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1.
J Endocrinol Invest ; 47(10): 2449-2459, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38536658

RESUMO

PURPOSE: No consensus exists as the gold standard for Cushing's Syndrome (CS) screening. This study aimed to evaluate the diagnostic accuracy and utility of late-night salivary cortisol (LNSC) and cortisone (LNSE), overnight dexamethasone suppression test (ODST), and urinary free cortisol (UFC) in developing a screening algorithm for CS. METHODS: A retrospective, single-centre analysis on 93 adult patients referred to the Oxford Centre for Diabetes, Endocrinology, and Metabolism for CS evaluation (2017-2022). Data were analysed using binomial logistic regression and area under the receiver-operating curve (AUROC). RESULTS: Fifty-three patients were diagnosed with CS. LNSC (sensitivity 87.5%, specificity 64.9%, AUC 0.76), LNSE (sensitivity 72.4%, specificity 85.7%, AUC 0.79), and ODST (sensitivity 94.7%, specificity 52.1%; AUC 0.74) demonstrated comparable effectiveness for CS diagnosis. Their combined application increased diagnostic accuracy (AUC 0.91). UFC was not statistically significant. Pre-test clinical symptom inclusion improved screening test performance (AUC LNSC: 0.83; LNSE: 0.84; ODST: 0.82). For CD diagnosis, LNSE + LNSC (AUC 0.95) outperformed ODST. Combining these with ACTH levels < 12.6 pmol/L perfectly distinguished MACS (AUC 1.00). ODST (AUC 0.76) exhibited superior performance (sensitivity 100.0%, specificity 52.2%) in MACS detection. CONCLUSIONS: LNSC, LNSE, and ODST are robust tools for CS screening, with their combined use offering the highest diagnostic precision. LNSE, especially when used with LNSC, is highly effective for CD diagnosis, exceeding ODST accuracy. ODST is preferable for MACS identification. Integrating ACTH levels markedly improves differentiation between CD and MACS. Conversely, UFC shows limited diagnostic utility.


Assuntos
Algoritmos , Síndrome de Cushing , Hidrocortisona , Humanos , Síndrome de Cushing/diagnóstico , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Hidrocortisona/análise , Hidrocortisona/urina , Hidrocortisona/sangue , Centros de Atenção Terciária , Saliva/química , Saliva/metabolismo , Dexametasona , Cortisona/análise , Biomarcadores/análise
2.
BMC Med Educ ; 24(1): 43, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191382

RESUMO

BACKGROUND: Imposter Phenomenon (IP) is a subjective feeling of intellectual fraudulence and self-doubt experienced by individuals in goal-orientated high-achieving professions. The impact of IP within healthcare has been associated with individual physical and mental health and concerns around training, career progression and DEI at an institutional level. To effectively address IP in healthcare, this scoping review aims to explore educational interventions designed to empower high-achieving individuals with the tools needed to confront and overcome IP. METHODS: The scoping review adhered to a predetermined protocol informed by the JBI methodology and PRISMA-ScR guidelines in order to identify educational interventions addressing IP in high-achieving industries. Articles were searched across multiple databases, including MEDLINE (Ovid), PsychINFO, SCOPUS, and Web of Science, alongside grey literature, without imposing any time constraints. A systematic approach including a thematic analysis allowed for a nuanced exploration and interpretation of the identified educational interventions and their impact on addressing IP. RESULTS: Seventeen articles were incorporated into the review, with the majority originating from the USA and majority being published since 2020. Ten studies targeted healthcare professionals, undergraduate and postgraduate healthcare students. Majority of studies aimed at addressing IP, featured a larger number of female participants than males. Workshops with self-reflection and group-guided exercises to overcome IP were the most popular educational interventions. Coaching and structured supervision were also suggested. Across all papers, three themes emerged for coping strategies: individual, peer-to-peer, and institutional. CONCLUSIONS: This scoping review suggests how group and individual interventions such as workshops, small group discussions and coaching can be used to overcome IP in healthcare. Institutional changes like diversity promotion, supervisor education, and support networks are crucial in addressing IP. Further long term and speciality specific assessments are needed to measure impact. Overall, the review highlights how educational awareness and a variety of strategies can be implemented to create a supportive environment for professionals dealing with IP, promoting their well-being and success.


