Outpatient Mental Health Service Utilization for Depression and Anxiety Post-Hurricane

Increased depression and anxiety diagnoses are a result of the lack of use or underuse of outpatient mental health services, specifically among African Americans, youths, and the homeless, and this is a current issue in New Orleans, Louisiana post-Hurricane Katrina. Funding constraints due to the termination of the Louisiana Spirit Program contributed to deficits in terms of outpatient mental health facilities in New Orleans. The purpose of this quantitative study was to examine the association between the continuum and utilization of outpatient mental health services for African Americans, youth, and the homeless for those diagnosed with depression and anxiety. Andersen’s behavioral model of healthcare use and Atkinson’s sociocognitive theory were used to identify determinants of healthcare service use among people diagnosed with depression and anxiety. The quantitative study of 1043 cases, utilizing a correlational research design, analyzed data from the Data Center and the Hurricane Katrina Community Advisory Group using cross tabulations with chi-square and multiple logistic regression. The data analysis found statistically significant associations between outpatient mental health services and age and anxiety and race, specifically non-hispanic blacks. Associations were not found between anxiety and homelessness, age, and outpatient mental health services. Additionally, associations were not found between outpatient mental health services and, race and homelessness. The study contributes to positive social change by validating Andersen’s behavioral model for health care use and Atkinson’s socio-cognitive theory as a means for health care administrators to allocate funding for outpatient mental health facilities in New Orleans

A study of the ultrastructure of Fragile-X-related proteins

Fragile-X-related proteins form a family implicated in RNA metabolism. Their sequence is composed of conserved N-terminal and central regions which contain Tudor and KH domains and of a divergent C-terminus with motifs rich in arginine and glycine residues. The most widely studied member of the family is probably FMRP (fragile X mental retardation protein), since absence or mutation of this protein in humans causes fragile X syndrome, the most common cause of inherited mental retardation. Understanding the structural properties of FMRP is essential for correlating it with its functions. The structures of isolated domains of FMRP have been reported, but nothing is yet known with regard to the spatial arrangement of the different modules, partly because of difficulties in producing both the full-length protein and its multidomain fragments in quantities, purities and monodispersity amenable for structural studies. In the present study, we describe how we have produced overlapping recombinant fragments of human FMRP and its paralogues which encompass the evolutionary conserved region. We have studied their behaviour in solution by complementary biochemical and biophysical techniques, identified the regions which promote self-association and determined their overall three-dimensional shape. The present study paves the way to further studies and rationalizes the existing knowledge on the self-association properties of these proteins

Exploring gender and fear retrospectively:stories of women’s fear during the ‘Yorkshire Ripper’ murders

The murder of 13 women in the North of England between 1975 and 1979 by Peter Sutcliffe who became known as the Yorkshire Ripper can be viewed as a significant criminal event due to the level of fear generated and the impact on local communities more generally. Drawing upon oral history interviews carried out with individuals living in Leeds at the time of the murders, this article explores women’s accounts of their fears from the time. This offers the opportunity to explore the gender/fear nexus from the unique perspective of a clearly defined object of fear situated within a specific spatial and historical setting. Findings revealed a range of anticipated fear-related emotions and practices which confirm popular ‘high-fear’ motifs; however, narrative analysis of interviews also highlighted more nuanced articulations of resistance and fearlessness based upon class, place and biographies of violence, as well as the way in which women drew upon fear/fearlessness in their overall construction of self. It is argued that using narrative approaches is a valuable means of uncovering the complexity of fear of crime and more specifically provides renewed insight onto women’s fear

Down-Regulation of the Interferon Signaling Pathway in T Lymphocytes from Patients with Metastatic Melanoma

