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Strong lines of evidence in the neuroscience literature indicate that (a) healthy sleep facilitates cognitive processing, and (b) sleep disruption is associated with cognitive dysfunction. Despite the fact that patients with pituitary disease often display both disrupted sleep and cognitive dysfunction, few previous studies investigate whether these clinical characteristics in these patients might be related. Hence, we explored whether sleep disruption in patients with pituitary disease mediates their cognitive dysfunction. We recruited 18 patients with non-functioning pituitary adenomas (NFPA) and 19 sociodemographically matched healthy controls. They completed the Global Sleep Assessment Questionnaire (thus providing self-report data regarding sleep disruption) and were administered the Brief Test of Adult Cognition by Telephone, which assesses cognitive functioning in the domains of processing speed, working memory, episodic memory, inhibition, and reasoning. We found no significant differences in cognition between patients and controls. Furthermore, spectra of sleep disturbance did not differ significantly between patients and controls. Our data suggest that NFPA patients' cognition and sleep quality is relatively intact, and that sleep disruption does not mediate cognitive dysfunction. Larger studies should characterize sleep and cognition in patients with NFPA (and other pituitary diseases) to confirm whether disruption of the former mediates impairment in the latter.
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Transtornos Cognitivos , Neoplasias Hipofisárias , Adulto , Humanos , Neoplasias Hipofisárias/complicações , África do Sul/epidemiologia , Transtornos Cognitivos/psicologia , Cognição , Sono , Testes NeuropsicológicosRESUMO
BACKGROUND: The PubMed archive contains more than 34 million articles; consequently, it is becoming increasingly difficult for a biomedical researcher to keep up-to-date with different knowledge domains. Computationally efficient and interpretable tools are needed to help researchers find and understand associations between biomedical concepts. The goal of literature-based discovery (LBD) is to connect concepts in isolated literature domains that would normally go undiscovered. This usually takes the form of an A-B-C relationship, where A and C terms are linked through a B term intermediate. Here we describe Serial KinderMiner (SKiM), an LBD algorithm for finding statistically significant links between an A term and one or more C terms through some B term intermediate(s). The development of SKiM is motivated by the observation that there are only a few LBD tools that provide a functional web interface, and that the available tools are limited in one or more of the following ways: (1) they identify a relationship but not the type of relationship, (2) they do not allow the user to provide their own lists of B or C terms, hindering flexibility, (3) they do not allow for querying thousands of C terms (which is crucial if, for instance, the user wants to query connections between a disease and the thousands of available drugs), or (4) they are specific for a particular biomedical domain (such as cancer). We provide an open-source tool and web interface that improves on all of these issues. RESULTS: We demonstrate SKiM's ability to discover useful A-B-C linkages in three control experiments: classic LBD discoveries, drug repurposing, and finding associations related to cancer. Furthermore, we supplement SKiM with a knowledge graph built with transformer machine-learning models to aid in interpreting the relationships between terms found by SKiM. Finally, we provide a simple and intuitive open-source web interface ( https://skim.morgridge.org ) with comprehensive lists of drugs, diseases, phenotypes, and symptoms so that anyone can easily perform SKiM searches. CONCLUSIONS: SKiM is a simple algorithm that can perform LBD searches to discover relationships between arbitrary user-defined concepts. SKiM is generalized for any domain, can perform searches with many thousands of C term concepts, and moves beyond the simple identification of an existence of a relationship; many relationships are given relationship type labels from our knowledge graph.
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Algoritmos , Neoplasias , Humanos , PubMed , Conhecimento , Descoberta do ConhecimentoRESUMO
Background: The PubMed database contains more than 34 million articles; consequently, it is becoming increasingly difficult for a biomedical researcher to keep up-to-date with different knowledge domains. Computationally efficient and interpretable tools are needed to help researchers find and understand associations between biomedical concepts. The goal of literature-based discovery (LBD) is to connect concepts in isolated literature domains that would normally go undiscovered. This usually takes the form of an A-B-C relationship, where A and C terms are linked through a B term intermediate. Here we describe Serial KinderMiner (SKiM), an LBD algorithm for finding statistically significant links between an A term and one or more C terms through some B term intermediate(s). The development of SKiM is motivated by the the observation that there are only a few LBD tools that provide a functional web interface, and that the available tools are limited in one or more of the following ways: 1) they identify a relationship but not the type of relationship, 2) they do not allow the user to provide their own lists of B or C terms, hindering flexibility, 3) they do not allow for querying thousands of C terms (which is crucial if, for instance, the user wants to query connections between a disease and the thousands of available drugs), or 4) they are specific for a particular biomedical domain (such as cancer). We provide an open-source tool and web interface that improves on all of these issues. Results: We demonstrate SKiM's ability to discover useful A-B-C linkages in three control experiments: classic LBD discoveries, drug repurposing, and finding associations related to cancer. Furthermore, we supplement SKiM with a knowledge graph built with transformer machine-learning models to aid in interpreting the relationships between terms found by SKiM. Finally, we provide a simple and intuitive open-source web interface ( https://skim.morgridge.org ) with comprehensive lists of drugs, diseases, phenotypes, and symptoms so that anyone can easily perform SKiM searches. Conclusions: SKiM is a simple algorithm that can perform LBD searches to discover relationships between arbitrary user-defined concepts. SKiM is generalized for any domain, can perform searches with many thousands of C term concepts, and moves beyond the simple identification of an existence of a relationship; many relationships are given relationship type labels from our knowledge graph.
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Pulmonary tuberculosis is an inflammatory disease associated with an elevated cortisol/cortisone ratio at the site of infection and an array of cytokine changes. Tuberculous pericarditis is a less common but more lethal form of tuberculosis and has a similar inflammatory process in the pericardium. As the pericardium is largely inaccessible, the effect of tuberculous pericarditis on pericardial glucocorticoids is largely unknown. We wished to describe pericardial cortisolcortisone ratio in relation to plasma and saliva cortisol/cortisone ratios and the associated changes in cytokine concentrations. The median (interquartile range) of plasma, pericardial, and saliva cortisol concentration was 443 (379-532), 303 (257-384), and 20 (10-32) nmol/L, respectively, whereas the median (interquartile range) of plasma, pericardial, and saliva cortisone concentrations was 49 (35-57), 15.0 (0.0-21.7), and 37 (25-55) nmol/L, respectively. The cortisol/cortisone ratio was highest in pericardium with median (interquartile range) of 20 (13-445), followed by plasma of 9.1 (7.4-12.1) and saliva of 0.4 (0.3-0.8). The elevated cortisol/cortisone ratio was associated with elevated pericardial, interferon gamma, tumor necrosis factor-alpha, interleukin-6, interleukin-8, and induced protein 10. Administration of a single dose of 120 mg of prednisolone was associated with the suppression of pericardial cortisol and cortisone within 24 h of administration. The cortisol/cortisone ratio was highest at the site of infection, in this case, the pericardium. The elevated ratio was associated with a differential cytokine response. The observed pericardial cortisol suppression suggests that 120 mg of prednisolone was sufficient to evoke an immunomodulatory effect in the pericardium.
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Cortisona , Pericardite Tuberculosa , Humanos , Pericardite Tuberculosa/tratamento farmacológico , Hidrocortisona , Pericárdio , Citocinas , Prednisolona/uso terapêuticoRESUMO
OBJECTIVE: To explore the experiences and care preferences of women with chronic pelvic pain, with or without a history of sexual trauma, seeking gynaecological care. DESIGN: Qualitative study. SETTING: Ambulatory endometriosis centre. POPULATION OR SAMPLE: Women aged 18-55 years with chronic pelvic pain. METHODS: Baseline demographics and sexual trauma history were obtained, and participants were assigned to focus groups according to a positive (four groups, 13 participants) or negative (two groups, nine participants) screen for a history of sexual trauma. The focus groups were led by a clinical psychologist and a gynaecological surgeon and consisted of semi-structured interviews. The interviews were audio-recorded and transcribed, and the transcripts were coded in NVivo 12. MAIN OUTCOME MEASURES: Content analysis was used to derive themes according to the participants' own words. RESULTS: Participants with chronic pelvic pain, with or without a history of sexual trauma, experienced delay in diagnosis and repetitive dismissals by clinicians. Participants' experiences of dismissals included: clinicians not listening, insufficient allocation of time to appointments and perceived redundant medical testing (i.e. sexually transmitted infection testing, urine cultures, ultrasounds). Participants identified clinician interactions as pivotal in coping with both pelvic pain and sexual abuse. Participants also provided feedback regarding trauma-informed practices and care delivery specific to patients with chronic pelvic pain. CONCLUSION: Patients with chronic pelvic pain, with or without a history of sexual trauma, report negative experiences when interacting with the healthcare system. They have clear needs and preferences regarding gynaecological care and provide feasible suggestions for improving care delivery.
