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991.
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Aims/hypothesis
Diagnosing MODY is difficult. To date, selection for molecular genetic testing for MODY has used discrete cut-offs of limited clinical characteristics with varying sensitivity and specificity. We aimed to use multiple, weighted, clinical criteria to determine an individual’s probability of having MODY, as a crucial tool for rational genetic testing. 相似文献994.
Pintado V Pazos R Jiménez-Mejías ME Rodríguez-Guardado A Gil A García-Lechuz JM Cabellos C Chaves F Domingo P Ramos A Pérez-Cecilia E Domingo D 《Medicine》2012,91(1):10-17
Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is an uncommon disease, and little is known about its epidemiology, clinical features, therapy, and outcome. We performed a multicenter retrospective study of MRSA meningitis in adults. Eighty-six adult patients were included and the following data were obtained: underlying diseases, clinical presentation, analytical and microbiologic data, response to therapy, and outcome.There were 56 men (65%) and the mean age was 51.5 years; 54 of them (63%) had severe comorbidities. There were 78 cases of postoperative meningitis and 8 of spontaneous meningitis. The infection was nosocomial in 93% (80/86) of the cases. Among the 78 patients with postoperative meningitis, the most common predisposing conditions were cerebrospinal fluid (CSF) devices (74%), neurosurgery (45%), CSF leakage (17%), and head trauma (12%). Most patients had fever (89%), altered mental status (68%), headache (40%), and meningeal signs (29%). The most common CSF findings were pleocytosis (90%), elevated protein level (77%), and hypoglycorrhachia (30%). CSF Gram stain and blood cultures were positive in 49% (32/65) and 36% (16/45) of cases, respectively. An associated MRSA infection and polymicrobial meningitis appeared in 33% (28/86) and 23% (20/86) of cases, respectively. Antimicrobial therapy was given to 84 patients. Most of them received vancomycin (92%) either as monotherapy (64%) or in combination with other antibiotics (28%), for a median of 18 days. Overall 30-day mortality was 31% (27/86). Multivariate study identified 2 independent factors associated with mortality: spontaneous meningitis (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3-195.4; p = 0.007), and coma (OR, 9.7; 95% CI, 2.2-42.3; p = 0.002).In conclusion, MRSA is a relatively uncommon but serious disease. Although most cases are nosocomial infections appearing in neurosurgical patients, spontaneous meningitis may present as a community-onset infection in patients with severe comorbidities requiring frequent contact with the health care system. Most patients have a favorable response to vancomycin, but the beneficial effect of combined and intraventricular therapy, or alternative drugs, remains unclear. MRSA meningitis is associated with a high mortality, and the presence of spontaneous infection and coma are the most important prognostic factors. 相似文献
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B Kaplan-Türköz LF Jiménez-Soto C Dian C Ertl H Remaut A Louche T Tosi R Haas L Terradot 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(36):14640-14645
Infection with the gastric pathogen Helicobacter pylori is a risk factor for the development of gastric cancer. Pathogenic strains of H. pylori carry a type IV secretion system (T4SS) responsible for the injection of the oncoprotein CagA into host cells. H. pylori and its cag-T4SS exploit α5β1 integrin as a receptor for CagA translocation. Injected CagA localizes to the inner leaflet of the host cell membrane, where it hijacks host cell signaling and induces cytoskeleton reorganization. Here we describe the crystal structure of the N-terminal ∼100-kDa subdomain of CagA at 3.6 Å that unveils a unique combination of folds. The core domain of the protein consists of an extended single-layer β-sheet stabilized by two independent helical subdomains. The core is followed by a long helix that forms a four-helix helical bundle with the C-terminal domain. Mapping of conserved regions in a set of CagA sequences identified four conserved surface-exposed patches (CSP1–4), which represent putative hot-spots for protein–protein interactions. The proximal part of the single-layer β-sheet, covering CSP4, is involved in specific binding of CagA to the β1 integrin, as determined by yeast two-hybrid and in vivo competition assays in H. pylori cell-culture infection studies. These data provide a structural basis for the first step of CagA internalization into host cells and suggest that CagA uses a previously undescribed mechanism to bind β1 integrin to mediate its own translocation. 相似文献
997.
Campbell M Ganetzky B 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(11):E648-E655
Although the complexity and circuitry of nervous systems undergo evolutionary change, we lack understanding of the general principles and specific mechanisms through which it occurs. The Drosophila larval neuromuscular junction (NMJ), which has been widely used for studies of synaptic development and function, is also an excellent system for studies of synaptic evolution because the genus spans >40 Myr of evolution and the same identified synapse can be examined across the entire phylogeny. We have now characterized morphology of the NMJ on muscle 4 (NMJ4) in >20 species of Drosophila. Although there is little variation within a species, NMJ morphology and complexity vary extensively between species. We find no significant correlation between NMJ phenotypes and phylogeny for the species examined, suggesting that drift alone cannot explain the phenotypic variation and that selection likely plays an important role. However, the nature of the selective pressure is still unclear because basic parameters of synaptic function remain uniform. Whatever the mechanism, NMJ morphology is evolving rapidly in comparison with other morphological features because NMJ phenotypes differ even between several sibling species pairs. The discovery of this unexpectedly extensive divergence in NMJ morphology among Drosophila species provides unique opportunities to investigate mechanisms that regulate synaptic growth; the interrelationships between synaptic morphology, neural function, and behavior; and the evolution of nervous systems and behavior in natural populations. 相似文献
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999.
Cardiac sarcoid is an infiltrative, granulomatous disease of the myocardium. It is more prevalent entity than once believed, especially subclinical disease. It affects heart mechanics causing ventricular failure, and disrupts the cardiac electrical system leading to third degree heart block, malignant ventricular arrhythmias, and sudden cardiac death. This makes early diagnosis and treatment of this devastating disease essential. Based on reviewed literature this paper proposes step-wise diagnostic and therapeutic algorithms for patients with suspected cardiac sarcoidoisis who do or do not have prior history of systemic sarcoidosis. 相似文献
1000.
Objectives:A personal or family history of colorectal adenomas increases the risk of colorectal cancer (CRC). We aimed to compare physicians' communication with polyp patients vs. non-polyp patients, assess whether polyps or CRC family history were associated with physician-patient communication, and describe patients' disclosure of colonoscopy and polyp diagnosis to their relatives.Methods:Four hundred nine patients completed an online survey regarding physician-patient communication of colonoscopy results, perceived personal and familial risk of polyps and CRC, and disclosure of colonoscopy results to relatives.Results:Six percent of participants reported that their physicians discussed familial risks. Polyp diagnosis and family history predicted physician-patient discussions about familial CRC risks. Polyp diagnosis predicted physician-patient discussions of future surveillance. Twenty-two percent of patients told none of their relatives that they had a colonoscopy. Family history, gender, and education were associated with patient-family communication.Conclusions:There is room for improvement in physician-patient and patient-family communication following colonoscopy. 相似文献