BACKGROUND: Dysfunction of the immune system has been documented in many types of cancers. The precise nature and molecular basis of immune dysfunction in the cancer state are not well defined. METHODS AND FINDINGS: To gain insights into the molecular mechanisms of immune dysfunction in cancer, gene expression profiles of pure sorted peripheral blood lymphocytes from 12 patients with melanoma were compared to 12 healthy controls. Of 25 significantly altered genes in T cells and B cells from melanoma patients, 17 are interferon (IFN)-stimulated genes. These microarray findings were further confirmed by quantitative PCR and functional responses to IFNs. The median percentage of lymphocytes that phosphorylate STAT1 in response to interferon-α was significantly reduced (Δ = 16.8%; 95% confidence interval, 0.98% to 33.35%) in melanoma patients (n = 9) compared to healthy controls (n = 9) in Phosflow analysis. The Phosflow results also identified two subgroups of patients with melanoma: IFN-responsive (33%) and low-IFN-response (66%). The defect in IFN signaling in the melanoma patient group as a whole was partially overcome at the level of expression of IFN-stimulated genes by prolonged stimulation with the high concentration of IFN-α that is achievable only in IFN therapy used in melanoma. The lowest responders to IFN-α in the Phosflow assay also showed the lowest gene expression in response to IFN-α. Finally, T cells from low-IFN-response patients exhibited functional abnormalities, including decreased expression of activation markers CD69, CD25, and CD71; T(H)1 cytokines interleukin-2, IFN-γ, and tumor necrosis factor α, and reduced survival following stimulation with anti-CD3/CD28 antibodies compared to controls. CONCLUSIONS: Defects in interferon signaling represent novel, dominant mechanisms of immune dysfunction in cancer. These findings may be used to design therapies to counteract immune dysfunction in melanoma and to improve cancer immunotherapy

Fish assemblage stability over fifty years in the Lake Pontchartrain Estuary; comparisons among habitats using Canonical Correspondence Analysis

We assessed fish assemblage stability over the last half century in Lake Pontchartrain, an environmentally degraded oligohaline estuary in southeastern Louisiana. Because assemblage instability over time has been consistently associated with severe habitat degradation, we attempted to determine whether fish assemblages in demersal, nearshore, and pelagic habitats exhibited change that was unrelated to natural fluctuations in environmental variables (e.g., assemblage changes between wet and dry periods). Collection data from three gear types (trawl, beach seine, and gill nets) and monthly environmental data (salinity, temperature, and Secchi depth) were compared for four collecting periods: 1954 (dry period), 1978 (wet period), 1996–1998 (wet period), and 1998–2000 (dry period). Canonical correspondence analysis (CCA) revealed that although the three environmental variables were significantly associated with the distribution and abundance patterns of fish assemblages in all habitats (with the exception of Secchi depth for pelagic samples), most fish assemblage change occurred among sampling periods (i.e., along a temporal gradient unrelated to changing environmental variables). Assemblage instability was the most pronounced for fishes collected by trawls from demersal habitats. A marked lack of cyclicity in the trawl data CCA diagram indicated a shift away from a baseline demersal assemblage of 50 yr ago. Centroid positions for the five most collected species indicated that three benthic fishes, Atlantic croaker (Micropogonias undulatus), spot (Leiostomus xanthurus), and hardhead catfish (Arius felis), were more dominant inWe assessed fish assemblage stability over the last half century in Lake Pontchartrain, an environmentally degraded oligohaline estuary in southeastern Louisiana. Because assemblage instability over time has been consistently associated with severe habitat degradation, we attempted to determine whether fish assemblages in demersal, nearshore, and pelagic habitats exhibited change that was unrelated to natural fluctuations in environmental variables (e.g., assemblage changes between wet and dry periods). Collection data from three gear types (trawl, beach seine, and gill nets) and monthly environmental data (salinity, temperature, and Secchi depth) were compared for four collecting periods: 1954 (dry period), 1978 (wet period), 1996–1998 (wet period), and 1998–2000 (dry period). Canonical correspondence analysis (CCA) revealed that although the three environmental variables were significantly associated with the distribution and abundance patterns of fish assemblages in all habitats (with the exception of Secchi depth for pelagic samples), most fish assemblage change occurred among sampling periods (i.e., along a temporal gradient unrelated to changing environmental variables). Assemblage instability was the most pronounced for fishes collected by trawls from demersal habitats. A marked lack of cyclicity in the trawl data CCA diagram indicated a shift away from a baseline demersal assemblage of 50 yr ago. Centroid positions for the five most collected species indicated that three benthic fishes, Atlantic croaker (Micropogonias undulatus), spot (Leiostomus xanthurus), and hardhead catfish (Arius felis), were more dominant in past demersal assemblages (1954 and 1978). A different situation was shown for planktivorous species collected by trawls with bay anchovy (Anchoa mitchilli) becoming more dominant in recent assemblages and Gulf enhaden (Brevoortia patronus) remaining equally represented in assemblages over time. Changes in fish assemblages from nearshore (beach seine) and pelagic (gill net) habitats were more closely related to environmental fluctuations, though the CCA for beach seine data also indicated a decrease in the dominance of M. undulatus and an increase in the proportion of A. mitchilli over time. The reduced assemblage role of benthic fishes and the marked assemblage change indicated by trawl data suggest that over the last half century demersal habitats in Lake Pontchartrain have been impacted more by multiple anthropogenic stressors than nearshore or pelagic habitats. past demersal assemblages (1954 and 1978). A different situation was shown for planktivorous species collected by trawls with bay anchovy (Anchoa mitchilli) becoming more dominant in recent assemblages and Gulf menhaden (Brevoortia patronus) remaining equally represented in assemblages over time. Changes in fish assemblages from nearshore (beach seine) and pelagic (gill net) habitats were more closely related to environmental fluctuations, though the CCA for beach seine data also indicated a decrease in the dominance of M. undulatus and an increase in the proportion of A. mitchilli over time. The reduced assemblage role of benthic fishes and the marked assemblage change indicated by trawl data suggest that over the last half century demersal habitats in Lake Pontchartrain have been impacted more by multiple anthropogenic stressors than nearshore or pelagic habitats