Assuntos
Transtornos de Ansiedade , Pessoal de Saúde , Autoimagem , Feminino , Humanos , Masculino , Transtornos de Ansiedade/terapia , Emoções , Estudantes de Ciências da Saúde , Psicoterapia de Grupo , Pessoal de Saúde/psicologia
3.
Clin Radiol ; 78(8): 555-564, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37217396

RESUMO

IgG4-related disease is a multisystem immune-mediated disorder associated with lesions manifesting an IgG4-rich plasma cell infiltrate and often raised serum IgG4 concentrations. The disease can mimic neoplastic, infective, and inflammatory processes due to features such as development of masses or organ enlargement. Prompt consideration of this diagnosis is essential to avoid unnecessary investigations and offer appropriate treatments, which can include steroids and other immunosuppressive agents. Although histology is typically diagnostic, imaging is critical to assess disease burden, determine biopsy targets, and evaluate response to treatment. Characteristic imaging features can also point towards the diagnosis in the absence of biopsy. This review highlights these features, as well as more atypical findings, grouped by organ or system. Differential diagnoses are emphasised. The full spectrum of imaging methods is discussed. Whole-body imaging with integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) has an evolving role in the detection of multi-organ involvement and subsequent follow-up.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imunoglobulina G
4.
J Endocrinol Invest ; 46(10): 1961-1982, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37058223

RESUMO

PURPOSE: The hypothalamic-pituitary-adrenal (HPA) axis exerts many actions on the central nervous system (CNS) aside from stress regulation. Glucocorticoids (GCs) play an important role in affecting several cognitive functions through the effects on both glucocorticoid (GR) and mineralocorticoid receptors (MR). In this review, we aim to unravel the spectrum of cognitive dysfunction secondary to derangement of circulating levels of endogenous and exogenous glucocorticoids. METHODS: All relevant human prospective and retrospective studies published up to 2022 in PubMed reporting information on HPA disorders, GCs, and cognition were included. RESULTS: Cognitive impairment is commonly found in GC-related disorders. The main brain areas affected are the hippocampus and pre-frontal cortex, with memory being the most affected domain. Disease duration, circadian rhythm disruption, circulating GCs levels, and unbalanced MR/GR activation are all risk factors for cognitive decline in these patients, albeit with conflicting data among different conditions. Lack of normalization of cognitive dysfunction after treatment is potentially attributable to GC-dependent structural brain alterations, which can persist even after long-term remission. CONCLUSION: The recognition of cognitive deficits in patients with GC-related disorders is challenging, often delayed, or mistaken. Prompt recognition and treatment of underlying disease may be important to avoid a long-lasting impact on GC-sensitive areas of the brain. However, the resolution of hormonal imbalance is not always followed by complete recovery, suggesting irreversible adverse effects on the CNS, for which there are no specific treatments. Further studies are needed to find the mechanisms involved, which may eventually be targeted for treatment strategies.


Assuntos
Glucocorticoides , Sistema Hipotálamo-Hipofisário , Humanos , Glucocorticoides/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Cognição
5.
BMC Nephrol ; 23(1): 47, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090403

RESUMO

BACKGROUND: The leading cause of death in end-stage kidney disease is related to cardiovascular disease. Macrophages are known to be involved in both chronic kidney disease (CKD) and heart failure, however their role in the development of cardiorenal syndrome is less clear. We thus sought to investigate the role of macrophages in uremic cardiac disease. METHODS: We assessed cardiac response in two experimental models of CKD and tested macrophage and chemokine implication in monocytopenic CCR2-/- and anti-CXCL10 treated mice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSC-derived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors. RESULTS: We found that reduced kidney function resulted in the expansion of cardiac macrophages, in particular through local proliferation of resident populations. Influx of circulating monocytes contributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophage expansion in uremic disease. In humans, we found increased plasma CXCL10 concentrations in advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiac fibroblasts. CONCLUSIONS: This study provides new insight into the role of the innate immune system in uremic cardiomyopathy.


