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BACKGROUND AND AIMS: This systematic review sought to identify, explain and interpret the prominent or recurring themes relating to the barriers and facilitators of reporting and recording of self-harm in young people across different settings, such as the healthcare setting, schools and the criminal justice setting. METHODS: A search strategy was developed to ensure all relevant literature around the reporting and recording of self-harm in young people was obtained. Literature searches were conducted in six databases and a grey literature search of policy documents and relevant material was also conducted. Due to the range of available literature, both quantitative and qualitative methodologies were considered for inclusion. RESULTS: Following the completion of the literature searches and sifting, nineteen papers were eligible for inclusion. Facilitators to reporting self-harm across the different settings were found to be recognising self-harm behaviours, using passive screening, training and experience, positive communication, and safe, private information sharing. Barriers to reporting self-harm included confidentiality concerns, negative perceptions of young people, communication difficulties, stigma, staff lacking knowledge around self-harm, and a lack of time, money and resources. Facilitators to recording self-harm across the different settings included being open to discussing what is recorded, services working together and co-ordinated help. Barriers to recording self-harm were mainly around stigma, the information being recorded and the ability of staff being able to do so, and their length of professional experience. CONCLUSION: Following the review of the current evidence, it was apparent that there was still progress to be made to improve the reporting and recording of self-harm in young people, across the different settings. Future work should concentrate on better understanding the facilitators, whilst aiming to ameliorate the barriers.
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Comportamento Autodestrutivo , Humanos , Adolescente , Comportamento Autodestrutivo/diagnóstico , Estigma Social , Instituições AcadêmicasRESUMO
OBJECTIVE: In-hospital stroke cases occur during hospitalization for another diagnosis and reflect a clinically distinct cohort from community-onset stroke. The objective was to validate the diagnostic accuracy of in-hospital stroke identification in stroke audit data at a large teaching hospital. METHODS: A retrospective clinical validation of in-hospital stroke diagnoses from two linked data sources was completed for a 2-year period from January 1st 2020 to December 31st 2021. The linked data sources include the Hospital Inpatient Enquiry system which assigns coded stroke diagnoses at discharge and/or the local stroke audit coordinators who work clinically in stroke teams and input additional specific clinical data. Diagnostic sensitivity, specificity and the level of agreement using an unweighted Cohen's Kappa were calculated. RESULTS: There were 597 strokes admitted during the 2-year period. The median age was 72 years and 55% occurred in males. In total, 88 cases of in-hospital stroke were clinically validated yielding an in-hospital stroke rate of 15%. The clinical audit coordinator identified in-hospital stroke with higher sensitivity (86%; 95% CI 77%-93%) whereas the coding process was more specific at 96% (95% CI 85% to 99%). Levels of agreement with the clinically validated gold standard sample were moderate for the audit coordinator and coding process with κ = 0.57 and K = 0.42 respectively. When both data sources were combined the level of agreement was substantial (κ = 0.65; p < .000). CONCLUSIONS: Clinical validation studies are required to reinforce data quality within stroke registers. Combining clinical and administrative data sources improves diagnostic accuracy for in-hospital stroke identification.
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Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Hospitais , Hospitalização , Alta do PacienteRESUMO
OBJECTIVE: To report the diagnostic features and clinical outcome of horses with digital flexor tendon sheath (DFTS) synoviocoeles treated tenoscopically under ultrasonographic guidance. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned horses (n = 10). METHODS: Medical records were searched for horses with lameness localized to the region of the DFTS and clinical evidence of a fluid-filled mass (synoviocoele) associated with the DFTS. Diagnostic imaging and surgical findings, together with long-term outcome, were reported. RESULTS: Lameness and synoviocoeles were unilateral (5 forelimbs, 5 hindlimbs; 3 lateral and 2 medial in both) and located proximal to the palmar/plantar annular ligament. Synoviocoeles had a firm consistency and focal pain with inability to deflate on non-weight-bearing examination. Intrathecal DFTS anesthesia was positive in 7/8 horses in which it was performed, with the remainder localized to the region of the synoviocoele using perineural and/or intralesional anesthesia. Communication between the DFTS and synoviocoele was suspected ultrasonographically in all cases and confirmed on contrast tenography (6/6). Tenoscopic fenestration of the communication between the DFTS and synoviocoele under ultrasonographic guidance, with treatment of concurrent intrathecal injury (4/10), resolved the lameness in all horses re-evaluated by a veterinarian (9/9) and allowed return to full athletic function in all cases at long-term follow up (median 5 years; range 1.25-9 years). CONCLUSION: Tenoscopic decompression was an effective treatment for DFTS synoviocoeles, which, along with treatment of concurrent intrathecal injury, carried an excellent prognosis and avoided the need for resection via an extrasynovial approach.