Human TRIM Gene Expression in Response to Interferons

Tripartite motif (TRIM) proteins constitute a family of proteins that share a conserved tripartite architecture. The recent discovery of the anti-HIV activity of TRIM5α in primate cells has stimulated much interest in the potential role of TRIM proteins in antiviral activities and innate immunity.To test if TRIM genes are up-regulated during antiviral immune responses, we performed a systematic analysis of TRIM gene expression in human primary lymphocytes and monocyte-derived macrophages in response to interferons (IFNs, type I and II) or following FcγR-mediated activation of macrophages. We found that 27 of the 72 human TRIM genes are sensitive to IFN. Our analysis identifies 9 additional TRIM genes that are up-regulated by IFNs, among which only 3 have previously been found to display an antiviral activity. Also, we found 2 TRIM proteins, TRIM9 and 54, to be specifically up-regulated in FcγR-activated macrophages.Our results present the first comprehensive TRIM gene expression analysis in primary human immune cells, and suggest the involvement of additional TRIM proteins in regulating host antiviral activities

Mutations in Protein-Binding Hot-Spots on the Hub Protein Smad3 Differentially Affect Its Protein Interactions and Smad3-Regulated Gene Expression

Hub proteins are connected through binding interactions to many other proteins. Smad3, a mediator of signal transduction induced by transforming growth factor beta (TGF-β), serves as a hub protein for over 50 protein-protein interactions. Different cellular responses mediated by Smad3 are the product of cell-type and context dependent Smad3-nucleated protein complexes acting in concert. Our hypothesis is that perturbation of this spectrum of protein complexes by mutation of single protein-binding hot-spots on Smad3 will have distinct consequences on Smad3-mediated responses.We mutated 28 amino acids on the surface of the Smad3 MH2 domain and identified 22 Smad3 variants with reduced binding to subsets of 17 Smad3-binding proteins including Smad4, SARA, Ski, Smurf2 and SIP1. Mutations defective in binding to Smad4, e.g., D408H, or defective in nucleocytoplasmic shuttling, e.g., W406A, were compromised in modulating the expression levels of a Smad3-dependent reporter gene or six endogenous Smad3-responsive genes: Mmp9, IL11, Tnfaip6, Fermt1, Olfm2 and Wnt11. However, the Smad3 mutants Y226A, Y297A, W326A, K341A, and E267A had distinct differences on TGF-β signaling. For example, K341A and Y226A both reduced the Smad3-mediated activation of the reporter gene by ∼50% but K341A only reduced the TGF-β inducibilty of Olfm2 in contrast to Y226A which reduced the TGF-β inducibility of all six endogenous genes as severely as the W406A mutation. E267A had increased protein binding but reduced TGF-β inducibility because it caused higher basal levels of expression. Y297A had increased TGF-β inducibility because it caused lower Smad3-induced basal levels of gene expression.Mutations in protein binding hot-spots on Smad3 reduced the binding to different subsets of interacting proteins and caused a range of quantitative changes in the expression of genes induced by Smad3. This approach should be useful for unraveling which Smad3 protein complexes are critical for specific biological responses

Remote control of gene function by local translation

The subcellular position of a protein is a key determinant of its function. Mounting evidence indicates that RNA localization, where specific mRNAs are transported subcellularly and subsequently translated in response to localized signals, is an evolutionarily conserved mechanism to control protein localization. On-site synthesis confers novel signaling properties to a protein and helps to maintain local proteome homeostasis. Local translation plays particularly important roles in distal neuronal compartments, and dysregulated RNA localization and translation cause defects in neuronal wiring and survival. Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo