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72.
Gabriella de M. Abreu Roberta M. Tarantino Ana Carolina P. da Fonseca Ritiele B. de Souza Camila A.P.D. Soares Pedro H. Cabello Melanie Rodacki Lenita Zajdenverg Verônica M. Zembrzuski Mário Campos Junior 《European journal of medical genetics》2021,64(5):104194
Maturity-Onset Diabetes of the Young type 4 is a rare form of diabetes mellitus, caused by mutations in the PDX1 gene. However, only a few mutations in this gene have been associated as a cause of monogenic diabetes up to date. It makes difficult to create a clinical manifestation profile of this disease and, consequently, to improve the therapeutic management for these patients. Here we report a normal weight woman, diagnosed with diabetes mellitus at 27 years old, during her first pregnancy. At the time of the recruitment, she was 40 years old and had a body mass index of 23.9 kg/m2, glycated hemoglobin level of 9.6%, and fasting plasma glucose (FPG) of 254 mg/dL. She presented no diabetic complications and she was being treated with insulin. She reported a family history of diabetes mellitus characteristic of an autosomal dominant mode of inheritance. Molecular analysis of the PDX1 gene revealed the missense variant c.532G > A (p.(Glu178Lys)) segregating from the patient to her son, reported as diabetic. It was absent in her healthy daughter. The c.532G > A seems to be a rare variant, absent in human variants databases, and among 86 normoglycemic controls. Eight in silico algorithms classified this variant as probably pathogenic. Additionally, analysis of the evolutionary conservation showed the glutamic acid in the position 178 of PDX-1 protein as conserved among several species. Our findings reinforce the importance of screening rare MODY genes among families with suspicion of monogenic diabetes to help better understand the clinical manifestations of this disease. 相似文献
73.
For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19.We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research. 相似文献
74.
《Clinical microbiology and infection》2021,27(10):1422-1430
BackgroundThere are several prognostic models to estimate the risk of mortality after surgery for active infective endocarditis (IE). However, these models incorporate different predictors and their performance is uncertain.ObjectiveWe systematically reviewed and critically appraised all available prediction models of postoperative mortality in patients undergoing surgery for IE, and aggregated them into a meta-model.Data sourcesWe searched Medline and EMBASE databases from inception to June 2020.Study eligibility criteriaWe included studies that developed or updated a prognostic model of postoperative mortality in patient with IE.MethodsWe assessed the risk of bias of the models using PROBAST (Prediction model Risk Of Bias ASsessment Tool) and we aggregated them into an aggregate meta-model based on stacked regressions and optimized it for a nationwide registry of IE patients. The meta-model performance was assessed using bootstrap validation methods and adjusted for optimism.ResultsWe identified 11 prognostic models for postoperative mortality. Eight models had a high risk of bias. The meta-model included weighted predictors from the remaining three models (EndoSCORE, specific ES-I and specific ES-II), which were not rated as high risk of bias and provided full model equations. Additionally, two variables (age and infectious agent) that had been modelled differently across studies, were estimated based on the nationwide registry. The performance of the meta-model was better than the original three models, with the corresponding performance measures: C-statistics 0.79 (95% CI 0.76–0.82), calibration slope 0.98 (95% CI 0.86–1.13) and calibration-in-the-large –0.05 (95% CI –0.20 to 0.11).ConclusionsThe meta-model outperformed published models and showed a robust predictive capacity for predicting the individualized risk of postoperative mortality in patients with IE.Protocol registrationPROSPERO (registration number CRD42020192602). 相似文献
75.
Montse Gil-Girbau Mariona Pons-Vigués Maria Rubio-Valera Gabriela Murrugarra Barbara Masluk Beatriz Rodríguez-Martín Atanasio García Pineda Clara Vidal Thomás Sonia Conejo-Cerón José Ignacio Recio Catalina Martínez Enriqueta Pujol-Ribera Anna Berenguera 《Gaceta sanitaria / S.E.S.P.A.S》2021,35(1):48-59
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With increased access to smartphones, the selfie has gained immense popularity in the past decade. Selfie images could be a significant source of ante-mortem (AM) image data in cases where dental records are unavailable or considered insufficient. The application of 3D imaging and selfies has not been explored to its full potential in human dental identification. The present study aimed to evaluate the feasibility of using selfies as AM data and comparing with 3D post-mortem (PM) scans as an alternative to multiple 2D PM photographs in forensic dental identification. The study sample consisted of 18 selfies (12 matching and 6 non-matching) and 15 3D dental scans obtained from the study participants. The study sample was assessed by 6 experienced forensic odontologists (Raters) in two phases; Phase I-Visual comparison of 2D selfies to 3D scans and Phase II-2D selfies superimposed upon 3D scans. Each rater looked at 15 cases, and a total of 1620 comparisons were made by 6 raters (72 for the 12 matching cases and 1548 were for non-matching) and the opinions for each of the comparisons were analyzed. The results of the study show that use of the 3D superimposition method increased the certainty of the conclusions reached by the raters for the cases with correct matches. Furthermore, 94.2% of the 1548 non-matching comparisons were correctly excluded, compared with 77% for the 2D visual comparison method. The study demonstrated the applicability of this 3D method as a valuable tool in assisting the forensic odontologist with dental identification using selfies. 相似文献
79.
目的研究阿托伐他汀联合尿激酶溶栓对大鼠大脑中动脉急性脑梗死的疗效。方法选择SD大鼠48只,采用血栓栓塞法制备大鼠大脑中动脉急性脑梗死模型,随机分为阿托伐他汀组、尿激酶组、联合治疗组和对照组,每组12只。缺血3h给予阿托伐他汀或生理盐水,缺血4h给予尿激酶或生理盐水治疗。治疗前和缺血24h行神经功能缺损评分,缺血24h取脑行2,3,5-氯化三苯基四氮唑染色检测脑梗死体积。结果与对照组比较,阿托伐他汀组缺血24h神经功能显著改善[(6.5±4.3)分vs(12.5±4.3)分],脑梗死体积明显降低[(13.8±7.5)%vs(30.5±23.4)%,P<0.05]。与阿托伐他汀组比较,尿激酶组和联合治疗组神经功能改善程度及脑梗死体积降低程度更显著(P<0.05)。与尿激酶组比较,联合治疗组神经功能改善、脑梗死体积减小,但差异无统计学意义(P>0.05)。结论阿托伐他汀对脑梗死组织有保护作用,阿托伐他汀与尿激酶联合治疗有进一步提高疗效的趋势。 相似文献
80.
《Journal of the American College of Radiology》2015,12(2):151-154
Every year, multiple open-microphone sessions are hosted at the ACR AMCLC. These sessions allow members of the College to offer opinions, experiences, and questions regarding challenges facing radiologists and the future of the profession. At the 2014 AMCLC, 3 such sessions focused, respectively, on radiology’s workforce, the obstacles slowing the shift from volume to value, and alternative reimbursement models and the shifting physician employment landscape. These open-microphone sessions framed contemporary obstacles and emerging challenges that professional radiology societies, such as the ACR, should target with new initiatives and use of resources; in addition, the sessions revealed opportunities for members, councilors, and state chapters to respond with meaningful resolutions and policy proposals. 相似文献