97 research outputs found

    Stigma and attitudes toward patients with psychiatric illness among postgraduate Indian physicians

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    BACKGROUND: Due to paucity of psychiatrists in India, psychiatric patients often present to other doctors. We aimed to study nonpsychiatric residents\u27 attitude and stigma toward psychiatric patients. METHODS: A total of 57 postgraduate trainees participated in a cross-sectional study in a tertiary hospital in New Delhi. Attitudes to psychiatric patients were assessed using the attitude to mental illness questionnaire (AMIQ) and the perceived stigma questionnaire. This was correlated with sociodemographic information. RESULTS: Over 70% residents accepted mentally ill patients as friends and felt they were equally employable. However, AMIQ demonstrated a negative attitude towards patients with schizophrenia. Perceived competence in dealing with psychiatric patients was associated with adequate undergraduate exposure (Chi-square = 7.270, CONCLUSIONS: While the questionnaires revealed some prejudice toward psychiatric patients with schizophrenia, the postgraduate trainees who felt competent to deal with the mentally ill had the most positive attitudes toward them

    The Neutrophil:The Underdog That Packs a Punch in the Fight against Cancer

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    The advent of immunotherapy has had a major impact on the outcome and overall survival in many types of cancer. Current immunotherapeutic strategies typically aim to (re)activate anticancer T cell immunity, although the targeting of macrophage-mediated anticancer innate immunity has also emerged in recent years. Neutrophils, although comprising approximate to 60% of all white blood cells in the circulation, are still largely overlooked in this respect. Nevertheless, neutrophils have evident anticancer activity and can induce phagocytosis, trogocytosis, as well as the direct cytotoxic elimination of cancer cells. Furthermore, therapeutic tumor-targeting monoclonal antibodies trigger anticancer immune responses through all innate Fc-receptor expressing cells, including neutrophils. Indeed, the depletion of neutrophils strongly reduced the efficacy of monoclonal antibody treatment and increased tumor progression in various preclinical studies. In addition, the infusion of neutrophils in murine cancer models reduced tumor progression. However, evidence on the anticancer effects of neutrophils is fragmentary and mostly obtained in in vitro assays or murine models with reports on anticancer neutrophil activity in humans lagging behind. In this review, we aim to give an overview of the available knowledge of anticancer activity by neutrophils. Furthermore, we will describe strategies being explored for the therapeutic activation of anticancer neutrophil activity

    High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles

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    Nanoparticles may limit off-tumor/on-target ubiquitous activation of signaling by protein-based drugs. However, many challenges still exist in the design of a nanoparticle for protein delivery. In this study, conditions to establish vaterite nanoparticles as a pH-sensitive drug delivery system (DDS) for encapsulated protein drugs are comprehensively evaluated. Low coprecipitation pH of vaterite and protein prevents protein denaturation and yields high loading efficiency. Unprotected vaterite recrystallizes in aqueous solutions within 3 h to calcite and releases the loaded protein completely, but surface-modified particles with carboxyl groups containing polymers prove stable for more than 5 months. Notably, modification of vaterite with sulfonated polymers increases the loading of cationic proteins by a multiple. A system is developed for vaterite exposure to (pH) conditions under body-like-flow rates, with the dissolution of vaterite and simultaneous release of active proteins at tumor microenvironmental pH reaching up to 80% and only 20% at physiological pH within 2 h. Importantly, the immunomodulatory protein tumor necrosis factor preserves its native structure and fully retains functional activity in vitro after release from the particles. In conclusion, the studies described here provide a framework for the development of vaterite-based DDS as a carrier for bioactive protein-based therapeutics

    Bronchoscopic Intervention May be Associated with Better Outcomes in Mechanically Ventilated Coronavirus Disease-19 Patients: A Case Series

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    BACKGROUND: The emergence of a new strain of coronavirus infection, the coronavirus infection disease 2019 (COVID-19), has been a pandemic burden across the globe. Severe COVID-19, particularly in patients with acute respiratory distress syndrome (ARDS), is associated with increased risk of admission to intensive care unit (ICU), mechanical ventilation, and mortality. Bronchoscopy has been widely employed as an adjunctive therapy in mechanically ventilated patients. However, the use of bronchoscopy in patients with COVID-19 has been strictly limited due to aerosol transmission. CASE REPORT: We reported 3 COVID-19 Cases presented to the hospital with ARDS. All of the patients were immediately intubated to improve oxygenation. During admission, the patients produced immense airway secretions that might have resulted in partial airway obstruction. A conventional tracheal suctioning did not help to promote clinical improvement. We decided to perform bronchoscopy with controlled suctioning by following a very tight protocol to prevent aerosol formation. A significant clinical and respiratory improvement was observed in all patients following bronchoscopy. Three of them were transferred to regular ward, however, one patient died during hospitalization. CONCLUSION: Bronchoscopic procedures may provide significant therapeutic benefits in severe COVID-19 patients. However, it should be kept in mind that this procedure should only be performed with a rigorous protocol to reduce the risk of aerosol generation and subsequent viral transmission

    Evidence That the P\u3csub\u3ei\u3c/sub\u3e Release Event Is the Rate-Limiting Step in the Nitrogenase Catalytic Cycle