Assuntos
Coração/fisiopatologia , Macrófagos , Miocárdio/patologia , Insuficiência Renal Crônica/fisiopatologia , Animais , Camundongos
6.
BMC Med Educ ; 21(1): 390, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34284771

RESUMO

BACKGROUND: Technological advances have previously been hailed as a new dawn in Higher Education, with the advent of 'massive open online courses' (MOOCs) and online learning. Virtual platforms have potential advantages such as accessibility and availability but simply transferring educational material to the online environment may not ensure high quality learning. Clinical examination is a fundamental principle of medical assessment, and this study aimed to assess the role of technology in teaching these skills. AIMS/OBJECTIVES: To determine whether three teaching modalities were of equal efficacy in teaching examination of the shoulder joint to naïve medical students. METHODS: Sixty-seven pre-clinical medical students naïve to large joint examination were recruited. Participants completed a learning style questionnaire and were then block randomised to three study: textbook study, face-to-face seminar, or video tutorial via online platform. The same examination technique was taught in all groups, with the intervention being the method of delivery All second year students were eligible for inclusion. The single exclusion criteria was previous exposure to clinical examination teaching. Students were assessed using a standardised scoring system at baseline (pre-intervention), and days 5 and 19 post-intervention (maximum score 30). Assessors were blinded to group allocation. The primary outcome was assessment score at day 5 post intervention. RESULTS: There was no difference between the three groups at baseline assessment (mean scores 2.4 for textbook, 2.8 for face-to-face, and 3.1 for video; p = 0.267). Mean post-intervention scores were 16.5 textbook, 25.5 face-to-face, and 22.4 video (p < 0.001, η2 = .449). There was no change between day 5 and day 19 post-intervention assessment scores in any group (p = 0.373), Preferred learning style did not affect scores (p = 0.543). CONCLUSION: Face-to-face teaching was the most effective method for teaching clinical examination of the shoulder. Technology can potentially increase accessibility and remove geographic barriers, but is not as effective if teaching techniques are simply mirrored in an online format. Online platforms allow in depth data analysis of how learners interact with educational material and this may have value in improving the design of online educational materials, and is a potential area for further research.


Assuntos
Articulação do Ombro , Estudantes de Medicina , Competência Clínica , Avaliação Educacional , Humanos , Exame Físico , Método Simples-Cego
7.
Anaesthesia ; 75(5): 654-663, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32017012

RESUMO

These guidelines aim to ensure that patients with adrenal insufficiency are identified and adequately supplemented with glucocorticoids during the peri-operative period. There are two major categories of adrenal insufficiency. Primary adrenal insufficiency is due to diseases of the adrenal gland (failure of the hormone-producing gland), and secondary adrenal insufficiency is due to deficient adrenocorticotropin hormone secretion by the pituitary gland, or deficient corticotropin-releasing hormone secretion by the hypothalamus (failure of the regulatory centres). Patients taking physiological replacement doses of corticosteroids for either primary or secondary adrenal insufficiency are at significant risk of adrenal crisis and must be given stress doses of hydrocortisone during the peri-operative period. Many more patients other than those with adrenal and hypothalamic-pituitary causes of adrenal failure are receiving glucocorticoids as treatment for other medical conditions. Daily doses of prednisolone of 5 mg or greater in adults and 10-15 mg.m-2 hydrocortisone equivalent or greater in children may result in hypothalamo-pituitary-adrenal axis suppression if administered for 1 month or more by oral, inhaled, intranasal, intra-articular or topical routes; this chronic administration of glucocorticoids is the most common cause of secondary adrenal suppression, sometimes referred to as tertiary adrenal insufficiency. A pragmatic approach to adrenal replacement during major stress is required; considering the evidence available, blanket recommendations would not be appropriate, and it is essential for the clinician to remember that adrenal replacement dosing following surgical stress or illness is in addition to usual steroid treatment. Patients with previously undiagnosed adrenal insufficiency sometimes present for the first time following the stress of surgery. Anaesthetists must be familiar with the symptoms and signs of acute adrenal insufficiency so that inadequate supplementation or undiagnosed adrenal insufficiency can be detected and treated promptly. Delays may prove fatal.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Glucocorticoides/uso terapêutico , Assistência Perioperatória/métodos , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/fisiopatologia , Adulto , Criança , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Guias como Assunto , Humanos , Prevalência , Resultado do Tratamento , Reino Unido
8.
Br J Surg ; 105(8): 1061-1069, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29558567