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Doenças dos Cavalos , Animais , Descompressão/veterinária , Membro Anterior , Doenças dos Cavalos/diagnóstico por imagem , Doenças dos Cavalos/cirurgia , Cavalos , Coxeadura Animal/diagnóstico por imagem , Coxeadura Animal/cirurgia , Estudos Retrospectivos , Ultrassonografia de Intervenção/veterináriaRESUMO
Cytomegalovirus (CMV) induction of large frequencies of highly functional memory T cells has attracted much interest in the utility of CMV-based vaccine vectors, with exciting preclinical data obtained in models of infectious diseases and cancer. However, pathogenesis of human CMV (HCMV) remains a concern. Attenuated CMV-based vectors, such as replication- or spread-deficient viruses, potentially offer an alternative to fully replicating vectors. However, it is not well understood how CMV attenuation impacts vector immunogenicity, particularly when administered via relevant routes of immunization such as the skin. Herein, we used the murine cytomegalovirus (MCMV) model to investigate the impact of vector attenuation on T-cell memory formation following subcutaneous administration. We found that the spread-deficient virus (ΔgL-MCMV) was impaired in its ability to induce memory CD8+ T cells reactive to some (M38, IE1) but not all (IE3) viral antigens. Impaired-memory T-cell development was associated with a preferential and pronounced loss of polyfunctional (IFN-γ+ TNF-α+ ) T cells and also reduced accumulation of TCF1+ T cells, and was not rescued by increasing the dose of replication-defective MCMV. Finally, whilst vector attenuation reduced dendritic cell (DC) recruitment to skin-draining lymph nodes, systematic depletion of multiple DC subsets during acute subcutaneous MCMV infection had a negligible impact on T-cell memory formation, implying that attenuated responses induced by replication-deficient vectors were likely not a consequence of impaired initial DC activation. Thus, overall, these data imply that the choice of antigen and/or cloning strategy of exogenous antigen in combination with the route of immunization may influence the ability of attenuated CMV vectors to induce robust functional T-cell memory.
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Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Células Dendríticas/imunologia , Memória Imunológica/imunologia , Pele/imunologia , Replicação Viral/imunologia , Animais , Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/virologia , Infecções por Citomegalovirus/virologia , Células Dendríticas/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pele/virologiaRESUMO
Recognition of influenza A virus (IAV) by the innate immune system triggers pathways that restrict viral replication, activate innate immune cells, and regulate adaptive immunity. However, excessive innate immune activation can exaggerate disease. The pathways promoting excessive activation are incompletely understood, with limited experimental models to investigate the mechanisms driving influenza virus-induced inflammation in humans. Interferon regulatory factor 5 (IRF5) is a transcription factor that plays important roles in the induction of cytokines after viral sensing. In an in vivo model of IAV infection, IRF5 deficiency reduced IAV-driven immune pathology and associated inflammatory cytokine production, specifically reducing cytokine-producing myeloid cell populations in Irf5-/- mice but not impacting type 1 interferon (IFN) production or virus replication. Using cytometry by time of flight (CyTOF), we identified that human lung IRF5 expression was highest in cells of the myeloid lineage. To investigate the role of IRF5 in mediating human inflammatory responses by myeloid cells to IAV, we employed human-induced pluripotent stem cells (hIPSCs) with biallelic mutations in IRF5, demonstrating for the first time that induced pluripotent stem cell-derived dendritic cells (iPS-DCs) with biallelic mutations can be used to investigate the regulation of human virus-induced immune responses. Using this technology, we reveal that IRF5 deficiency in human DCs, or macrophages, corresponded with reduced virus-induced inflammatory cytokine production, with IRF5 acting downstream of Toll-like receptor 7 (TLR7) and, possibly, retinoic acid-inducible gene I (RIG-I) after viral sensing. Thus, IRF5 acts as a regulator of myeloid cell inflammatory cytokine production during IAV infection in mice and humans and drives immune-mediated viral pathogenesis independently of type 1 IFN and virus replication.IMPORTANCE The inflammatory response to influenza A virus (IAV) participates in infection control but contributes to disease severity. After viral detection, intracellular pathways are activated, initiating cytokine production, but these pathways are incompletely understood. We show that interferon regulatory factor 5 (IRF5) mediates IAV-induced inflammation and, in mice, drives pathology. This was independent of antiviral type 1 IFN and virus replication, implying that IRF5 could be specifically targeted to treat influenza virus-induced inflammation. We show for the first time that human iPSC technology can be exploited in genetic studies of virus-induced immune responses. Using this technology, we deleted IRF5 in human myeloid cells. These IRF5-deficient cells exhibited impaired influenza virus-induced cytokine production and revealed that IRF5 acts downstream of Toll-like receptor 7 and possibly retinoic acid-inducible gene I. Our data demonstrate the importance of IRF5 in influenza virus-induced inflammation, suggesting that genetic variation in the IRF5 gene may influence host susceptibility to viral diseases.