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Dor Crônica , Endometriose , Delitos Sexuais , Feminino , Humanos , Dor Pélvica/terapia , Dor Crônica/terapia , Atenção à SaúdeRESUMO
BACKGROUND: Tumor-induced osteomalacia is a rare, acquired paraneoplastic syndrome, including hypophosphatemia, high serum alkaline phosphatase, reduced active vitamin D, suboptimal bone mineral density, bone pain, fragility fractures, and muscle weakness. CASE PRESENTATION: We report a case of 74-year-old male of mixed ancestry with hypophosphatemia resistant to treatment despite optimal compliance, associated with profound reduction of bone mineral density and multiple nontraumatic fractures, including bilateral rib fractures, lower-thoracic (T11, T12) vertebrae, and two fractures involving the surgical and anatomical neck of the right humerus. We discuss an approach to identifying the underlying cause of hypophosphatemia associated with fragility fractures, and options for management of this rare condition. CONCLUSION: Although rare, tumor-induced osteomalacia can be diagnosed if a logical stepwise approach is implemented. Surgery could be curative if the tumor is properly located and is resectable.
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Hipofosfatemia , Neoplasias de Tecido Conjuntivo , Osteomalacia , Síndromes Paraneoplásicas , Idoso , Fatores de Crescimento de Fibroblastos , Humanos , Hipofosfatemia/etiologia , Masculino , Neoplasias de Tecido Conjuntivo/complicações , Neoplasias de Tecido Conjuntivo/diagnóstico por imagem , Neoplasias de Tecido Conjuntivo/cirurgia , Osteomalacia/diagnóstico por imagem , Osteomalacia/etiologia , Síndromes Paraneoplásicas/etiologiaRESUMO
BACKGROUND: Insulinomas are rare clinical entities, but concurrent diabetes mellitus is even more uncommon, and the combination is easily missed. Recurrent hypoglycemia could be misconstrued as improved glycemic control. We present an unusual patient with type 2 diabetes and neuroglycopenia, with apparent improved glycemic control due to an insulinoma. CASE PRESENTATION: A 54-year-old mixed ancestry man with a positive family history of type 2 diabetes mellitus was diagnosed with type 2 diabetes mellitus and hypertension 8 years prior to admission. He presented with episodes of abnormal behavior and hypoglycemia. Inappropriately high insulin and C-peptide concentrations were identified at the time of hypoglycemia. Despite poor adherence to his diabetic treatment, he had no target organ damage relating to diabetes, and his hemoglobin A1c (HbA1c) was 5.3%. A diagnosis of insulinoma was made, and he was started on diazoxide, with endoscopic ultrasound revealing a possible lesion in the pancreatic tail measuring 12 mm × 12 mm. A fine-needle aspiration biopsy could not be performed due to overlying splenic arteries and the risk of vascular perforation. An intraoperative ultrasound confirmed a 15 mm × 10 mm tumor in the pancreatic tail, necessitating a partial pancreatectomy and splenectomy, which were curative. A well-differentiated intermediate grade 2 pancreatic neuroendocrine tumor producing insulin was confirmed on histopathology. CONCLUSIONS: Recurrent, progressive hypoglycemia and improved glycemic control in a diabetic, without an alternative explanation, may suggest an insulinoma. Insulinomas that exist with type 1 diabetes mellitus, particularly malignant insulinomas, must have escaped autoimmune attack through lack of autoantigen expression. Computed tomography on its own may be insufficiently sensitive for diagnosis of insulinomas, whereas endoscopic and intraoperative ultrasonography may improve the identification of the culprit lesion.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Insulinoma , Neoplasias Pancreáticas , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipoglicemia/etiologia , Insulinoma/cirurgia , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgiaRESUMO
OBJECTIVE: We wished to determine the prevalence, etiology, presentation, and available management strategies for primary adrenal insufficiency (PAI) in South Africa (SA), hypothesizing a prevalence greater than the described 3.1 per million. There is great inequity in healthcare allocation, as two parallel healthcare systems exist, potentially modifying PAI patients' clinical profiles, private being better resourced than public healthcare. METHODS: An online survey of physicians' experience relating to PAI. RESULTS: The physicians were managing 811 patients, equal to a prevalence of 14.2 per million. Likely causes of PAI in public/ academic vs private settings included: AIDS-related [304 (44.8%) vs 5 (3.8%); p<0.001], tuberculosis [288 (42.5%) vs 8 (6.0%); p<0.001], autoimmune disease [50 (7.4%) vs 88 (66.2%); p<0.001], malignancy [27 (4.0%) vs 7 (5.3%); p = 0.500], genetic including adrenoleukodystrophy (ALD) [5 (0.7%) vs 16 (12.0%); p<0.001], respectively. Overall, more patients presented with nausea [101 (74.3%) and vomiting 89 (65.9%), than diarrhoea 76 (58.9%); p = 0.008 and 126 (15.5%) in adrenal crisis. Features suggestive of a crisis were hypoglycaemia [40 (78.4%) vs 42 (48.8%); p = 0.001], shock [36 (67.9%) vs 31(36.9%); p<0.001], and loss of consciousness [25 (52.1%) vs 27 (32.9%); p = 0.031]. Greater unavailability of antibody testing in the public vs. the private sector [32 (66.7%) vs 30 (32.1%); p = 0.001], [serum-ACTH 25 (52.1%) vs 16 (19.5%); p<0.001] and glucocorticoids were [26 (54.2%) vs 33 (40.2%); p = 0.015]. Many patients, 389(66.7%) were not using identification, indicating that they need steroids in an emergency. CONCLUSION: A survey of South African physicians suggests a higher prevalence than previously reported. Patients presented with typical symptoms, and 15.5% presented in adrenal crisis. Significant disparities in the availability of physicians' expertise, diagnostic resources, and management options were noted in the public versus private settings. Greater awareness among health practitioners to timeously diagnose PAI is required to prevent a life-threatening outcome.
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Insuficiência Adrenal/epidemiologia , Doenças Transmissíveis/epidemiologia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Adolescente , Insuficiência Adrenal/etiologia , Adulto , Criança , Pré-Escolar , Doenças Transmissíveis/complicações , Estudos Transversais , Gerenciamento Clínico , Feminino , Instalações de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Setor Privado/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Fatores de Risco , África do Sul/epidemiologia , Adulto JovemRESUMO
Sonolysis has been proposed as a promising treatment technology to remove per- and polyfluoroalkyl substances (PFASs) from contaminated water. The mechanism of degradation is generally accepted to be high temperature pyrolysis at the bubble surface with dependency upon surface reaction site availability. However, the parametric effects of the ultrasonic system on PFAS degradation are poorly understood, making upscale challenging and leading to less than optimal use of ultrasonic energy. Hence, a thorough understanding of these parametric effects could lead to improved efficiency and commercial viability. Here, reactor characterisation was performed at 44, 400, 500, and 1000 kHz using potassium iodide (KI) dosimetry, sonochemiluminescence (SCL), and sonoluminescence (SL) in water and a solution of potassium salt of PFOS (hereafter, K-PFOS). Then the degradation of K-PFOS (10 mg L-1 in 200 mL solution) was investigated at these four frequencies. At 44 kHz, no PFOS degradation was observed. At 400, 500, and 1000 kHz the amount of degradation was 96.9, 93.8, and 91.2%, respectively, over four hours and was accompanied by stoichiometric fluoride release, indicating mineralisation of the PFOS molecule. Close correlation of PFOS degradation trends with KI dosimetry and SCL intensity was observed, which suggested degradation occurred under similar conditions to these sonochemical processes. At 1000 kHz, where the overall intensity of collapse was significantly reduced (measured by SL), PFOS degradation was not similarly decreased. Discussion is presented that suggests a hydrated electron degradation mechanism for PFOS may occur in ultrasonic conditions. This mechanism is a novel hypothesis in the field of PFAS sonolysis.