RESUMO

BACKGROUND: Recent reviews suggest that the way in which surgeons prepare for a procedure (warm up) can affect performance. Operating lists present a natural experiment to explore this phenomenon. The aim was to use a routinely collected large data set on surgical procedures to understand the relationship between case list order and operative performance. METHOD: Theatre lists involving the 35 procedures performed most frequently by senior surgeons across 38 private hospitals in the UK over 26 months were examined. A linear mixed-effects model and matched analysis were used to estimate the impact of list order and the cost of switching between procedures on a list while controlling for key prognosticators. The influence of procedure method (open versus minimally invasive) and complexity was also explored. RESULTS: The linear mixed-effects model included 255 757 procedures, and the matched analysis 48 632 pairs of procedures. Repeating the same procedure in a list resulted in an overall time saving of 0·98 per cent for each increase in list position. Switching between procedures increased the duration by an average of 6·48 per cent. The overall reduction in operating time from completing the second procedure straight after the first was 6·18 per cent. This pattern of results was consistent across procedure method and complexity. CONCLUSION: There is a robust relationship between operating list composition and surgical performance (indexed by duration of operation). An evidence-based approach to structuring a theatre list could reduce the total operating time.


Assuntos
Competência Clínica/estatística & dados numéricos , Salas Cirúrgicas/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Hospitais Privados , Humanos , Modelos Lineares , Duração da Cirurgia , Reino Unido
9.
Diabet Med ; 35(1): 89-98, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29094442

RESUMO

AIMS: To define the attitudes and current clinical practice of diabetes specialists with regard to non-alcoholic fatty liver disease and, based on the results, implement an evidenced-based pathway for non-alcoholic fatty liver disease assessment. METHODS: An online survey was disseminated to diabetes specialists. Based on findings from this survey, we sought a local solution by launching an awareness campaign and implementing a screening algorithm across all diabetes clinics at a secondary/tertiary referral centre. RESULTS: A total of 133 diabetes specialists responded to the survey. Fewer than 5% of responders correctly assessed the prevalence and severity of advanced fibrotic non-alcoholic fatty liver disease in people with diabetes as 50-75%. Whilst most clinicians performed liver function tests, only 5.7% responded stating that they would use, or had used, a non-invasive algorithm to stage the severity of non-alcoholic fatty liver disease. Implementing a local non-alcoholic fatty liver disease awareness campaign and screening strategy using pre-printed blood request forms, we ensured that 100% (n=395) of all people with Type 1 and Type 2 diabetes mellitus attending secondary/tertiary care diabetes clinics over a 6-month period were appropriately screened for advanced fibrotic non-alcoholic fatty liver disease using the Fib-4 index; 17.9% required further investigation or assessment. CONCLUSIONS: The prevalence and severity of non-alcoholic fatty liver disease are underestimated among diabetes specialists. The Fib-4 index can easily be incorporated into clinical practice in secondary/tertiary care to identify those individuals at risk of advanced fibrosis who require further assessment and who may benefit from a dedicated multidisciplinary approach to their management.


Assuntos
Competência Clínica , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Padrões de Prática Médica , Adulto , Idoso , Algoritmos , Atitude do Pessoal de Saúde , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Gerenciamento Clínico , Feminino , Hospitais Universitários , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Índice de Gravidade de Doença , Inquéritos e Questionários , Reino Unido
10.
Br J Dermatol ; 178(2): 535-540, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28714061

RESUMO

BACKGROUND: Hair and scalp problems are common. Unfortunately, many uncertainties exist around the most effective management and treatment strategies for these disorders. OBJECTIVES: To identify uncertainties in hair-loss management, prevention, diagnosis and treatment that are important to both people with hair loss and healthcare professionals. METHODS: A Hair Loss Priority Setting Partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in hair loss. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants; following exclusions 884 uncertainties relating to hair loss (excluding alopecia areata) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that was taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for hair loss (excluding alopecia areata) to guide researchers and funding bodies to support studies important to both patients and clinicians.


