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To investigate the effect of rapamycin on mitochondrial dynamic balance in diabetic rats subjected to cerebral ischemia-reperfusion injury. Male Sprague Dawley (SD) rats (n = 78) were treated with high fat diet combined with streptozotocin injection to construct diabetic model in rats. Transient middle cerebral artery occlusion (MCAO) of 2 hours was induced and the brains were harvested after 1 and 3 days of reperfusion. Rapamycin was injected intraperitoneally for 3 days prior to and immediately after operation, once a day. The neurological function was assessed, infarct volumes were measured and HE staining as well as immunohistochemistry were performed. The protein of hippocampus was extracted and Western blotting were performed to detect the levels of mTOR, mitochondrial dynamin related proteins (DRP1, p-DRP1, OPA1), SIRT3, and Nix/BNIP3L. Diabetic hyperglycemia worsened the neurological function performance (p < 0.01), enlarged infarct size (p < 0.01) and increased ischemic neuronal cell death (p < 0.01). The increased damage was associated with elevations of p-mTOR, p-S6, and p-DRP1; and suppressions of SIRT3 and Nix/BNIP3L. Rapamycin ameliorated diabetes-enhanced ischemic brain damage and reversed the biomarker alterations caused by diabetes. High glucose activated mTOR pathway and caused mitochondrial dynamics toward fission. The protective effect of rapamycin against diabetes-enhanced ischemic brain damage was associated with inhibiting mTOR pathway, redressing mitochondrial dynamic imbalance, and elevating SIRT3 and Nix/BNIP3L expression. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is prevalent in certain areas, such as South China, Southeast Asia, and the Middle East. Radiation therapy is the most efficient means to treat this malignant tumor. Positron emission tomography–computed tomography (PET-CT) is a suitable imaging technique to assess this disease. However, the large amount of data produced by numerous patients causes traditional manual delineation of tumor contour, a basic step for radiotherapy, to become time-consuming and labor-intensive. Thus, the demand for automatic and credible segmentation methods to alleviate the workload of radiologists is increasing. This paper presents a method that uses fully convolutional networks with auxiliary paths to achieve automatic segmentation of NPC on PET-CT images. This work is the first to segment NPC using dual-modality PET-CT images. This technique is identical to what is used in clinical practice and offers considerable convenience for subsequent radiotherapy. The deep supervision introduced by auxiliary paths can explicitly guide the training of lower layers, thus enabling these layers to learn more representative features and improve the discriminative capability of the model. Results of threefold cross-validation with a mean dice score of 87.47% demonstrate the efficiency and robustness of the proposed method. The method remarkably outperforms state-of-the-art methods in NPC segmentation. We also validated by experiments that the registration process among different subjects and the auxiliary paths strategy are considerably useful techniques for learning discriminative features and improving segmentation performance. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of OFCD associated with a de novo BCOR pathogenic variant and highlight the ocular findings and possible mechanisms.Methods: A retrospective chart review of the patient's ocular and systemic findings was performed. The patient underwent diagnostic whole exome sequencing (WES).Results: The patient had a comprehensive eye exam in infancy demonstrating bilateral congenital cataracts consisting of posterior lenticonus with a posterior cortical opacity. She also had blepharoptosis with a hooded appearance and retinal pigment hypertrophy of the inferior retina bilaterally. Systemic findings include atrial septal defect, patent ductus arteriosus, congenital clubfoot, syndactyly, tethered cord, and laryngeal cleft. WES identified a de novo heterozygous R1136X pathogenic variant in the BCOR gene.Conclusion: The typical ocular manifestation of OFCD syndrome is congenital cataracts, which can have a significant impact on visual development and so should be considered in patients with multiple medical issues that may fit the diagnosis. A comprehensive eye exam in these patients is thus warranted. [ABSTRACT FROM AUTHOR]

