1,201 research outputs found

    Men and women from the STRIDE clinical trial: An assessment of stimulant abstinence symptom severity at residential treatment entry

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    Background and Objectives Gender‐specific factors associated with stimulant abstinence severity were examined in a stimulant abusing or dependent residential treatment sample (N = 302). Method Bivariate statistics tested gender differences in stimulant abstinence symptoms, measured by participant‐reported experiences of early withdrawal. Multivariate linear regression examined gender and other predictors of stimulant abstinence symptom severity. Results Women compared to men reported greater stimulant abstinence symptom severity. Anxiety disorders and individual anxiety‐related abstinence symptoms accounted for this difference. African American race/ethnicity was predictive of lower stimulant abstinence severity. Discussion and Conclusions Women were more sensitive to anxiety‐related stimulant withdrawal symptoms. Scientific Significance Clinics that address anxiety‐related abstinence symptoms, which more commonly occur in women, may improve treatment outcome. (Am J Addict 2015;XX:XX –XX

    Roles of Bcl-3 in the Pathogenesis of Murine Type 1 Diabetes

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    OBJECTIVE: It has long been recognized that autoimmunity is often associated with immunodeficiency. The mechanism underlying this paradox is not well understood. Bcl-3 (B-cell lymphoma 3) is an atypical member of the IκB (inhibitor of the nuclear factor-κB) family that is required for lymphoid organogenesis and germinal center responses. Mice deficient in Bcl-3 are immunodeficient because of the microarchitectural defects of their lymphoid organs. The goal of this study is to define the potential roles of Bcl-3 in type 1 diabetes. <p/>RESEARCH DESIGN AND METHODS: Bcl-3–deficient NOD mice were generated by backcrossing Bcl-3–deficient C57BL/6 mice to NOD mice. Spontaneous and induced type 1 diabetes were studied in these mice by both pathologic and immunologic means. The effect of Bcl-3 on inflammatory gene transcription was evaluated in a promoter reporter assay. <p/>RESULTS: We found that Bcl-3–deficient NOD and C57BL/6 mice were, paradoxically, more susceptible to autoimmune diabetes than wild-type mice. The increase in diabetes susceptibility was caused by Bcl-3 deficiency in hematopoietic cells but not nonhematopoietic cells. Bcl-3 deficiency did not significantly affect anti-islet Th1 or Th2 autoimmune responses, but markedly increased inflammatory chemokine and T helper 17 (Th17)-type cytokine expression. Upon transfection, Bcl-3 significantly inhibited the promoter activities of inflammatory chemokine and cytokine genes. <p/>CONCLUSIONS: These results indicate that in addition to mediating lymphoid organogenesis, Bcl-3 prevents autoimmune diabetes by inhibiting inflammatory chemokine and cytokine gene transcription. Thus, a single Bcl3 gene mutation leads to both autoimmunity and immunodeficiency

    Ultrafast trapping times in ion implanted InP

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    As⁺ and P⁺implantation was performed on semi-insulating (SI) and p-type InP samples for the purpose of creating a material suitable for ultrafast optoelectronic applications. SI InP samples were implanted with a dose of 1×10¹⁶ cm⁻² and p-type InP was implanted with doses between 1×10¹² and 1×10¹⁶ cm⁻². Subsequently, rapid thermal annealing at temperatures between 400 and 700 °C was performed for 30 sec. Hall-effect measurements, double-crystal x-ray diffraction, and time-resolved femtosecond differential reflectivity showed that, for the highest-annealing temperatures, the implanted SI InP samples exhibited high mobility, low resistivity, short response times, and minimal structural damage. Similar measurements on implantedp-type InP showed that the fast response time, high mobility, and good structural recovery could be retained while increasing the resistivity

    Regulation of NF-κB by PML and PML-RARα

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    Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML−/− cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB

    Cerebellar infarction requiring surgical decompression in patient with COVID 19 pathological analysis and brief review

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    © 2020 The Authors Background: This report and literature review describes a case of a COVID-19 patient who suffered a cerebellar stroke requiring neurosurgical decompression. This is the first reported case of a sub-occipital craniectomy with brain biopsy in a COVID-19 patient showing leptomeningeal venous intimal inflammation. Clinical description: The patient is a 48-year-old SARS-COV-2 positive male with multiple comorbidities, who presented with fevers and respiratory symptoms, and imaging consistent with multifocal pneumonia. On day 5 of admission, the patient had sudden change in mental status, increased C-Reactive Protein, ferritin and elevated Interleukin-6 levels. Head CT showed cerebral infarction from vertebral artery occlusion. Given subsequent rapid neurologic decline from cerebellar swelling and mass effect on his brainstem emergent neurosurgical intervention was performed. Brain biopsy found a vein with small organizing thrombus adjacent to focally proliferative intima with focal intimal neutrophils. Conclusion: A young man with COVID-19 and suspected immune dysregulation, complicated by a large cerebrovascular ischemic stroke secondary to vertebral artery thrombosis requiring emergent neurosurgical intervention for decompression with improved neurological outcomes. Brain biopsy was suggestive of inflammation from thrombosed vessel, and neutrophilic infiltration of cerebellar tissue
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