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Células-Tronco Pluripotentes Induzidas/imunologia , Vírus da Influenza A/imunologia , Fatores Reguladores de Interferon/metabolismo , Imunidade Adaptativa/fisiologia , Animais , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/fisiologia , Vírus da Influenza A/metabolismo , Vírus da Influenza A/fisiologia , Influenza Humana/imunologia , Fatores Reguladores de Interferon/imunologia , Interferon Tipo I/metabolismo , Pulmão/virologia , Macrófagos/virologia , Camundongos , Infecções por Orthomyxoviridae/virologia , Replicação Viral/fisiologiaRESUMO
There are no licensed vaccines for human cytomegalovirus (HCMV), and current antiviral drugs that target viral proteins are toxic and prone to resistance. Targeting host pathways essential for virus replication provides an alternate strategy that may reduce opportunities for drug resistance to occur. Oxidative stress is triggered by numerous viruses including HCMV. Peroxynitrite is a reactive nitrogen species that is formed during oxidative stress. Herein, we identified that HCMV rapidly induces the generation of intracellular peroxynitrite upon infection in a manner partially dependent upon xanthine oxidase generation. Peroxynitrite promoted HCMV infection in both cell-free and cell-associated infection systems in multiple cell types. Inhibiting peroxynitrite within the first 24 hours of infection prevented HCMV replication and peroxynitrite promoted cell entry and pp65 translocation into the host cell nuclei. Furthermore, using the murine cytomegalovirus model, we demonstrated that antagonizing peroxynitrite significantly reduces cytomegalovirus replication and pathogenesis in vivo. Overall, our study highlights a proviral role for peroxynitrite in CMV infection and implies that RNS and/or the mechanisms that induce their production could be targeted as a novel strategy to inhibit HCMV infection. IMPORTANCE: Human cytomegalovirus (HCMV) causes significant disease in individuals with impaired or immature immune systems, such as transplant patients and after congenital infection. Antiviral drugs that target the virus directly are toxic and are susceptible to antiviral drug resistance due to virus mutations. An alternate strategy is to target processes within host cells that are required by the virus for replication. Herein, we show that HCMV infection triggers a highly reactive molecule, peroxynitrite, during the initial stages of infection. Peroxynitrite was required for the initial entry of the virus into the cell and promotes virus replication in multiple cell types, suggesting a broad pro-viral function. Importantly, targeting peroxynitrite dramatically inhibited cytomegalovirus replication in cells in the laboratory and in mice, suggesting that therapeutic targeting of this molecule and/or the cellular functions it regulates could represent a novel strategy to inhibit HCMV infection.
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Infecções por Citomegalovirus , Citomegalovirus , Modelos Animais de Doenças , Ácido Peroxinitroso , Internalização do Vírus , Replicação Viral , Ácido Peroxinitroso/metabolismo , Ácido Peroxinitroso/farmacologia , Animais , Camundongos , Citomegalovirus/fisiologia , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/genética , Internalização do Vírus/efeitos dos fármacos , Humanos , Infecções por Citomegalovirus/virologia , Replicação Viral/efeitos dos fármacos , Muromegalovirus/fisiologia , Muromegalovirus/efeitos dos fármacos , Linhagem Celular , Estresse OxidativoRESUMO
Consistency in medical decision-making is ideally expected. This includes consistency between different clinicians so that the same patient will receive the same diagnosis regardless of the assessing clinician. It also encompasses reliability as an individual clinician meaning at any given time or context, we apply the same process and principles to ensure the decisions we make do not deviate significantly from our peers or indeed our own past decisions. However, consistency in decision-making can be challenged when working within a busy healthcare system. We discuss the concept of 'noise' and explore how it affects decision-making in acute presentations of transient neurology where doctors can differ in terms of their diagnostic decisions.
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Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Ataque Isquêmico Transitório/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Reprodutibilidade dos TestesRESUMO
BACKGROUND: In-hospital stroke refers to a stroke arising in a patient during hospital admission for another condition. Between 2 and 17% of all inpatient strokes are in-hospital strokes. AIM: To compare the outcomes and performance on quality-of-care stroke measures of in-hospital stroke cases with community-onset strokes. METHODS: Data collected for the Irish Annual Audit of Stroke from an Irish university teaching hospital was analysed for a 2-year period from 1st January 2020 to 31st December 2021. A retrospective cohort study was conducted to compare baseline characteristics, outcomes, and performance on standardised quality-of-care measures between the cohorts. RESULTS: The rate of IHS was 15.6%. Median age was 73 years and 72 years for in-hospital and community-onset strokes respectively. Amongst in-hospital strokes, COVID-19 co-diagnosis (9.1% versus 1.3%; p = .0004), admission to intensive care (52.3% versus 5.3%; p < .0001), discharge to long term care (6.8% versus 2.3%; p = .04), mortality (12.5% versus 7.6%; p = .13), and modified Rankin score of two or more at discharge (58.0% versus 38.1%; p = .001), were more likely compared to community-onset strokes. Thrombolysis rates were lower (7.3% versus 12.0%; p = .22) and thrombectomy rates higher (9.8% versus 6.6;% p = .32), albeit non-significantly. Median time to thrombolysis was slower amongst in-hospital strokes (105 min versus 66 min; p = .03) and they were less likely to be admitted to the stroke unit (43.2% versus 78.5%; p < .0001). CONCLUSIONS: When compared with community-onset stroke, in-hospital stroke represents a distinct stroke subgroup with poorer outcomes and delays to thrombolysis emphasising the need for standardised approaches to evaluation and management.
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BACKGROUND: Influenza vaccination will have added importance this winter given the possibility of further waves of the COVID-19 pandemic. This study examines the impact of an electronic medical record (EMR) reminder on influenza vaccine uptake among eligible hospital inpatients. METHODS: We included a convenience sample of 750 adults (median age 77 years) who are eligible for influenza vaccination (⩾65 years and/or length of stay >30 days). A live electronic dashboard identified patients eligible for vaccination, prompting reminders sent to the clinical teams via the EMR. RESULTS: The EMR reminder was associated with almost a 50% higher likelihood of vaccination after adjusting for other covariates (odds ratio 1.48 (95% confidence interval 1.00-2.20); p = 0.048). DISCUSSION: Reminders sent to the clinical team via the EMR appear to be an effective means of increasing vaccine uptake and should be considered as part of this year's drive to vaccinate eligible patients in hospital.
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COVID-19 , Influenza Humana , Adulto , Humanos , Idoso , Influenza Humana/prevenção & controle , Pacientes Internados , Registros Eletrônicos de Saúde , Pandemias , Sistemas de Alerta , VacinaçãoRESUMO
Inhibitory CD4+ T cells have been linked with suboptimal immune responses against cancer and pathogen chronicity. However, the mechanisms that underpin the development of these regulatory cells, especially in the context of ongoing antigen exposure, have remained obscure. To address this knowledge gap, we undertook a comprehensive functional, phenotypic, and transcriptomic analysis of interleukin (IL)-10-producing CD4+ T cells induced by chronic infection with murine cytomegalovirus (MCMV). We identified these cells as clonally expanded and highly differentiated TH1-like cells that developed in a T-bet-dependent manner and coexpressed arginase-1 (Arg1), which promotes the catalytic breakdown of L-arginine. Mice lacking Arg1-expressing CD4+ T cells exhibited more robust antiviral immunity and were better able to control MCMV. Conditional deletion of T-bet in the CD4+ lineage suppressed the development of these inhibitory cells and also enhanced immune control of MCMV. Collectively, these data elucidated the ontogeny of IL-10-producing CD4+ T cells and revealed a previously unappreciated mechanism of immune regulation, whereby viral persistence was facilitated by the site-specific delivery of Arg1.