Selective laser trabeculoplasty (SLT) has been widely used in the clinical management of glaucoma, both as primary and adjunctive treatment. As new evidence continues to arise, we review the current literature in terms of indications and efficacy, surgical technique, postoperative care, repeatability, and complications of this therapy. SLT has been shown to be effective in various glaucomas, including primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), steroid-induced glaucoma, pseudoexfoliation glaucoma (PXFG), and primary angle-closure glaucoma (PACG), as well as other glaucoma subtypes. Relatively high preoperative intraocular pressure (IOP) may predict surgical success, while other parameters that have been studied do not seem to affect the outcome. Different techniques for performing the procedure have recently been explored, revealing that minor modifications may lead to a more favorable or safer clinical outcome. The utilization of postoperative medications remains controversial based on the current evidence. A short-term IOP increase may complicate SLT and can also persist in certain cases such as in exfoliation glaucoma. The efficacy and safety of repeat SLT are shown in multiple studies, and the timing of repeat procedures may affect the success rate. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is characterized by alveolar injury and uncontrolled inflammation. Mechanisms underlying pathogenesis of ALI are unknown. Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. In the current study, we investigated whether Tregs were involved in the development of ALI. Proportion of CD4 + CD25 + FoxP3+ Tregs in the peripheral blood of 66 ALI patients and 30 healthy controls were examined by flow cytometry. Data showed that the percentage of Tregs in CD4+ T cells was significantly increased in patients than that in controls (10.8 versus 7.6 %, P = 0.003). Also, compared to those who died during the study, patients who survived presented significantly higher level of Tregs at the time of recruitment ( P = 0.041). Since Tim-3 is a negative regulatory molecule and can modulate the function of Tregs, we evaluated Tim-3 level on Tregs and identified upregulation of the molecule in patients than that in controls. Moreover, compared to those who died during the study, patients who survived showed 1.7-fold higher level of Tim-3 on Tregs at the time of recruitment ( P < 0.001). These results suggest that Tregs could affect the prognosis of ALI probably due to the upregulation of Tim-3. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most lethal cancers worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in tumor immunity. It has been reported that polymorphisms in CD86 gene can be involved in the development of various cancers. Here, we investigated the association of two CD86 polymorphisms, +1057G/A (rs1129055) and +2379G/C (rs17281995), with pancreatic cancer in the Chinese population. Methods: The two polymorphisms were identified in 369 pancreatic cancer patients and 412 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data were analyzed by chi-square test and adjusted for body mass index, smoking, drinking, and diabetes status. Results: Results showed that the frequency of the +1057A allele was significantly higher in pancreatic cancer cases than in controls (59.8 vs. 52.8 %, p = 0.021). Comparison of genotype frequencies showed that +1057GA and +1057AA genotypes were significantly increased in the pancreatic cancer group (odds ratio (OR) = 1.52; 95 % confidence interval (CI), 1.09-2.38; p = 0.026; and OR = 1.90; 95 % CI, 1.21-3.01; p = 0.007). We did not find any association between the +2379G/C polymorphism and pancreatic cancer. Analysis of haplotypes indicated that the AG (+1057, +2379) haplotype was correlated with the susceptibility to this disease ( p = 0.019). Conclusions: These results suggest that the CD86 +1057G/A polymorphism and AG (+1057, +2379) haplotype are genetic risk factors for pancreatic cancer. [ABSTRACT FROM AUTHOR]

T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 cell-mediated immunity. Studies have shown that polymorphisms in TIM-3 gene can be associated with various diseases. Here, we investigated the correlation of TIM-3 polymorphisms with susceptibility to pancreatic cancer in the Chinese population. Three polymorphisms in TIM-3 gene (−1516G/T, −574G/T, and +4259T/G) were identified by polymerase chain reaction-restriction fragment length polymorphism in 306 pancreatic patients and 408 healthy controls. Results showed that the prevalence of +4259TG genotype and +4259G allele were significantly increased in the pancreatic cancer cases than in controls [odds ratio (OR) = 2.82, 95 % confidence interval (CI), 1.45-5.48, p = 0.0015, and OR = 2.74, 95 % CI, 1.42-2.94, p = 0.0017]. In addition, when analyzing the TIM-3 polymorphisms with different clinical parameters in pancreatic cancer patients, the cases with vascular infiltration had higher numbers of +4259T/G polymorphism than those without vascular infiltration (OR = 3.07, 95 % CI, 1.41-6.68, p = 0.003). These results suggested polymorphisms in TIM-3 gene could be new risk factors for the development of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Research on the test-taker perception of assessments has been conducted under the assumption that negative test-taker perception may influence test performance by decreasing test-taking motivation. This assumption, however, has not been verified in the field of language testing. Building on expectancy-value theory, this study explored the relationships between test-taker perception, test-taking motivation, and test performance in the context of a computer-delivered speaking test. Methods: Sixty-four Japanese university students took the TOEIC Speaking test and completed a questionnaire that included statements about their test perception, test-taking motivation, and self-perceived test performance. Five students participated in follow-up interviews. Results: Questionnaire results showed that students regarded the TOEIC Speaking test positively in terms of test validity but showed reservations about computer delivery, and that they felt sufficiently motivated during the test. Interview results revealed various reasons for their reservations about computer delivery and factors that distracted them during the test. According to correlation analysis, the effects of test-taker perception and test-taking motivation seemed to be minimal on test performance, and participants' perception of computer delivery was directly related to test-taking effort, but their perception of test validity seemed to be related to test-taking effort only indirectly through the mediation of perceived test importance. Conclusion: Our findings not only provide empirical evidence for the relationship between test-taker perception and test performance but also highlight the importance of considering test-taker reactions in developing tests. [ABSTRACT FROM AUTHOR]

Theta (4-8 Hz) and gamma (30-80 Hz) rhythms in the brain are commonly associated with memory and learning (Kahana in J Neurosci 26:1669-1672, 2006; Quilichini et al. in J Neurosci 30:11128-11142, 2010). The precision of co-firing between neurons and incoming inputs is critical in these cognitive functions. We consider an inhibitory neuron model with M-current under forcing from gamma pulses and a sinusoidal current of theta frequency. The M-current has a long time constant (∼90 ms) and it has been shown to generate resonance at theta frequencies (Hutcheon and Yarom in Trends Neurosci 23:216-222, 2000; Hu et al. in J Physiol 545:783-805, 2002). We have found that this slow M-current contributes to the precise co-firing between the network and fast gamma pulses in the presence of a slow sinusoidal forcing. The M-current expands the phase-locking frequency range of the network, counteracts the slow theta forcing, and admits bistability in some parameter range. The effects of the M-current balancing the theta forcing are reduced if the sinusoidal current is faster than the theta frequency band. We characterize the dynamical mechanisms underlying the role of the M-current in enabling a network to be entrained to gamma frequency inputs using averaging methods, geometric singular perturbation theory, and bifurcation analysis. [ABSTRACT FROM AUTHOR]