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BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.
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Acetilcisteína , Bronquiectasia , Adulto , Humanos , Masculino , Idoso , Acetilcisteína/efeitos adversos , Qualidade de Vida , Projetos Piloto , Bronquiectasia/tratamento farmacológico , Inflamação/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Método Duplo-CegoRESUMO
We tested the hypothesis that water Ca2+ is involved in control of branchial Na+ permeability in low pH tolerant convict cichlids and black neon tetras. We measured Na+ efflux in water with different Ca2+ concentrations during exposure to low pH, silver, and copper, at levels which are known to stimulate Na+ efflux. For convict cichlids at pH 7.5 exposure to 0 µmol L-1 Ca2+caused Na+ efflux to rise 2.5 times above controls at 100 µmol L-1 Ca2+. However, raising [Ca2+] to 500 µmol L-1 had no effect. Upon exposure to pH 3.5 (control [Ca2+]) Na+ efflux rose almost 5× and increasing the [Ca2+] 5-fold did not reduce the magnitude of stimulation. Exposure to 1 µmol L-1 silver and 25 µmol L-1 copper stimulated Na+ efflux 7×, and 2×, respectively. Raising [Ca2+] concentration during metal exposure halved the stimulation of Na+ efflux caused by silver, and eliminated the stimulation elicited by copper. For black neon tetras raising or lowering water [Ca2+] had no effect on Na+ efflux at pH 7.5. Exposure to pH 3.5 caused Na+ efflux to rise 2.5× but changing [Ca2+] had no effect. Exposure to 1 µmol L-1 silver, or 25 µmol L-1 copper caused Na+ efflux of tetras to rise 4-fold and 3-fold, respectively. Raising [Ca2+] during silver exposure reduced the stimulation of Na+ efflux by about 50%, but during copper exposure increased [Ca2+] had no effect on stimulation of Na+ efflux. These results suggest water Ca2+ plays a role in control of branchial Na+ permeability in cichlids, but perhaps not tetras. In addition, the silver and copper concentrations required to inhibit Na+ uptake and stimulate Na+ efflux were higher than the concentrations used on non-characids and non-cichlids, which indicates that our fish are much more tolerant of these metals.
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Characidae , Ciclídeos , Animais , Ciclídeos/fisiologia , Cálcio , Água , Cobre , Prata/farmacologia , Neônio/farmacologia , Sódio , Permeabilidade , BrânquiasRESUMO
BACKGROUND: There are long patient waiting lists for specialist care. A dermatology dialogue service between primary and secondary care (DDPS) was developed in eastern England. Primary care referrers uploaded patient images of skin conditions for review by and dialogue with consultant dermatologists in an attempt to retain patients in primary care rather than refer them to secondary care. METHODS: Evaluation of service performance against specific targets, including reduction in secondary care waiting list growth over the period April 2021-March 2022 inclusive. Service activity was summarized in terms of speed of resolution, case numbers, and dispositions. Clinician and patient satisfaction were assessed using structured questionnaires. Actual numbers of new referrals were compared to projections based on historical data. Waiting list growth was compared to other specialties and other commissioning areas. Waiting times to initial treatment were monitored. RESULTS: Over 3300 patients were enrolled andâ¯>â¯90% of dialogues were resolved within 36 hours. Clinician and patient satisfaction were high. Frequently asked questions and conditions were highlighted by dermatologists to design and deliver an educational event for primary care clinicians that was well received. Waiting list growth for dermatology patients in the commissioning area was smaller than for other major specialties, and generally smaller than growth for dermatology waiting lists commissioned by other NHS commissioners. There was no negative impact on the urgent priority (cancer pathway) waiting list. CONCLUSION: The DDPS was satisfactory for clinicians and patients and coincided with lower growth in dermatology waiting lists than might otherwise have been expected.