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BACKGROUND: The burden and management of primary adrenal insufficiency (PAI) in Africa have not been well documented. We aimed to identify specific disease characteristics, patient demographics, and patterns of clinical management in established PAI in Africa. METHODS: An online survey of physicians' experience relating to PAI. RESULTS: There were 1334 responses received, 589 were complete, and 332 respondents reported managing patients with hypoadrenalism. The described responses were related to a calculated pool of 5787 patients with hypoadrenalism (2746 females, 3041 males), of whom 2302 had PAI. The likely causes of PAI in Sub-Saharan Africa (SSA) vs the Middle East and North Africa (MENA) regions included autoimmune disease (20% vs 60.3%; P < 0.001), tuberculosis (34% vs 4.1%; P < 0.001), AIDS (29.8% vs 1%; P < 0.001), malignancy, and genetic conditions. Sixteen percent of AD patients (376/2302) presented in an adrenal crisis. Medical emergency identification was not used by 1233 (83.6%) SSA vs 330 (40.4%) MENA patients (P < 0.001), respectively. Relative non-availability of diagnostic tests across both regions included adrenal antibodies 63% vs 69.6% (P = 0.328), s-cortisol 49.4 % vs 26.7% (P = 0.004), s-ACTH 55.7% vs 53.3% (P = 0.217), and adrenal CT scans 52.4% vs 31.8% (P = 0.017) in the SSA and MENA region, respectively. Across the entire cohort, the overall hydrocortisone use and extrapolated proportion of synacthen use were 59.4% and 50.7%, respectively. CONCLUSIONS: Through the perception and practice of healthcare professionals, we identified significant challenges in the diagnosis and management of PAI which may herald high mortality. Differences between regions may reflect the allocation of healthcare resources.
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OBJECTIVE: To summarize the characteristics of and therapeutic options for cancer patients whose treatments may be vasotoxic and cause intracranial arterial stenotic disease and stroke. METHODS: We describe 3 patients with symptomatic cerebrovascular pathology that were being actively treated for cancer. RESULTS: Two of the patients were being treated with tyrosine kinase inhibitors (TKIs); and the third was being treated with 2 monoclonal antibodies, one of which was targeting an endothelial growth factor. These agents have been associated with vascular adverse events. Surgical revascularization was done in the first 2 patients, as they were suffering from cerebral ischemia. The third patient had suffered a significant brain hemorrhage, and therapeutic options were limited. In the first 2 patients, treatments also included antiplatelet agents and stopping/changing the TKI. In one of these patients we demonstrated regression of arterial stenosis after changing the TKI. CONCLUSIONS: Possibilities for treatment in this population, beyond the usual medical and surgical administrations, may include stopping or changing cancer drugs that may be related to the development of arterial pathology. Collaboration with oncologists is essential in this subset of patients. While aware of the potential for vascular toxicity, oncologists are often not fully appreciative of the fact that their therapeutic agents can cause stroke.