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Citomegalovirus , Muromegalovirus , Camundongos , Animais , Interleucina-10 , Linfócitos T CD4-Positivos , Arginase/genética , Muromegalovirus/fisiologiaRESUMO
BACKGROUND: Amphetamine use causes cardiomyopathy via catecholamine-mediated effects such as tachycardia, hypertension, vasoconstriction, and direct cardio-toxic effects. Traditionally, an increased risk of haemorrhagic stroke is associated with amphetamine use. However, up to one-third of stimulant-associated cardiomyopathy patients have left ventricular (LV) thrombus formation leading to an increased risk of systemic embolization. We report a case of amphetamine-induced cardiomyopathy complicated by embolic stroke secondary to LV thrombus. CASE SUMMARY: A 38-year-old man with 6-month history of sustained amphetamine use presented to the emergency department with left-sided weakness, facial droop, and dysarthria. Angiography confirmed right middle cerebral artery thrombus. Prompt mechanical thrombectomy yielded full neurological recovery. Dyspnoea prompted transthoracic echocardiography showing dilated cardiomyopathy with an ejection fraction of 5% and LV thrombus. Anticoagulation was initiated with warfarin as well as pharmacological therapy for heart failure with reduced ejection fraction including bisoprolol, spironolactone, loop diuretic, and sacubitril/valsartan. He was discharged successfully following resolution of ventricular thrombus and medical management of heart failure. Clinical recovery was hampered by psychosocial factors resulting in non-adherence to medical therapy and continued amphetamine use. CONCLUSION: Sustained amphetamine use can result in severe dilated cardiomyopathy with LV thrombus formation and embolic complications such as ischaemic stroke. Avoidance of amphetamines in conjunction with guideline-directed pharmacological management are key components of therapy. However, psychosocial factors can exert significant influence on recovery.
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Mieloma Múltiplo/complicações , Púrpura Trombocitopênica Idiopática/complicações , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Mieloma Múltiplo/tratamento farmacológico , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to identify risk factors for self-harm for children and adolescents in a mental health inpatient unit. METHODS: A retrospective file audit of patient files over three years (2006-2009) was conducted to determine risk factors associated with self-harm in children and adolescents admitted to a mental health unit. A checklist of potential factors was based on risk factors found in a review of the literature including demographic information, diagnosis, home situation, environmental stressors, childhood trauma and previous mental health care. The study compared those who self-harmed with a control group who did not self-harm. RESULTS: There were 150 patients who self-harmed (mean age 14 years) and 56 patients who did not self-harm with a mean age of 13 years. Several factors were identified that increased the likelihood of self-harm, including a diagnosis of depression, female gender, increasing age, being Australian-born, living with a step parent, not having received previous mental health care, having a history of trauma, and having other stressors including problems within the family. CONCLUSIONS: While increasing age, female gender, a history of trauma and a diagnosis of depression are well known as risk factors for self-harm, this study confirms that family factors, in particular living with a step parent, significantly add to the risk. Child and adolescent services should be aware of the increased risk of self-harm in young people with mental health problems who live in blended families. Treatment approaches need to involve parents as well as the child or young person.
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Pacientes Internados/psicologia , Transtornos Mentais/psicologia , Comportamento Autodestrutivo/psicologia , Adolescente , Criança , Depressão/psicologia , Feminino , Hospitalização , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Ideação SuicidaRESUMO
OBJECTIVE: The aim of this paper is to describe trends in aggression and self harm on a mental health inpatient unit for children and adolescents between January 2006 and August 2009. Various ward interventions and the ward milieu were evaluated as possible explanatory factors for trends. METHOD: This was a retrospective study whereby incidents of aggression, self harm and seclusion were obtained from a computerized Incident Information Management System (IIMS) database. Trends in incidents were analysed using linear regression analyses. RESULTS: Over a 44-month period, 292 incidents of aggression and 139 incidents of self harm were reported. The use of seclusion and the number of aggressive incidents both significantly decreased over time. Trends suggested a positive relationship between the introduction of restraint training, changes in leadership and full staff complement, and a reduction in aggression and seclusion. CONCLUSIONS: Although the findings are limited by their retrospective nature and reliance on formal records, this study suggests that different factors can contribute to decrease the incidence of adverse events on a psychiatric ward. Future prospective research is needed to assess the effectiveness of different interventions in both the prevention and management of self harm, aggression and seclusion in child and adolescent inpatient units.