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Dermatologia , Satisfação do Paciente , Atenção Primária à Saúde , Encaminhamento e Consulta , Atenção Secundária à Saúde , Listas de Espera , Humanos , Inglaterra , Dermatopatias/terapia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The standard treatment for regional failure in nasopharyngeal carcinoma (NPC) is the radical neck dissection (RND). Our study sought to determine if magnetic resonance imaging (MRI) may accurately predict nodal involvement to allow selected levels of neck dissection to be preserved. STUDY DESIGN AND SETTING: We analysed retrospectively all NPC patients in our centre undergoing neck dissections as salvage therapy for nodal recurrence. Nodal involvement based on the preoperative MRI was assessed and compared with postoperative histopathology. METHODS: This is a retrospective study conducted on patients in our centre with recurrent NPC from February 2002 to February 2017. Patients were identified from the database of the otolaryngology oncology division at our institution. Of these, 28 patients met all our inclusion and exclusion criteria. We calculated sensitivity and specificity as well as average number of nodes per patient. RESULTS: In our study, we calculated the false negative and false positive rates of preoperative MRI neck by levels. Overall sensitivity of MRI picking up disease by level was 76% and specificity was 86%. CONCLUSION: Based on our study, we will be missing a total of 10 (7.1%) diseased neck levels in eight (28.5%) patients. MRI alone, therefore, does not provide enough information to allow safe selective preservation of neck levels in surgical salvage of neck recurrences in NPC.
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Neoplasias Nasofaríngeas , Esvaziamento Cervical , Humanos , Esvaziamento Cervical/métodos , Carcinoma Nasofaríngeo/cirurgia , Estudos Retrospectivos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/cirurgia , Neoplasias Nasofaríngeas/patologia , Terapia de Salvação , Recidiva Local de Neoplasia/cirurgia , Metástase LinfáticaRESUMO
'openFrame' is a modular, low-cost, open-hardware microscopy platform that can be configured or adapted to most light microscopy techniques and is easily upgradeable or expandable to multiple modalities. The ability to freely mix and interchange both open-source and proprietary hardware components or software enables low-cost, yet research-grade instruments to be assembled and maintained. It also enables rapid prototyping of advanced or novel microscope systems. For long-term time-lapse image data acquisition, slide-scanning or high content analysis, we have developed a novel optical autofocus incorporating orthogonal cylindrical optics to provide robust single-shot closed-loop focus lock, which we have demonstrated to accommodate defocus up to ±37 µm with <200 nm accuracy, and a two-step autofocus mode which we have shown can operate with defocus up to ±68 µm. We have used this to implement automated single molecule localisation microscopy (SMLM) in a relatively low-cost openFrame-based instrument using multimode diode lasers for excitation and cooled CMOS cameras.
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There are many causes of cauda equina (CE) thickening on neuroimaging of the lumbar spine. The imaging features of CE thickening for the various conditions often overlap and are non-specific to clinch a definite diagnosis. Hence, the imaging findings have to be discerned in accordance with the patient's presenting history, clinical examination findings, and results from electrophysiology and laboratory studies. In this review, the authors aim to supplement the existing literature on imaging findings of CE thickening with a diagnostic framework for clinical workup. The authors also aim to familiarise readers with the interpretation of CE thickening on magnetic resonance imaging (MRI) and would like to illustrate the normal variants and pitfalls that could be mistaken for abnormal results.
