1,506 research outputs found

    Debunking Misconceptions

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    Students will have spent much of the semester learning about the history of race in American culture from its beginnings up until 1877. This not only includes the history of slavery, but also the racialization of indigenous peoples and various groups of immigrants (including those today deemed “white”). Students will also have studied key concepts and theories central to racial studies, such as proto-racism, racial formation, racial justice, biological racism, etc. We encourage them to interrogate the concept of race as natural and to consider how race is ideological and how it evolves over time. We also explore how we behave, practice, and enact our lives according to these ideologies and consequently experience race as something that is real. Through this foundational historical and ideological context, they will have a vantage point to reflect back on how their notions about race have evolved throughout the semester.https://scholarworks.sjsu.edu/inclusion-initiative-prompts/1006/thumbnail.jp

    Cognitive behavioral therapy for the management of multiple sclerosis–related pain: a randomized clinical trial

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    BACKGROUND: Pain is a common and often debilitating symptom among persons with multiple sclerosis (PwMS). Besides interfering with daily functioning, pain in MS is associated with higher levels of depression and anxiety. While cognitive-behavioral therapy (CBT) for pain has been found to be an effective treatment in other populations, there has been a dearth of research in PwMS. METHODS: PwMS with at least moderate pain severity (N = 20) were randomly assigned to one of two groups: CBT plus standard care (CBT/SC) or MS-related education plus standard care (ED/SC), each of which met for 12 sessions. Changes in pain severity, pain interference, and depressive symptom severity from baseline to the 15 week follow-up were assessed using a 2×2 factorial design. Participants also rated their satisfaction with their treatment and accomplishment of personally meaningful behavioral goals. RESULTS: Both treatment groups rated their treatment satisfaction as very high and their behavioral goals as largely met, although only the CBT/SC group's mean goal accomplishment ratings represented significant improvement. While there were no significant differences between groups post-treatment on the three primary outcomes, there was an overall improvement over time for pain severity, pain interference, and depressive symptom severity. CONCLUSIONS: CBT or education-based programs may be helpful adjunctive treatments for PwMS experiencing pain.Accepted manuscrip

    A Systematic Analysis of Two-Component Systems of Streptomyces spp.

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    Found in all domains of life, two-component systems (TCSs) are signal transduction pathways which are canonically composed of a membrane bound sensor kinase (SK) and a cognate response regulator (RR). Upon stimulation, the SK relays the signal to the RR through transfer of a phosphate group to a conserved aspartate residue. The active RR~P is then able to modulate gene expression in response to the initial stimulus. This output could be the regulation of metabolite production, development or movement for example. Streptomyces species encode a high number of TCSs which reflects the multitude of environmental challenges they must face. Streptomyces species are prolific producers of bioactive natural products (NPs) and account for over half of the clinically used antibiotics. Many TCSs have been shown to regulate antibiotic biosynthesis including the global regulators MtrAB and AfsQ1/Q2. The newly emerging model organism S. venezuelae possesses 59 TCSs and a predicted 30 NP biosynthetic gene clusters. In this work, a library of TCS operon deletion mutants were generated through PCR targeting and CRISPR/Cas9 gene editing. High throughput screening of this library as well as a more targeted approach through analysis of potential regulons has been utilised in an effort to characterise these mutants. In this study, through analysis of adjacent genes, a TCS was identified to regulate tunicamycin resistance (TunRS; Sven15_3170/71). Another TCS which mediates antibiotic resistance is VanRS, in response to vancomycin. Vancomycin is a glycopeptide antibiotic widely used in clinics to treat infections caused by Gram-positive bacteria such as Staphylococcus aureus and Clostridium difficile, for example. With the emergence and spread of vancomycin resistance, it is important to understand not just the mechanism of reistance but also the mechanism of recognition. This is with the aim to develop a means of sequestering recognition and resistance. It is currently unclear whether vancomycin binds directly to the SK (VanS) or first binding and forming a complex with another cell component. Here, work has been presented on the purification of the membrane protein VanS with the aim of elucidating the mechanism of vancomycin and VanS interaction. The study of TCSs shows us how bacteria link their external surroundings with adaptive responses. The study of TCSs allows us to better understand not just how bacteria perceive their surroundings but could be used as a means to activate biosynthetic gene clusters of desirable products such as bioactives. With many TCSs in the genus Streptomyces uncharacterised, TCSs were rewired in an effort to activate antibiotic production through the RR AfsQ1 via the non-cognate SK VanS, which is involved in vancomycin resistance. The in vitro and in vivo analyses carried out in this investigation to test the effects of these chimeras, have produced results which are inconclusive in determining whether the use of vancomycin is able to activate antibiotic production through an AfsQ1-dependent pathway

    The effect of continuous liver normothermic machine perfusion on the severity of histological bile duct injury

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    Static Cold Storage (SCS) injures the bile duct, while the effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study of the COPE trial on liver NMP, we investigated the impact of preservation type on histological bile duct injury score (BDIS). Transplants with at least one bile duct biopsy, either at end of preservation or 1 h post-reperfusion, were considered. BDIS was determined by assessing peribiliary glands injury, stromal and mural loss, haemorrhage, and thrombosis. A bivariate linear model compared BDIS (estimate, CI) between groups. Sixty-five transplants and 85 biopsies were analysed. Twenty-three grafts were preserved with SCS and 42 with NMP, with comparable baseline characteristics except for a shorter cold ischemic time in NMP. The BDIS increased over time regardless of preservation type (p = 0.04). The BDIS estimate was higher in NMP [8.02 (7.40–8.65)] than in SCS [5.39 (4.52–6.26), p < 0.0001] regardless of time. One patient in each group developed ischemic cholangiopathy, with a BDIS of 6 for the NMP-preserved liver. In six other NMP grafts, BDIS ranged 7–12 without development of ischemic cholangiopathy. In conclusion, BDIS increases over time, and the higher BDIS in NMP did not increase ischemic cholangiopathy. Thus, BDIS may overestimate this risk after liver NMP

    Cancer patient preferences for communication of prognosis in the metastatic setting

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    PURPOSE: To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. PATIENTS AND METHODS: One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. RESULTS: More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P = .047) and average survival (P = .049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P = .03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P = .02). CONCLUSION: Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.<br /

    Diversification of DNA-Binding Specificity by Permissive and Specificity-Switching Mutations in the ParB/Noc Protein Family

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    Specific interactions between proteins and DNA are essential to many biological processes. Yet, it remains unclear how the diversification in DNA-binding specificity was brought about, and the mutational paths that led to changes in specificity are unknown. Using a pair of evolutionarily related DNA-binding proteins, each with a different DNA preference (ParB [Partitioning Protein B] and Noc [Nucleoid Occlusion Factor], which both play roles in bacterial chromosome maintenance), we show that specificity is encoded by a set of four residues at the protein-DNA interface. Combining X-ray crystallography and deep mutational scanning of the interface, we suggest that permissive mutations must be introduced before specificity-switching mutations to reprogram specificity and that mutational paths to new specificity do not necessarily involve dual-specificity intermediates. Overall, our results provide insight into the possible evolutionary history of ParB and Noc and, in a broader context, might be useful for understanding the evolution of other classes of DNA-binding proteins

    Defensive responses to stressful life events associated with cancer diagnosis

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    Objectives: Stressful life events (SLEs) are common in patients who developed both physical and psychological syndromes. Research shown the role of psychological defense mechanisms in cancer progression and survival probability. The present study analyzed recent SLEs and defense mechanisms as characteristic of cancer patients and tested their role as potential predisposing factors to cancer development. Methods: This cross-sectional study enrolled 145 participants: 48 recently diagnosed cancer patients (CP), 43 recently diagnosed benign tumor patients (BT), and 54 healthy subjects (HC). Non-blinded raters assessed participants’ defense mechanisms using the Defense Mechanisms Rating Scales Q-sort version (DMRS-Q). Groups were compared on the presence of SLEs and on the maturity of defensive functioning. Significant associations between SLE and defense mechanisms as related to cancer diagnosis were explored. Results: Higher overall defensive functioning was associated with good physical conditions. Recent SLEs, higher use of neurotic defenses and lower use of obsessional defenses characterized cancer patients. CP showed higher use of suppression, repression, dissociation, rationalization and passive aggression and lower use of affiliation, sublimation, undoing, and devaluation of self-image as compared to controls. Hierarchical regression analysis showed that recent SLEs and defense mechanisms of suppression, repression, dissociation, displacement and omnipotence were associated with cancer diagnosis. Discussion: Recent SLEs and repressive defensive functioning characterized the CP’s defensive response to stress. Despite the relevance of present findings, this study shows several limitations. Prospective and longitudinal studies are needed to confirm these results and to investigate the potential role played by SLEs and defense mechanisms in cancer development
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