Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. METHODS: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. RESULTS: We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13–0.40) than controls (0.12; IQR, 0.09–0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90). CONCLUSIONS: High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. CLINICALTRIALS.GOV IDENTIFIER: NCT01056185

Beauty surveillance: the digital self-monitoring cultures of neoliberalism

This paper argues that ‘beauty apps’ are transforming the arena of appearance politics and foregrounds a theoretical architecture for critically understanding them. Informed by a feminist-Foucaultian framework, it argues that beauty apps offer a technology of gender which brings together digital self-monitoring and postfeminist modalities of subjecthood to produce an hitherto unprecedented regulatory gaze upon women that is marked by the intensification, extensification and psychologization of surveillance. The paper is divided into four sections. First it introduces the literature on digital self-tracking. Secondly it sets out our understanding of neoliberalism and postfeminism. Thirdly it looks at beauty and surveillance, before offering, in the final section, a typology of appearance apps. This is followed by a discussion of the modes of address/authority deployed in these apps – especially what we call ‘surveillant sisterhood’ - and the kinds of entrepreneurial subjectivity they constitute. The paper seeks to make a contribution to feminist surveillance studies and argues that much more detailed research is needed to critically examine beauty apps

Hypersensitivity Pneumonitis-like Granulomatous Lung Disease with Nontuberculous Mycobacteria from Exposure to Hot Water Aerosols

OBJECTIVE: Human activities associated with aerosol-generating hot water sources are increasingly popular. Recently, a hypersensitivity pneumonitis (HP)-like granulomatous lung disease, with non-tuberculous mycobacteria from exposure to hot water aerosols from hot tubs/spas, showers, and indoor swimming pools, has been described in immunocompetent individuals (also called “hot tub lung”). Our objective in this study was to examine four additional cases of hot tub lung and compare these cases with others reported in the English print literature on this disease. DATA SOURCES AND EXTRACTION: We retrospectively reviewed all cases (n = 4) of presumptively diagnosed hot tub lung in immunocompetent individuals at the various physician practices in Springfield, Illinois, during 2001–2005. In addition, we searched MEDLINE for cases of hot tub lung described in the literature. DATA SYNTHESIS: We summarized the clinical presentation and investigations of four presumptive cases and reviewed previously reported cases of hot tub lung. CONCLUSIONS: There is a debate in the literature whether hot tub lung is an HP or a direct infection of the lung by nontuberculous mycobacteria. Primary prevention of this disease relies on ventilation and good use practices. Secondary prevention of this disease requires education of both the general public and clinicians to allow for the early diagnosis of this disease

Gingival Fibroblasts Display Reduced Adhesion and Spreading on Extracellular Matrix: A Possible Basis for Scarless Tissue Repair?

Unlike skin, oral gingiva do not scar in response to injury. The basis of this difference is likely to be revealed by comparing the responses of dermal and gingival fibroblasts to fibrogenic stimuli. Previously, we showed that, compared to dermal fibroblasts, gingival fibroblasts are less responsive to the potent pro-fibrotic cytokine TGFβ, due to a reduced production of endothelin-1 (ET-1). In this report, we show that, compared to dermal fibroblasts, human gingival fibroblasts show reduced expression of pro-adhesive mRNAs and proteins including integrins α2 and α4 and focal adhesion kinase (FAK). Consistent with these observations, gingival fibroblasts are less able to adhere to and spread on both fibronectin and type I collagen. Moreover, the enhanced production of ET-1 mRNA and protein in dermal fibroblasts is reduced by the FAK/src inhibitor PP2. Given our previous observations suggesting that fibrotic fibroblasts display elevated adhesive properties, our data suggest that scarring potential may be based, at least in part, on differences in adhesive properties among fibroblasts resident in connective tissue. Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury

Impact of a silver layer on the membrane of tap water filters on the microbiological quality of filtered water

<p>Abstract</p> <p>Background</p> <p>Bacteria in the hospital's drinking water system represent a risk for the acquisition of a nosocomial infection in the severely immunocompromised host. Terminal tap water filters may be used to prevent nosocomial Legionnaires' disease. We present data from water samples using an improved kind of tap water filters.</p> <p>Methods</p> <p>In a blinded study on an intermediate care unit of the thoracic surgery department, a modified type of the Germlyser water filter (Aqua-Free Membrane Technology) with a newly-introduced silver layer on the filtration membrane was compared to its preceding type without such a layer on 15 water outlets. We determined growth of <it>Legionella</it>, other pathogenic bacteria, and the total heterotrophic plate count in unfiltered water and filtered water samples after filter usage intervals of 1 through 4 weeks.</p> <p>Results</p> <p>A total of 299 water samples were tested. Twenty-nine of the 60 unfiltered water samples contained <it>Legionella </it>of various serogroups (baseline value). In contrast, all samples filtered by the original water filter and all but one of the water samples filtered by the modified filter type remained <it>Legionella</it>-free. No other pathogenic bacteria were detected in any filtered sample. The total plate count in water samples increased during use of both kinds of filters over time. However, for the first 7 days of use, there were significantly fewer water samples containing >100 CFU per mL when using the new filter device compared with the older filters or taps with no filter. No advantage was seen thereafter.</p> <p>Conclusion</p> <p>The use of this type of terminal water filter is an appropriate method to protect immunocompromised patients from water-borne pathogens such as <it>Legionella</it>.</p