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Cauda Equina , Humanos , Cauda Equina/diagnóstico por imagem , Cauda Equina/patologia , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Vértebras Lombares/diagnóstico por imagem , Região LombossacralRESUMO
OBJECTIVE: Age at menarche and the interval between menarche and age at first vaginal birth have been shown to be associated with reproductive performance; however, their association with maternal birth trauma has not been studied. We aimed to determine whether age at menarche, age at first vaginal birth and their interval are associated independently with levator ani muscle (LAM) avulsion and external anal sphincter (EAS) defect. METHODS: This was a retrospective analysis of the ultrasound volume datasets of 466 vaginally parous patients attending one of two tertiary urogynecological units in Australia. All patients had undergone a standardized interview and clinical examination using the pelvic organ prolapse quantification staging system, followed by four-dimensional translabial ultrasound. Tomographic ultrasound imaging was used to evaluate the LAM for avulsion and the EAS for significant defect. RESULTS: Of the 466 women analyzed, LAM avulsion was diagnosed in 121 (26.0%) and significant EAS defect in 55 (11.8%). Logistic regression analysis showed no association between age at menarche and LAM avulsion (P = 0.67). Weak but significant associations were noted between LAM avulsion and age at first vaginal birth (odds ratio (OR), 1.070 (95% CI, 1.03-1.11); P = 0.0007) and between LAM avulsion and menarche-to-first-vaginal-birth interval (OR, 1.064 (95% CI, 1.02-1.11); P = 0.0018). No significant associations were noted between significant EAS defect and any of the evaluated variables (all P ≥ 0.49). CONCLUSIONS: Age at menarche is not predictive of maternal birth trauma i.e. LAM avulsion and EAS residual defect. There was a statistically significant association between LAM avulsion and menarche-to-first-vaginal-birth interval; however, this was not stronger than the previously established association between LAM avulsion and age at first vaginal birth, arguing against any distinct effect of prolonged prepregnancy hormonal stimulation on the biomechanical properties of the pelvic floor. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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Menarca , Prolapso de Órgão Pélvico , Canal Anal/diagnóstico por imagem , Parto Obstétrico/métodos , Feminino , Humanos , Masculino , Parto , Diafragma da Pelve/diagnóstico por imagem , Diafragma da Pelve/lesões , Prolapso de Órgão Pélvico/diagnóstico por imagem , Prolapso de Órgão Pélvico/epidemiologia , Prolapso de Órgão Pélvico/etiologia , Gravidez , Estudos Retrospectivos , Ultrassonografia/métodosRESUMO
Autoimmune encephalitis (AE) can present like a psychiatric disorder. We aimed to illustrate the psychiatric manifestations, course and management of AE in a paediatric cohort. Neuropsychiatric symptoms, investigations and treatment were retrospectively retrieved in 16 patients (mean age 11.31, SD 2.98) with an AE diagnosis at the liaison psychiatry services in two UK tertiary paediatric centres. Psychiatric presentation was characterised by an acute polysymptomatic (predominantly agitation, anger outbursts/aggressiveness, hallucinations, and emotional lability) onset. Antipsychotics produced side effects and significant worsening of symptoms in four cases, and benzodiazepines were commonly used. This psychiatric phenotype should make clinicians suspect the diagnosis of AE and carefully consider use of treatments.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Doença de Hashimoto , Transtornos Mentais , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Criança , Alucinações , Doença de Hashimoto/diagnóstico , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/etiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Macroprolactinaemia is usually detected by polyethylene glycol (PEG) precipitation in clinical laboratories. Laboratory data on prolactin and macroprolactin screening by PEG precipitation in a tertiary hospital were reviewed in order to revise the local policy for reflex screening and reporting of macroprolactin in patients with hyperprolactinaemia. MATERIALS AND METHODS: Paired prolactin results from 464 patients before and after PEG precipitation, either requested by a clinician or performed as a reflex test, were retrieved and reviewed. RESULTS: Recovery of prolactin after PEG treatment was highly variable (3.7 to 97.7%). The distribution of prolactin recovery percentages after PEG precipitation in patients with true hyperprolactinaemia was markedly different from that in patients without true hyperprolactinaemia. The proportion of patients with true hyperprolactinaemia increased gradually with increasing pre-PEG prolactin concentrations; the reverse was true with macroprolactinaemia. Five patients (1.1%) were found to have co-existing macroprolactinaemia and true hyperprolactinaemia. CONCLUSION: Results from this retrospective study indicate that macroprolactinaemia is common and can be present even in patients with very high serum prolactin concentrations. There is no cut-off limit for pre-PEG serum prolactin concentration that can totally exclude macroprolactinaemia. Moreover, co-existence of true hyperprolactinaemia and macroprolactinaemia in the same patient is not a rare phenomenon. Post-PEG prolactin concentration and percentage recovery should be reported together to guide the interpretation and management of hyperprolactinaemia.
