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101.
《Clinical neurophysiology》2020,131(1):213-224
ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology. 相似文献
102.
Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma 下载免费PDF全文
Georgia Levidou Dimitrios Theodorou Nikolaos V. Michalopoulos Efstratios Patsouris Angelica A. Saetta 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(8):639-647
Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings. 相似文献
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《Vaccine》2020,38(39):6141-6152
Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4+ and CD8+ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity. 相似文献
107.
Anand Dayama Nikolaos Tsilimparis Stephen Kolakowski Nathaniel M. Matolo Misty D. Humphries 《Journal of vascular surgery》2019,69(1):156-163.e1
Background
Chronic limb-threatening ischemia (CLTI), defined as ischemic rest pain or tissue loss secondary to arterial insufficiency, is caused by multilevel arterial disease with frequent, severe infrageniculate disease. The rise in CLTI is in part the result of increasing worldwide prevalence of diabetes, renal insufficiency, and advanced aging of the population. The aim of this study was to compare a bypass-first with an endovascular-first revascularization strategy in patients with CLTI due to infrageniculate arterial disease.Methods
We reviewed the American College of Surgeons National Surgical Quality Improvement Program targeted lower extremity revascularization database from 2012 to 2015 to identify patients with CLTI and isolated infrageniculate arterial disease who underwent primary infrageniculate bypass or endovascular intervention. We excluded patients with a history of ipsilateral revascularization and proximal interventions. The end points were major adverse limb event (MALE), major adverse cardiovascular event (MACE), amputation at 30 days, reintervention, patency, and mortality. Multivariable logistic regression was used to determine the association of a bypass-first or an endovascular-first intervention with outcomes.Results
There were 1355 CLTI patients undergoing first-time revascularization to the infrageniculate arteries (821 endovascular-first revascularizations and 534 bypass-first revascularizations) identified. There was no significant difference in adjusted rate of 30-day MALE in the bypass-first vs endovascular-first revascularization cohort (9% vs 11.2%; odds ratio [OR], 0.73; 95% confidence interval [CI], 0.50-1.08). However, the incidence of transtibial or proximal amputation was lower in the bypass-first cohort (4.3% vs 7.4%; OR, 0.60; CI, 0.36-0.98). Patients with bypass-first revascularization had higher wound complication rates (9.7% vs 3.7%; OR, 2.75; CI, 1.71-4.42) compared with patients in the endovascular-first cohort. Compared with the endovascular-first cohort, the incidence of 30-day MACE was significantly higher in bypass-first patients (6.9% vs 2.6%; adjusted OR, 3.88; CI, 2.18-6.88), and 30-day mortality rates were 3.23% vs 1.8% (adjusted OR, 2.77; CI, 1.26-6.11). There was no difference in 30-day untreated loss of patency, reintervention of treated arterial segment, readmissions, and reoperations between the two cohorts. In subgroup analysis after exclusion of dialysis patients, there was also no significant difference in MALE or amputation between the bypass-first and endovascular-first cohorts.Conclusions
CLTI patients with isolated infrageniculate arterial disease treated by a bypass-first approach have a significantly lower 30-day amputation. However, this benefit was not observed when dialysis patients were excluded. The bypass-first cohort had a higher incidence of MACE compared with an endovascular-first strategy. These results reaffirm the need for randomized controlled trials, such as the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL-2) trial and Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI), to provide level 1 evidence for the role of endovascular-first vs bypass-first revascularization strategies in the treatment of this population of challenging patients. 相似文献108.
《Arquivos brasileiros de cardiologia》2020,115(2):207
BackgroundTakotsubo syndrome (TTS) is an acquired form of cardiomyopathy. National Brazilian data on this condition are scarce. The Takotsubo Multicenter Registry (REMUTA) is the first to include multicenter data on this condition in Brazil.ObjectiveTo describe the clinical characteristics, prognosis, in-hospital treatment, in-hospital mortality, and mortality during 1 year of follow-up.MethodsThis is an observational, retrospective registry study including patients admitted to the hospital with diagnosis of TTS and patients admitted for other reasons who developed this condition. Evaluated outcomes included triggering factor, analysis of exams, use of medications, complications, in-hospital mortality, and mortality during 1 year of follow-up. A significance level of 5% was adopted.ResultsThe registry included 169 patients from 12 centers in the state of Rio de Janeiro, Brazil. Mean age was 70.9 ± 14.1 years, and 90.5% of patients were female; 63% of cases were primary TTS, and 37% were secondary. Troponin I was positive in 92.5% of patients, and median BNP was 395 (176.5; 1725). ST-segment elevation was present in 28% of patients. Median left ventricular ejection fraction was 40 (35; 48)%. We observed invasive mechanical ventilation in 25.7% of cases and shock in 17.4%. Mechanical circulatory support was used in 7.7%. In-hospital mortality was 10.6%, and mortality at 1 year of follow-up was 16.5%. Secondary TTS and cardiogenic shock were independent predictors of mortality.ConclusionThe results of the REMUTA show that TTS is not a benign pathology, as was once thought, especially regarding the secondary TTS group, which has a high rate of complications and mortality. (Arq Bras Cardiol. 2020; 115(2):207-216) 相似文献
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《Alzheimer's & dementia》2019,15(12):1507-1515
IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos. 相似文献