Flanker performance in female college students with ADHD: a diffusion model analysis

Attention-deficit hyperactivity disorder (ADHD) is characterized by poor adaptation to environmental demands, which leads to various everyday life problems. The present study had four aims: (1) to compare performance in a flanker task in female college students with and without ADHD (N = 39) in a classical analyses of reaction time and error rate and studying the underlying processes using a diffusion model, (2) to compare the amount of focused attention, (3) to explore the adaptation of focused attention, and (4) to relate adaptation to psychological functioning. The study followed a 2-between (group: ADHD vs. control) × 2-within (flanker conflict: incongruent vs. congruent) × 2-within (conflict frequency: 20 vs. 80 %) design. Compared to a control group, the ADHD group displayed prolonged response times accompanied by fewer errors in a flanker task. Results from the diffusion model analyses revealed that the members of the ADHD group showed deficits in non-decisional processes (i.e., higher non-decision time) and leaned more toward accuracy than participants without ADHD (i.e., setting higher boundaries). The ADHD group showed a more focused attention and less adaptation to the task conditions which is related to psychological functioning. Deficient non-decisional processes and poor adaptation are in line with theories of ADHD and presumably typical for the ADHD population, although this has not been shown using a diffusion model. However, we assume that the cautious strategy of trading speed of for accuracy is specific to the subgroup of female college students with ADHD and might be interpreted as a compensation mechanism

Early reduction in painful physical symptoms is associated with improvements in long-term depression outcomes in patients treated with duloxetine

<p>Abstract</p> <p>Background</p> <p>To investigate the association of the change of painful physical symptoms (PPS) after 4 weeks, with the 6-month treatment outcomes of depressive symptoms in patients treated with duloxetine in clinical practice.</p> <p>Methods</p> <p>Multicenter, prospective, 6-month, non-interventional study in adult outpatients with a depressive episode and starting treatment with duloxetine. Depression severity was assessed by the clinician (Inventory for Depressive Symptomatology [IDS-C]) and patient (Kurz-Skala Stimmung/Aktivierung [KUSTA]). Somatic symptoms and PPS were assessed using the patient-rated Somatic Symptom Inventory (SSI) and visual analog scales (VAS) for pain items. Association of change in PPS with outcomes of depressive symptoms was analyzed based on mean KUSTA scores (mean of items mood, activity, tension/relaxation, sleep) and achievement of a 50% reduction in the total IDS-C score after 6 months using linear and logistic regression models, respectively.</p> <p>Results</p> <p>Of the 4,517 patients enrolled (mean age: 52.2 years, 71.8% female), 3,320 patients (73.5%) completed the study. 80% of the patients had moderate to severe overall pain (VAS > 30 mm) at baseline. A 50% VAS overall pain reduction after 4 weeks was associated with a 13.32 points higher mean KUSTA score after 6 months, and a 50% pain reduction after 2 weeks with a 6.33 points improvement. No unexpected safety signals were detected in this naturalistic study.</p> <p>Conclusion</p> <p>Pain reduction after 2 and 4 weeks can be used to estimate outcomes of long-term treatment with duloxetine. PPS associated with depression have a potential role in predicting remission of depressive symptoms in clinical practice.</p

Crystal Structure of the Minimalist Max-E47 Protein Chimera

Max-E47 is a protein chimera generated from the fusion of the DNA-binding basic region of Max and the dimerization region of E47, both members of the basic region/helix-loop-helix (bHLH) superfamily of transcription factors. Like native Max, Max-E47 binds with high affinity and specificity to the E-box site, 5′-CACGTG, both in vivo and in vitro. We have determined the crystal structure of Max-E47 at 1.7 Å resolution, and found that it associates to form a well-structured dimer even in the absence of its cognate DNA. Analytical ultracentrifugation confirms that Max-E47 is dimeric even at low micromolar concentrations, indicating that the Max-E47 dimer is stable in the absence of DNA. Circular dichroism analysis demonstrates that both non-specific DNA and the E-box site induce similar levels of helical secondary structure in Max-E47. These results suggest that Max-E47 may bind to the E-box following the two-step mechanism proposed for other bHLH proteins. In this mechanism, a rapid step where protein binds to DNA without sequence specificity is followed by a slow step where specific protein:DNA interactions are fine-tuned, leading to sequence-specific recognition. Collectively, these results show that the designed Max-E47 protein chimera behaves both structurally and functionally like its native counterparts