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Hiperprolactinemia , Humanos , Hiperprolactinemia/diagnóstico , Programas de Rastreamento , Polietilenoglicóis , Prolactina , Estudos RetrospectivosRESUMO
Decades of research and policy interventions on biodiversity have insufficiently addressed the dual issues of biodiversity degradation and social justice. New approaches are therefore needed. We devised a research and action agenda that calls for a collective task of revisiting biodiversity toward the goal of sustaining diverse and just futures for life on Earth. Revisiting biodiversity involves critically reflecting on past and present research, policy, and practice concerning biodiversity to inspire creative thinking about the future. The agenda was developed through a 2-year dialogue process that involved close to 300 experts from diverse disciplines and locations. This process was informed by social science insights that show biodiversity research and action is underpinned by choices about how problems are conceptualized. Recognizing knowledge, action, and ethics as inseparable, we synthesized a set of principles that help navigate the task of revisiting biodiversity. The agenda articulates 4 thematic areas for future research. First, researchers need to revisit biodiversity narratives by challenging conceptualizations that exclude diversity and entrench the separation of humans, cultures, economies, and societies from nature. Second, researchers should focus on the relationships between the Anthropocene, biodiversity, and culture by considering humanity and biodiversity as tied together in specific contexts. Third, researchers should focus on nature and economies by better accounting for the interacting structures of economic and financial systems as core drivers of biodiversity loss. Finally, researchers should enable transformative biodiversity research and action by reconfiguring relationships between human and nonhuman communities in and through science, policy, and practice. Revisiting biodiversity necessitates a renewed focus on dialogue among biodiversity communities and beyond that critically reflects on the past to channel research and action toward fostering just and diverse futures for human and nonhuman life on Earth.
Una Agenda para la Investigación y la Acción hacia un Futuro Diverso y Justo para la Vida sobre la Tierra Resumen Las décadas de investigación e intervenciones políticas sobre la biodiversidad han tratado significativamente los temas de la degradación de la biodiversidad y la justicia social. Debido a esto, se requieren nuevas estrategias. Diseñamos una agenda de investigación y acción que llama a la labor colectiva de revisar la biodiversidad hacia el objetivo de sustentar un futuro diverso y justo para la vida sobre la Tierra. Cuando se revisa la biodiversidad, se requiere de una reflexión crítica sobre las investigaciones, políticas y prácticas presentes y pasadas sobre la biodiversidad para inspirar un pensamiento creativo acerca del futuro. Desarrollamos la agenda por medio de un proceso de diálogo de dos años que involucró a casi 300 expertos de diversas disciplinas y localidades. Este proceso estuvo orientado por el conocimiento de las ciencias sociales que muestra cómo la investigación y la acción para la biodiversidad están sostenidas por las opciones de cómo están conceptualizados los problemas. Reconocimos al conocimiento, la acción y la ética como inseparables y sintetizamos un conjunto de principios que ayuda a navegar la labor de revisar la biodiversidad. La agenda articula cuatro áreas temáticas para la investigación en el futuro. Primero, los investigadores necesitan revisar las narrativas de la biodiversidad mediante el cuestionamiento de las conceptualizaciones que excluyen a la diversidad y consolidan la separación entre humanos, culturas, economías y sociedades y la naturaleza. Segundo, los investigadores deberían enfocarse en las relaciones entre el antropoceno, la biodiversidad y la cultura al considerar a la humanidad y la biodiversidad como interconectadas en contextos específicos. Tercero, los investigadores deberían enfocarse en la naturaleza y las economías al tener en mejor cuenta la interacción de las estructuras de los sistemas económico y financiero como conductores nucleares de la pérdida de la biodiversidad. Finalmente, los investigadores deberían permitir la investigación y acción transformadoras de la biodiversidad al reconfigurar las relaciones entre las comunidades humanas y no humanas dentro y a través de la ciencia, la política y la práctica. La revisión de la biodiversidad necesita de un enfoque renovado sobre el diálogo entre las comunidades de la biodiversidad y más allá, que reflexione críticamente sobre el pasado para canalizar a la investigación y acción hacia el fomento del futuro justo y diverso para la vida humana y no humana sobre la Tierra.