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Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Arteriopatias Oclusivas/terapia , Doenças Arteriais Cerebrais/terapia , Artérias Cerebrais/cirurgia , Revascularização Cerebral/métodos , Inibidores de Proteínas Quinases/efeitos adversos , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/induzido quimicamente , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Angiografia Cerebral/métodos , Doenças Arteriais Cerebrais/induzido quimicamente , Doenças Arteriais Cerebrais/diagnóstico por imagem , Doenças Arteriais Cerebrais/fisiopatologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Tratamento Conservador , Constrição Patológica , Substituição de Medicamentos , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Endovascular treatment of carotid cavernous fistulas (CCFs) via a transvenous approach is standard, but in rare cases this approach is challenging due to absence or thrombosis of the commonly used venous routes. A 61-year-old woman presented with a symptomatic CCF with all but one of the venous access routes to the CCF thrombosed, leaving an engorged superficial middle cerebral vein (SMCV) as the only venous outflow from the cavernous sinus. Access to the CCF was made possible after careful navigation of the sigmoid sinus, the vein of Labbé and the SMCV, bypassing the need for surgical access to the SMCV or for a direct transorbital puncture. The CCF was completely occluded by coiling and Onyx embolization. The patient made an uneventful recovery, with resolution of her symptoms. To the best of our knowledge, this access route has not been previously reported in the treatment of CCFs.
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Fístula Carótido-Cavernosa/diagnóstico por imagem , Fístula Carótido-Cavernosa/terapia , Veias Cerebrais/diagnóstico por imagem , Embolização Terapêutica/métodos , Seio Cavernoso/diagnóstico por imagem , Angiografia Cerebral/métodos , Feminino , Humanos , Pessoa de Meia-Idade , PunçõesRESUMO
Context: Patients with Addison's disease (AD) have increased cardiovascular mortality. Objective: To study visceral fat and conventional and exploratory cardiovascular risk factors in patients with AD. Design: A cross-sectional, single-center, case-control study. Subjects: Patients (n = 76; n = 51 women) with AD and 76 healthy control subjects were matched for sex, age, body mass index (BMI), and smoking habits. Main outcome measures: The primary outcome variable was visceral abdominal adipose tissue (VAT) measured using computed tomography. Secondary outcome variables were prevalence of metabolic syndrome (MetS) and 92 biomarkers of cardiovascular disease. Results: The mean ± standard deviation age of all subjects was 53 ± 14 years; mean BMI, 25 ± 4 kg/m2; and mean duration of AD, 17 ± 12 years. The median (range) daily hydrocortisone dose was 30 mg (10 to 50 mg). Median (interquartile range) 24-hour urinary free cortisol excretion was increased in patients vs controls [359 nmol (193 to 601 nmol) vs 175 nmol (140 to 244 nmol); P < 0.001]. VAT did not differ between groups. After correction for multiple testing, 17 of the 92 studied biomarkers differed significantly between patients and control subjects. Inflammatory, proinflammatory, and proatherogenic risk biomarkers were increased in patients [fold change (FC), >1] and vasodilatory protective marker was decreased (FC, <1). Twenty-six patients (34%) vs 12 control subjects (16%) fulfilled the criteria for MetS (P = 0.01). Conclusion: Despite higher cortisol exposure, VAT was not increased in patients with AD. The prevalence of MetS was increased and several biomarkers of cardiovascular disease were adversely affected in patients with AD.
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Doença de Addison/complicações , Doença de Addison/diagnóstico , Biomarcadores/análise , Doenças Cardiovasculares/diagnóstico , Gordura Intra-Abdominal/patologia , Doença de Addison/metabolismo , Doença de Addison/patologia , Adulto , Idoso , Biomarcadores/metabolismo , Doenças Cardiovasculares/complicações , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Danger signals activate Toll-like receptors (TLRs), thereby initiating inflammatory responses. Canonical TLR signalling, via Toll/Interleukin-1 receptor domain (TIR)-containing adaptors and proinflammatory transcription factors such as NF-κB, occurs in many cell types; however, additional mechanisms are required for specificity of inflammatory responses in innate immune cells. Here we show that SCIMP, an immune-restricted, transmembrane adaptor protein (TRAP), promotes selective proinflammatory cytokine responses by direct modulation of TLR4. SCIMP is a non-TIR-containing adaptor, binding directly to the TLR4-TIR domain in response to lipopolysaccharide. In macrophages, SCIMP is constitutively associated with the Lyn tyrosine kinase, is required for tyrosine phosphorylation of TLR4, and facilitates TLR-inducible production of the proinflammatory cytokines IL-6 and IL-12p40. Point mutations in SCIMP abrogating TLR4 binding also prevent SCIMP-mediated cytokine production. SCIMP is, therefore, an immune-specific TLR adaptor that shapes host defence and inflammation.
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Subunidade p40 da Interleucina-12/imunologia , Interleucina-6/imunologia , Macrófagos/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Subunidade p40 da Interleucina-12/genética , Interleucina-6/genética , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Domínios Proteicos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Quinases da Família src/genética , Quinases da Família src/imunologiaRESUMO
Arteriovenous fistulae of the orbit are exceedingly rare. They are high-flow vascular malformations involving a fistula from the ophthalmic artery to one of the draining ophthalmic veins. Presenting symptoms can mimic those of carotid cavernous fistulae or of ophthalmic venous varices, and include diplopia, proptosis, chemosis, decreased visual acuity, and retro-orbital pain. Very few case reports are published on the treatment of this aggressive vascular malformation, and they uniformly describe techniques involving a transvenous access for the embolization of the fistula. To the best of authors' knowledge, they report the first case of transarterial embolization of an intraorbital AVF.
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Fístula Arteriovenosa/terapia , Embolização Terapêutica/métodos , Embucrilato/farmacologia , Malformações Arteriovenosas Intracranianas/terapia , Artéria Oftálmica/anormalidades , Órbita/irrigação sanguínea , Idoso , Fístula Arteriovenosa/diagnóstico , Angiografia Cerebral , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Angiografia por Ressonância Magnética , Artéria Oftálmica/diagnóstico por imagemRESUMO
In this mini review, the embryological and functional development of the adrenal glands is presented from a molecular perspective. While acknowledging that this is a highly complex series of events, the processes are described in simple and broad strokes in a single text for the reader who is interested in this field but is not an active researcher. The origin of the adrenal glands is in the mesodermal ridge as early as the fourth week of gestation. Between the eighth and ninth weeks of gestation, the adrenal glands are encapsulated and this results in the presence of a distinct organ. There have been great strides in deciphering the very complicated molecular aspects of adrenal gland development in which multiple transcription factors have been identified, directing the adrenogonadal primordium into the adrenal cortex, kidney, or bipotential gonad. Adrenocorticotrophic hormone is critical for early development of the hypothalamic-pituitary adrenal axis. Several mutations in transcription factors, responsible for normal adrenal gland development have been found to induce the familial syndrome of congenital adrenal hypoplasia or neoplasia.
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Glândulas Suprarrenais/embriologia , Doença de Addison/genética , Neoplasias das Glândulas Suprarrenais/genética , Glândulas Suprarrenais/metabolismo , Carcinoma Adrenocortical/genética , Desidroepiandrosterona/metabolismo , Feto/metabolismo , Humanos , Hidrocortisona/metabolismo , Fatores de Transcrição/genéticaRESUMO
Basal bodies and centrioles are conserved microtubule-based organelles the improper assembly of which leads to a number of diseases, including ciliopathies and cancer. Tubulin family members are conserved components of these structures that are integral to their proper formation and function. We have identified the ε-tubulin gene in Tetrahymena thermophila and detected the protein, through fluorescence of a tagged allele, to basal bodies. Immunoelectron microscopy has shown that ε-tubulin localizes primarily to the core microtubule scaffold. A complete genomic knockout of ε-tubulin has revealed that it is an essential gene required for the assembly and maintenance of the triplet microtubule blades of basal bodies. We have conducted site-directed mutagenesis of the ε-tubulin gene and shown that residues within the nucleotide-binding domain, longitudinal interacting domains, and C-terminal tail are required for proper function. A single amino acid change of Thr150, a conserved residue in the nucleotide-binding domain, to Val is a conditional mutation that results in defects in the spatial and temporal assembly of basal bodies as well as their stability. We have genetically separated functions for the domains of ε-tubulin and identified a novel role for the nucleotide-binding domain in the regulation of basal body assembly and stability.