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Agressão/psicologia , Unidade Hospitalar de Psiquiatria , Comportamento Autodestrutivo/psicologia , Adolescente , Terapia Comportamental , Criança , Interpretação Estatística de Dados , Feminino , Humanos , Modelos Lineares , Masculino , Recursos Humanos em Hospital , Estudos Retrospectivos , Comportamento Autodestrutivo/epidemiologia , Comportamento Social , Fatores de Tempo , Recursos HumanosRESUMO
An adrenal incidentaloma is a mass found incidentally on radiological imaging performed for other reasons. The prevalence of these incidentalomas increases with age, and they all must be evaluated to determine if they are benign or malignant and if they are functioning or non-functioning. A 71-year-old female presented with sub-acute bilateral lower limb pitting edema and dyspnoea. Imaging showed an 8 cm smoothly defined heterogeneous right adrenal mass and a number of low attenuation lesions throughout the liver. This case report describes a rare presentation of adrenocortical carcinoma due to an adrenal incidentaloma identified on imaging in a patient presenting with bilateral lower limb edema. The laboratory and imaging evaluation of these incidentalomas are also discussed.
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INTRODUCTION: Use of web-based messaging applications to communicate clinical information is common between non-consultant hospital doctors (NCHDs). This study sought to assess web-based messenger use in NCHDs following the introduction of a more secure alternative to WhatsApp (WhatsApp, Inc., Menlo Park, CA, USA). METHODS: A 10-item survey was undertaken on two NCHD cohorts. The second cohort received training on data protection and an alternative application to WhatsApp. Quantitative data analysis was conducted using the IBM Statistical Package for Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY). RESULTS: The total response rate across both groups was 63% (N = 68). The majority of respondents used WhatsApp to communicate clinical information. In the second cohort, fewer NCHDs shared identifiable sensitive patient information 97% (n = 29/30) vs 81% (n = 25/31) and fewer NCHDs shared/stored clinical images. DISCUSSION: WhatsApp use is common among NCHDs. An alternative means of communication can improve the safety of patient data. NCHDs require more training on data protection laws and their own responsibilities.
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Interferon lambda (IFNλ) is a group of cytokines that belong to the IL-10 family. They exhibit antiviral activities against certain viruses during infection of the liver and mucosal tissues. Here we report that IFNλ restricts in vitro replication of the ß-herpesvirus murine cytomegalovirus (mCMV). However, IFNλR1-deficient (Ifnλr1-/-) mice were not preferentially susceptible to mCMV infection in vivo during acute infection after systemic or mucosal challenge, or during virus persistence in the mucosa. Instead, our studies revealed that IFNλ influences NK cell responses during mCMV infection. Ifnλr1-/- mice exhibited defective development of conventional interferon-gamma (IFNγ)-expressing NK cells in the spleen during mCMV infection whereas accumulation of granzyme B-expressing NK cells was unaltered. In vitro, development of splenic IFNγ+ NK cells following stimulation with IL-12 or, to a lesser extent, IL-18 was abrogated by IFNλR1-deficiency. Thus, IFNλ regulates NK cell responses during mCMV infection and restricts virus replication in vitro but is redundant in the control of acute and persistent mCMV replication within mucosal and non-mucosal tissues.
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Infecções por Herpesviridae/imunologia , Interferon gama/metabolismo , Interferons/metabolismo , Células Matadoras Naturais/imunologia , Muromegalovirus/imunologia , Animais , Feminino , Técnicas In Vitro , Células Matadoras Naturais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Muromegalovirus/fisiologia , Replicação ViralRESUMO
OBJECTIVE: Recovery from anorexia nervosa is confounded by intrusive anorectic cognitions and rituals. It has been observed that olanzapine, an atypical antipsychotic, can reduce this anorexic rumination. A pilot study was designed to test the effectiveness of olanzapine in this role. METHODS: A randomized trial of olanzapine versus chlorpromazine, with anorexic rumination as the primary outcome, was conducted. Of the 26 patients who presented, 15 were randomized in a balanced block design, eight to olanzapine and seven to chlorpromazine. RESULTS: Only the olanzapine group had a significant reduction in the degree of rumination. CONCLUSION: Olanzapine may be of benefit in anorexia nervosa by causing a reduction in anorexic rumination.