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    Nitrogenase reduction of dinitrogen (N2) to ammonia (NH3) involves a sequence of events that occur upon the transient association of the reduced Fe protein containing two ATP molecules with the MoFe protein that includes electron transfer, ATP hydrolysis, Pi release, and dissociation of the oxidized, ADP-containing Fe protein from the reduced MoFe protein. Numerous kinetic studies using the nonphysiological electron donor dithionite have suggested that the rate-limiting step in this reaction cycle is the dissociation of the Fe protein from the MoFe protein. Here, we have established the rate constants for each of the key steps in the catalytic cycle using the physiological reductant flavodoxin protein in its hydroquinone state. The findings indicate that with this reductant, the rate-limiting step in the reaction cycle is not protein–protein dissociation or reduction of the oxidized Fe protein, but rather events associated with the Pi release step. Further, it is demonstrated that (i) Fe protein transfers only one electron to MoFe protein in each Fe protein cycle coupled with hydrolysis of two ATP molecules, (ii) the oxidized Fe protein is not reduced when bound to MoFe protein, and (iii) the Fe protein interacts with flavodoxin using the same binding interface that is used with the MoFe protein. These findings allow a revision of the rate-limiting step in the nitrogenase Fe protein cycle

    CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma

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    CD24 and its ligand Siglec-10 were described as an innate immune checkpoint in carcinoma. Here, we investigated this axis in B-cell lymphoma by assessing CD24 expression and evaluating pro-phagocytic effects of CD24 antibody treatment in comparison to hallmark immune checkpoint CD47. In mantle cell lymphoma (MCL) and follicular lymphoma patients, high mRNA expression of CD24 correlated with poor overall survival, whereas CD47 expression did not. Conversely, CD24 expression did not correlate with survival in diffuse large B-cell lymphoma (DLBCL), whereas CD47 did. CD24 was also highly expressed on MCL cell lines, where treatment with CD24 antibody clones SN3 or ML5 potently induced phagocytosis, with SN3 yielding >90% removal of MCL cells and triggering phagocytosis of primary patient-derived MCL cells by autologous macrophages. Treatment with CD24 mAb was superior to CD47 mAb in MCL and was comparable in magnitude to the effect observed in carcinoma lines. Reversely, CD24 mAb treatment was less effective than CD47 mAb treatment in DLBCL. Finally, phagocytic activity of clone SN3 appeared at least partly independent of antibody-dependent cellular phagocytosis (ADCP), suggesting CD24/Siglec-10 checkpoint activity, whereas clone ML5 solely induced ADCP. In conclusion, CD24 is an immunotherapeutic target of potential clinical relevance for MCL, but not DLBCL

    Community hospitals and their services in the NHS: identifying transferable learning from international developments – scoping review, systematic review, country reports and case studies

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    Background The notion of a community hospital in England is evolving from the traditional model of a local hospital staffed by general practitioners and nurses and serving mainly rural populations. Along with the diversification of models, there is a renewed policy interest in community hospitals and their potential to deliver integrated care. However, there is a need to better understand the role of different models of community hospitals within the wider health economy and an opportunity to learn from experiences of other countries to inform this potential. Objectives This study sought to (1) define the nature and scope of service provision models that fit under the umbrella term ‘community hospital’ in the UK and other high-income countries, (2) analyse evidence of their effectiveness and efficiency, (3) explore the wider role and impact of community engagement in community hospitals, (4) understand how models in other countries operate and asses their role within the wider health-care system, and (5) identify the potential for community hospitals to perform an integrative role in the delivery of health and social care. Methods A multimethod study including a scoping review of community hospital models, a linked systematic review of their effectiveness and efficiency, an analysis of experiences in Australia, Finland, Italy, Norway and Scotland, and case studies of four community hospitals in Finland, Italy and Scotland. Results The evidence reviews found that community hospitals provide a diverse range of services, spanning primary, secondary and long-term care in geographical and health system contexts. They can offer an effective and efficient alternative to acute hospitals. Patient experience was frequently reported to be better at community hospitals, and the cost-effectiveness of some models was found to be similar to that of general hospitals, although evidence was limited. Evidence from other countries showed that community hospitals provide a wide spectrum of health services that lie on a continuum between serving a ‘geographic purpose’ and having a specific population focus, mainly older people. Structures continue to evolve as countries embark on major reforms to integrate health and social care. Case studies highlighted that it is important to consider local and national contexts when looking at how to transfer models across settings, how to overcome barriers to integration beyond location and how the community should be best represented. Limitations The use of a restricted definition may have excluded some relevant community hospital models, and the small number of countries and case studies included for comparison may limit the transferability of findings for England. Although this research provides detailed insights into community hospitals in five countries, it was not in its scope to include the perspective of patients in any depth. Conclusions At a time when emphasis is being placed on integrated and community-based care, community hospitals have the potential to assume a more strategic role in health-care delivery locally, providing care closer to people’s homes. There is a need for more research into the effectiveness and cost-effectiveness of community hospitals, the role of the community and optimal staff profile(s). Funding The National Institute for Health Research Health Services and Delivery Research programme

    Training of child and adolescent psychiatry fellows in autism and intellectual disability

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    Patients with autism spectrum disorders and intellectual disability can be clinically complex and often have limited access to psychiatric care. Because little is known about post-graduate clinical education in autism spectrum disorder and intellectual disability, we surveyed training directors of child and adolescent psychiatry fellowship programs. On average, child and adolescent psychiatry directors reported lectures of 3 and 4 h per year in autism spectrum disorder and intellectual disability, respectively. Training directors commonly reported that trainees see 1-5 patients with autism spectrum disorder or intellectual disability per year for outpatient pharmacological management and inpatient treatment. Overall, 43% of directors endorsed the need for additional resources for training in autism spectrum disorder and intellectual disability, which, coupled with low didactic and clinical exposure, suggests that current training is inadequate
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