Assuntos
Alopecia/terapia , Pesquisa , Alopecia/diagnóstico , Alopecia/prevenção & controle , Consenso , Dermatologia/organização & administração , Pessoal de Saúde , Humanos , Relações Interprofissionais , Inquéritos e Questionários
11.
Br J Dermatol ; 176(5): 1316-1320, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27696375

RESUMO

BACKGROUND: Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.


Assuntos
Alopecia em Áreas/terapia , Pesquisa , Cuidadores , Prioridades em Saúde , Inquéritos Epidemiológicos , Humanos , Relações Médico-Paciente , Relações Profissional-Família
12.
Br J Cancer ; 114(12): 1367-75, 2016 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-27300108

RESUMO

BACKGROUND: Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation. METHODS: Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC. RESULTS: We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ⩾3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001). CONCLUSION: CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.


Assuntos
Carcinoma Ductal Pancreático/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias Pancreáticas/patologia , Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Estudos de Coortes , Humanos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/sangue , Proteínas Proto-Oncogênicas p21(ras)/genética
13.
Clin Endocrinol (Oxf) ; 85(6): 881-890, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27374760

RESUMO

BACKGROUND & OBJECTIVES: Postnatal depression correlates with postpartum weight retention, and dysregulated cortisol metabolism is evident in depressed individuals. Cortisol metabolism, BMI and metabolic phenotype are robustly associated, but the role of cortisol metabolism in postnatal mental health and weight loss has never been examined. DESIGN: A longitudinal observation. PATIENTS: Forty nine healthy women with uncomplicated pregnancy. MEASUREMENTS: BMI and urinary steroid metabolites at 1 week and 1, 3, 6 and 12 months postpartum. Validated urinary steroid metabolite ratios were measured to determine the activities of 11ß-hydroxysteroid dehydrogenases (11ß-HSD) that interconvert inactive cortisone and active cortisol and the 5α-reductases that clear cortisol to its inactive metabolites. Postnatal depression symptoms were measured at 1, 6 and 12 months. RESULTS: Low 5α-reductase activity was associated with greater weight loss across the first year, independent of demographics, breastfeeding and depression. Postpartum BMI change was unrelated to postnatal depression at any time. Symptoms of postnatal depression were related to higher cortisol metabolite production at 12 months, independent of demographics and breastfeeding. CONCLUSIONS: Greatest weight loss in the postpartum year was associated with lower conversion of cortisone to cortisol and lower conversion of cortisol to its metabolites, supporting previous work that demonstrates the facilitative role of lower 5α-reductase and 11ß-HSD-1 in weight loss. Greater depression symptoms were associated with higher cortisol metabolite production rates. Whilst weight and mental health are both associated with dysregulation of the HPA axis, there may be different pathways towards depressed and obese phenotypes in healthy postpartum samples.


Assuntos
Depressão Pós-Parto/etiologia , Hidrocortisona/metabolismo , Período Pós-Parto/metabolismo , Redução de Peso , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Adulto , Colestenona 5 alfa-Redutase/metabolismo , Cortisona/metabolismo , Feminino , Humanos , Estudos Longitudinais , Gravidez , Adulto Jovem
14.
Nitric Oxide ; 58: 59-66, 2016 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-27319282