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Biodiversidade , Conservação dos Recursos Naturais , Previsões , Humanos , Justiça SocialRESUMO
PURPOSE: To investigate the prevalence and epidemiological risk factors of olfactory and/or taste disorder (OTD), in particular isolated OTD, in patients with laboratory-confirmed COVID-19 infection. METHODS: We conducted a retrospective and cross-sectional study. Patients with laboratory-confirmed COVID-19 infection were recruited from the National Centre for Infectious Diseases (NCID) Singapore between 24 March 2020 and 16 April 2020. The electronic health records of these patients were accessed, and demographic data and symptoms reported (respiratory, self-reported OTD and other symptoms such as headache, myalgia and lethargy) were collected. RESULTS: A total of 1065 patients with laboratory-confirmed COVID-19 were recruited. Overall, the prevalence of OTD was 12.6%. Twelve patients (1.1%) had isolated OTD. The top three symptoms associated with OTD were cough, fever and sore throat. The symptoms of runny nose and blocked nose were experienced by only 29.8 and 19.3% of patients, respectively. Multivariate analysis demonstrated that the female gender, presence of blocked nose and absence of fever were significantly associated with OTD (adjusted relative risks 1.77, 3.31, 0.42, respectively). All these factors were statistically significant. CONCLUSION: Patients with COVID-19 infection can present with OTD, either in isolation or in combination with other general symptoms. Certain demographic profile, such as being female, and symptomatology such as the presence of blocked nose and absence of fever, were more likely to have OTD when infected by COVID-19. Further studies to elucidate the pathophysiology of OTD in these patients will be beneficial.
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COVID-19 , Transtornos do Olfato , Estudos Transversais , Feminino , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Singapura/epidemiologia , Distúrbios do PaladarRESUMO
COVID-19 has affected every walk of life, including the healthcare sector. In this article, we discuss how an Otolaryngology department in a tertiary hospital in Singapore had to adapt to the pandemic in areas of outpatient care, elective surgeries, personal protection, residency training, education and research. Documenting our experience has helped us to understand the areas of work which can be affected in a pandemic and the factors that have helped to mitigate disruption. This will prove useful in our approach to subsequent pandemics.
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COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Singapura , Centros de Atenção TerciáriaRESUMO
OBJECTIVE: Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years. METHOD: Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan-Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression. RESULTS: There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/106. Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4-7.2] and PM (SIR 3.5, 95% CI 1.8-7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13-4.70) and PM patients (HR 2.10, 95% CI 1.03-4.27) compared with the general population with CVD. CONCLUSION: We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.
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Doenças Cardiovasculares/mortalidade , Miosite/complicações , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Adulto JovemRESUMO
PURPOSE: Loneliness is a challenge for individuals with psychosis; however, interventions rarely target loneliness in this group. METHOD: We developed a pilot positive psychology group intervention designed to reduce loneliness in psychosis and examined its feasibility and acceptability. RESULTS: Sixteen participants attended 5.38 (SD = 0.70) out of six sessions, with a dropout rate of 10%. Participants were significantly less lonely at post-treatment (p < 0.001, d = 1.51), and maintained their improvements from post-treatment to follow-up (p = 0.81, d = 0.07). CONCLUSIONS: Loneliness may be a feasible and acceptable treatment target within psychosocial treatments.
