lymphomas.

The present study tested a process model through which the strain-based (job control and role ambiguity) and time-based (work hours) job demands of employed mothers relate to child health via child modeling of mother's physical activity. Support was found for a model of these relationships using dyadic mother-child data (N = 359) from a large, multi-wave nationwide data set and job demands data from the Occupational Information Network (O*Net). Theoretical and practical implications, as well as future research directions, are also discussed.