RESUMO

BACKGROUND: Tissue hypoxia is a cardinal feature of inflammatory diseases and modulates monocyte function. Nitric oxide is a crucial component of the immune cell response. This study explored the metabolism of the endogenous inhibitor of nitric oxide production asymmetric dimethylarginine(ADMA) by monocyte dimethylarginine dimethylaminohydrolase 2(DDAH2), and the role of this pathway in the regulation of the cellular response and the local environment during hypoxia. METHODS: Peritoneal macrophages were isolated from a macrophage-specific DDAH2 knockout mouse that we developed and compared with appropriate controls. Cells were exposed to 3% oxygen followed by reoxygenation at 21%. Healthy volunteers underwent an 8 h exposure to normobaric hypoxia with an inspired oxygen percentage of 12%. Peripheral blood mononuclear cells were isolated from blood samples taken before and at the end of this exposure. RESULTS: Intracellular nitrate plus nitrite(NOx) concentration was higher in wild-type murine monocytes after hypoxia and reoxygenation than in normoxia-treated cells (mean(SD) 13·2(2·4) vs 8·1(1·7) pmols/mg protein, p = 0·009). DDAH2 protein was 4·5-fold (SD 1·3) higher than in control cells (p = 0·03). This increase led to a 24% reduction in ADMA concentration, 0·33(0.04) pmols/mg to 0·24(0·03), p = 0·002). DDAH2-deficient murine monocytes demonstrated no increase in nitric oxide production after hypoxic challenge. These findings were recapitulated in a human observational study. Mean plasma NOx concentration was elevated after hypoxic exposure (3·6(1.8)µM vs 6·4(3·2), p = 0·01), which was associated with a reduction in intracellular ADMA in paired samples from 3·6(0.27) pmols/mg protein to 3·15(0·3) (p < 0·01). This finding was associated with a 1·9-fold(0·6) increase in DDAH2 expression over baseline(p = 0·03). DISCUSSION: This study shows that in both human and murine models of acute hypoxia, increased DDAH2 expression mediates a reduction in intracellular ADMA concentration which in turn leads to elevated nitric oxide concentrations both within the cell and in the local environment. Cells deficient in DDAH2 were unable to mount this response.


Assuntos
Amidoidrolases/metabolismo , Hipóxia/metabolismo , Monócitos/fisiologia , Óxido Nítrico/biossíntese , Adolescente , Adulto , Amidoidrolases/genética , Animais , Arginina/análogos & derivados , Arginina/sangue , Hipóxia Celular , Humanos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Nitratos/sangue , Nitritos/sangue , Adulto Jovem
15.
Phys Rev Lett ; 115(5): 052702, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26274415

RESUMO

26Al is an important radioisotope in astrophysics that provides evidence of ongoing nucleosynthesis in the Galaxy. The 23Na(α, p)26Mg reaction has been identified by a sensitivity study as being one of the most important reactions for the production of 26Al in the convective C/Ne burning shell of massive stars. Owing to large uncertainties in previous experimental data, model calculations are used for the reaction rate of 23Na(α, p)26Mg in this sensitivity study. Current experimental data suggest a reaction rate a factor of ∼40 higher than model calculations. However, a new measurement of this reaction cross section has been made in inverse kinematics in the energy range E(c.m.)=1.28-3.15 MeV at TRIUMF, and found to be in reasonable agreement with the model calculation. A new reaction rate is calculated and tight constraints on the uncertainty in the production of 26Al, due to this reaction, are determined.

17.
Diabetes Obes Metab ; 16(7): 651-60, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24962805

RESUMO

BACKGROUND: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. METHODS: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. RESULTS: Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. CONCLUSION: NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH.


Assuntos
Glicerol/metabolismo , Resistência à Insulina , Lipólise , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adipocinas/sangue , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Gluconeogênese , Glucose/metabolismo , Técnica Clamp de Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Inflamação/metabolismo , Insulina/administração & dosagem , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo
18.
Front Surg ; 10: 1251444, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818209

RESUMO

Background: Surgical site infections (SSI) complicate up to 40% of surgical procedures, leading to increased patient morbidity and mortality. Previous research identified disparities in SSI prevention guidelines and clinical practices across different institutions. The study aims to identify variations in SSI prevention practices within and between specialties and financial systems and provide a representation of existing SSI preventative measures to help improve the standardization of SSI prevention practices. Methods: This collaborative cross-sectional survey will be aimed at pan-surgical specialties internationally. The study has been designed and will be reported in line with the CROSS and CHERRIES standards. An international study steering committee will design and internally validate the survey in multiple consensus-based rounds. This will be based on SSI prevention measures outlined in the CDC (2017), WHO (2018), NICE (2019), Wounds UK (2020) and the International Surgical Wound Complications Advisory Panel (ISWCAP) guidelines. The questionnaire will include demographics, SSI surveillance, preoperative, peri-operative and postoperative SSI prevention. Data will be collected on participants' surgical specialty, operative grade, of practice and financial healthcare system of practice. The online survey will be designed and disseminated using QualtricsXM Platform™ through national and international surgical colleges and societies, in addition to social media and snowballing. Data collection will be open for 3 months with reminders, and raking will be used to ascertain the sample. Responses will be analyzed, and the chi-square test used to evaluate the impact of SSI prevention variables on responses. Discussion: Current SSI prevention practice in UK Vascular surgery varies considerably, with little consensus on many measures. Given the inconsistency in guidelines on how to prevent SSIs, there is a need for standardization. This survey will investigate the disparity in SSI preventative measures between different surgical fields and countries.