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Solidão/psicologia , Psicoterapia/métodos , Transtornos Psicóticos/terapia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos Piloto , Transtornos Psicóticos/psicologiaRESUMO
A subdural haematoma (SDH) is a frequently encountered pathology seen on an emergency room computed tomography (CT) head scan. An extra-axial crescentic density along the convexity of the brain or within the interhemispheric fissure is generally thought to represent a SDH; however, SDH mimics are known to occur in nature, and can be broadly classified under the subcategories of normal anatomy, artefacts, tumour, inflammation, infection, ischaemia, trauma, and iatrogenic. Understanding the typical characteristics of a SDH, knowledge of normal anatomy, close inspection of the morphology of the subdural process, changes to the adjacent structures, and rigorous attention to clinical details may reveal subtle clues that distinguish a true SDH from a mimic. This is crucial in appropriately directing clinical management. This review amalgamates most of the rare subdural processes that have been reported to mimic SDH, and discusses the imaging and clinical features that help to differentiate between them. This topic is highly valuable for radiology trainees, general radiologists, and emergency room physicians, and may serve as a refresher for the practising neuroradiologist.
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Hematoma Subdural/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , HumanosRESUMO
Haemoglobin expression is not restricted to erythroid cells. We investigated the gene expression of the haemoglobin subunits haemoglobin, alpha adult chain 1 (Hba-a1) and haemoglobin, beta (Hbb), 2,3-bisphosphoglycerate mutase (Bpgm) and the oxygen-regulated genes BCL2/adenovirus E1B interacting protein 3 (Bnip3), solute carrier family 2 (facilitated glucose transporter), member 1 (Slc2a1) and N-myc downstream regulated gene 1 (Ndrg1) in the murine preimplantation embryo, comparing invivo to invitro gene expression. Relatively high levels of Hba-a1 and Hbb were expressed invivo from the 2-cell to blastocyst stage; in contrast, little or no expression occurred invitro. We hypothesised that the presence of haemoglobin invivo creates a low oxygen environment to induce oxygen-regulated gene expression, supported by high expression of Slc2a1 and Ndrg1 in invivo relative to invitro embryos. In addition, analysis of an invitro-derived human embryo gene expression public dataset revealed low expression of haemoglobin subunit alpha (HBA) and HBB, and high expression of BPGM. To explore whether there was a developmental stage-specific effect of haemoglobin, we added exogenous haemoglobin either up to the 4-cell stage or throughout development to the blastocyst stage, but observed no difference in blastocyst rate or the inner cell mass to trophectoderm cell ratio. We conclude that haemoglobin in the invivo preimplantation embryo raises an interesting premise of potential mechanisms for oxygen regulation, which may influence oxygen-regulated gene expression.
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Blastocisto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hemoglobinas/metabolismo , Oxigênio/metabolismo , Animais , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário , Feminino , Hemoglobinas/genética , CamundongosRESUMO
The Hong Kong Reference Framework for Hypertension Care for Adults in Primary Care Settings is updated regularly to ensure it reflects the latest medical development and best practice. In 2017, guidelines from the United States included a major change, adopting the lower blood pressure values of 130/80 mm Hg in defining hypertension, in contrast to the prevailing international consensus of 140/90 mm Hg. After thorough review of the literature and international guidelines, the Advisory Group on Hong Kong Reference Framework for Care of Diabetes and Hypertension in Primary Care Settings (Advisory Group) recommends that the definition of hypertension adopted in the Reference Framework should remain unchanged as a blood pressure of ≥140/90 mm Hg, as there is currently inadequate evidence and lack of general consensus to support such change in Hong Kong. The Advisory Group agrees on individualised treatment goals, and recommends that the initial blood pressure goal for individuals with uncomplicated hypertension should be <140/90 mm Hg; for those who can tolerate it, the goal should be ≤130/80 mm Hg. A lower blood pressure is advisable for young or overweight/obese patients, smokers, and patients with other cardiovascular risk factors.