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Corpos Basais/fisiologia , Infecções por Cilióforos/metabolismo , Tetrahymena thermophila/fisiologia , Tubulina (Proteína)/fisiologia , Corpos Basais/metabolismo , Ciclo Celular/genética , Ciclo Celular/fisiologia , Centríolos/genética , Centríolos/metabolismo , Infecções por Cilióforos/genética , Microtúbulos/genética , Microtúbulos/metabolismo , Microtúbulos/fisiologia , Tetrahymena thermophila/genética , Tetrahymena thermophila/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismoRESUMO
STUDY DESIGN: Anatomical study with magnetic resonance imaging data. OBJECTIVE: To document the distances between the major retroperitoneal vessels and the anterior lumbar disc spaces; to determine the effect of patient positioning on these relationships; and to discuss ways to deal with vascular injury. SUMMARY OF BACKGROUND DATA: It is well known that there are major vascular structures anterior to the lower lumbar spine. Vascular injury during posterior approaches, however, remains a problem. These anatomical relationships have not been determined in vivo, and there are no data on the effect of turning the patient prone, and onto bolsters. METHODS: A random sampling of 49 women and 48 men was made. All examinations were performed in magnetic resonance scanners operating at 1.5 T. Measurements were made using electronic calipers on axial T2-weighted images. Post hoc studies were done on a smaller number of patients, to determine the effect of prone positioning. RESULTS: At the L4-L5 level, 66% of the common iliac arteries in women and 49% of those in men were within 5 mm of the anterior aspect of the disc space. At L5-S1, these numbers dropped to 23% for women and 19% for men. No relationship between the age of the patient and the distance from disc space to blood vessel was found. There was little change in these measurements between the supine and prone positions. The use of bolsters to decompress the abdominal contents in the prone position did not significantly alter the disc-artery distances. Venous relationships were also documented. CONCLUSION: The lower lumbar spine is confirmed to frequently be very close to the major retroperitoneal vessels. Turning the patient prone and placing the patient on bolsters does not change this relationship. This is part of the reason why vascular injuries may occur during routine lumbar spine surgery. Spine surgeons should be able to recognize and initiate treatment of such injuries.
Assuntos
Discotomia/efeitos adversos , Artéria Ilíaca/patologia , Disco Intervertebral/patologia , Vértebras Lombares/patologia , Lesões do Sistema Vascular/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Discotomia/métodos , Feminino , Humanos , Artéria Ilíaca/lesões , Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Decúbito Ventral , Fatores de Risco , Decúbito DorsalRESUMO
PURPOSE: To prospectively determine the prevalence and clinical importance of extraspinal abnormalities in adult outpatients undergoing computed tomography (CT) of the lumbar spine. MATERIALS AND METHODS: Institutional review board approval was obtained for this prospective study. Informed consent was obtained from 400 consecutive adult outpatients (mean age, 49 years; 212 male and 188 female patients) undergoing lumbar spine CT for low back pain and/or radiculopathy. Those with known malignancy were excluded. Dedicated spinal and abdominal full-field-of-view (FOV) images for each patient were reviewed by at least one neuroradiologist and two body radiologists. Extraspinal abnormalities were classified according to the CT Colonography Reporting and Data System (C-RADS). The electronic medical record of the patients with C-RADS E3 and E4 extraspinal findings were reviewed to assess how many of these findings were previously unknown, and the patients were followed up 24-36 months after the initial CT to determine their work-up and outcome. RESULTS: Extraspinal findings were present on images in 162 (40.5%) of 400 lumbar spine CT examinations; 59 (14.8%) patients had indeterminate or clinically important findings requiring clinical correlation or further evaluation. After review of the electronic medical record, the prevalence of clinically important findings was 4.3%, comprising an early-stage renal cell carcinoma and transitional cell carcinoma, chronic lymphocytic leukemia, sarcoidosis, and 13 abdominal aortic aneurysms. Excluding anatomic variants, the full FOV was required to best visualize extraspinal abnormalities in 127 (79.4%) of 160 patients. CONCLUSION: Reviewing the full-FOV images from lumbar spine CT examinations will result in the detection of a small number of substantial extraspinal pathologic findings in addition to many benign incidental findings.