19.
Public Health ; 126 Suppl 1: S47-S52, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22795606

RESUMO

OBJECTIVES: Keep Well, an anticipatory care programme which commenced in Scotland in 2006, aims to reduce health inequalities through holistic health checks in primary care in deprived communities. A new, non-clinical outreach worker role was created to provide support and signposting to Keep Well patients following their health check. There is currently little evidence regarding how the role is perceived. The aim of this study was to understand how staff and patients view the Keep Well outreach worker role. STUDY DESIGN: A qualitative interview-based study was carried out between July and October 2010. METHODS: One-to-one interviews were conducted with 12 Keep Well staff and four patients. Interviews were transcribed, coded and analysed using a thematic analysis approach. RESULTS: The outreach worker role was viewed positively, particularly in terms of partnership working with practices and local services, and the benefits of support to patients. Referring patients to outreach workers reduced pressure on staff, who were able to spend more time on patients' physical health rather than mental health or lifestyle support. Support from an outreach worker enabled patients to make changes to their life and their health. Concerns were about staff turnover, poor referral rates, set-up of the project and misinterpretation of the role. CONCLUSION: Patients and staff perceive benefits from the outreach worker role in providing motivational support to patients from deprived areas.


Assuntos
Disparidades nos Níveis de Saúde , Saúde Holística , Áreas de Pobreza , Papel Profissional , Doenças Cardiovasculares/prevenção & controle , Relações Comunidade-Instituição , Feminino , Humanos , Masculino , Programas de Rastreamento , Pesquisa Qualitativa , Escócia
20.
J Mech Behav Biomed Mater ; 125: 104866, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655943

RESUMO

Accurate biomechanical properties of the human cranial dura mater are paramount for computational head models, artificial graft developments and biomechanical basic research. Yet, it is unclear whether areas of the dura containing meningeal vessels biomechanically differ from avascular areas. Here, 244 dura mater samples with or without vessels from 32 cadavers were tested in a quasi-static uniaxial tensile testing setup. The thicknesses of the meningeal and periosteal dura in vascular and avascular areas were histologically investigated in 36 samples using van Gieson staining. The elastic modulus of 112 MPa from dura samples containing vessels running transversely was significantly lower than samples with vessels running longitudinally (151 MPa; p < 0.001). The ultimate tensile strength of dura samples with transversely running vessels (11.1 MPa) was significantly lower in comparison to both avascular samples (14.9 MPa; p < 0.001) and samples with a longitudinally running vessel (15.0 MPa; p < 0.001). The maximum force of dura samples with longitudinally running vessels was 37 N (p < 0.001), this was significantly higher compared to the other groups which were 23 N (p < 0.001). The meningeal and periosteal dura layer thicknesses were not statistically different in avascular areas (p > 0.222). However, around the vessels, the meningeal dura layer was significantly thicker compared to the periosteal layer (p ≤ 0.019). The sum of the meningeal and periosteal layers was similar between vascular and avascular areas (p ≥ 0.071). Vascular areas of the human cranial dura mater withstand the same forces as avascular areas when being stretched. When stretched along the vessel, the dura-vessel composite can withstand even higher tensile forces compared to avascular areas. Vascular areas of the cranial dura mater seem to be similar when compared to avascular areas making their separate simulation in computational models non-essential.


Assuntos
Dura-Máter , Crânio , Fenômenos Biomecânicos , Biofísica , Humanos , Resistência à Tração
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