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Fidelidade a Diretrizes , Hipertensão/terapia , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/métodos , Pressão Sanguínea , Objetivos , Hong Kong , Humanos , Hipertensão/diagnósticoRESUMO
INTRODUCTION: The prevalence of overweight and obesity is increasing at an alarming rate. It is a major factor for many other metabolic disorders. This study aimed to determine the prevalence of increase body mass index (BMI) and obesity and their associated demographic characteristics among adults in an urban area. METHODS: A retrospective study was conducted where data was extracted from the Health Status Screening Form (BSSK) at health clinics in Johor Bahru. Using the World Health Organization (WHO), criteria for obesity, BMI≥30.0 kg/m2 was specified as obese and combination of both BMI ranges for overweight (25.0-30.0kg/m2) and obesity (≥30.0kg/m2) as elevated BMI. RESULTS: The overall prevalence of elevated BMI and obesity was 54.6% and 20.1% respectively. Men had a higher prevalence of elevated BMI (57.4%) with odds of 1.28 higher (95%CI: 1.04-1.58). High prevalence of elevated BMI and obesity were seen among the Indians (elevated BMI - 60.2%, obesity - 19.4%) followed by Malays (elevated BMI -57.8%, obesity - 23.1%) and Chinese showed the lowest (elevated BMI - 39.0%, obesity - 8.8%). The odds of elevated BMI and obesity were lower among younger adults as compared to older adults (≥30 years old). CONCLUSION: Using WHO criteria, about one in two adults had elevated BMI while one in five were obese. Elevated BMI and obesity disparities were evident in age and ethnicity, but sex differences were encountered in elevated BMI group.
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Obesidade/epidemiologia , Sobrepeso/epidemiologia , População Urbana/estatística & dados numéricos , Adulto , Índice de Massa Corporal , Escolaridade , Feminino , Humanos , Malásia/epidemiologia , Masculino , Estado Civil , Pessoa de Meia-Idade , Obesidade/etiologia , Sobrepeso/etiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Background: Inverted sinonasal (Schneiderian) papilloma (ISP) is a locally aggressive neoplasm often associated with sinonasal squamous cell carcinoma (SNSCC). While the etiology of ISP is not well understood, human papillomavirus (HPV) has been detected in a subset of cases. Our group recently identified activating somatic EGFR mutations in the majority of ISP and ISP-associated SNSCC. However, the relationship between EGFR mutations and HPV infection has not been explored. Patients and methods: We evaluated 58 ISP and 22 ISP-associated SNSCC (including 13 patients with matched ISP/SNSCC samples), as well as 14 SNSCC without clinical or pathologic evidence of an associated ISP. Formalin-fixed, paraffin-embedded samples were evaluated for EGFR mutations using Sanger sequencing and for HPV infection using GP5+/GP6+ PCR. HPV subtyping based on the L1 sequence was done for HPV positive cases including temporally distinct tumors for four patients. Clinicopathologic data including progression free survival was also analyzed. Results: All ISP and ISP-associated SNSCC demonstrated either an EGFR mutation or HPV infection. HPV and EGFR mutation were mutually exclusive in all cases of ISP-associated SNSCC and all but one ISP; this case was only weakly HPV positive, and analysis of a prior temporally distinct ISP specimen from this patient failed to show HPV infection, suggesting transient infection/incidental colonization. HPV subtypes in ISP and ISP-associated SNSCC were predominantly low-risk, in contrast with SNSCC without ISP association, which showed frequent high-risk HPV. All paired ISP and associated SNSCC samples demonstrated concordant HPV status and EGFR genotypes. ISP progression to SNSCC was significantly associated with the presence of HPV infection and the absence of an EGFR mutation (log-rank = 9.620, P = 0.002). Conclusions: Collectively our data show that EGFR mutations and HPV infection represent essential, alternative oncogenic mechanisms in ISP and ISP-associated SNSCC.