Lack of Association Between Total Serum Homocysteine and Extracranial Cerebral Flow

Background/PurposeHigh homocysteine (Hcy) concentration is associated with slow coronary flow. This study examined the association between Hcy and hemodynamic status in the extracranial cerebral arteries in healthy individuals.MethodsA total of 535 healthy adults underwent physical examination and duplex ultrasonography of the extracranial carotid and vertebral arteries, and blood laboratory tests, including biochemistry and serum total Hcy. Flow hemodynamic parameters including velocity, resistance, and volume of the carotid and vertebral arteries were measured. Multiple regression analysis was performed to examine the association between Hcy and the flow parameters.ResultsParticipants with higher Hcy were more likely to have a lower systolic velocity of the internal carotid artery (p = 0.01) and vertebral artery (p < 0.001), and lower resistance of the vertebral artery (p = 0.004). However, the multiple-adjusted means of the flow velocity, resistance, and flow volume of the carotid or vertebral artery were not significantly different across quartiles of Hcy. When Hcy was treated as a continuous variable, there was still no significant relationship between Hcy levels and the aforementioned hemodynamic status.ConclusionOur results did not support the hypothesis that the levels of Hcy are associated with the flow velocity, resistance, and volume of the extracranial cerebral artery in healthy individuals

Identification of a forebrain motor programming network for the learned song of zebra finches

The stereotyped delivery of sequences of vocalizations by singing zebra finches is thought to be mediated by a “central motor program.” We hypothesized that electrically stimulating, and thus perturbing, the neural components of this motor program during singing should alter the subsequent singing pattern. In contrast, perturbing the activity of other neurons in the song motor pathway that do not participate directly in generating the song temporal pattern should not affect the singing pattern. We found that unilaterally stimulating the forebrain area RA of singing birds with chronically implanted electrodes distorted ongoing syllables without changing the order or timing of ensuing syllables. However, stimulating forebrain area HVc, which projects directly to RA, altered both ongoing syllables and the ensuing song pattern. These findings indicate that syllable sequencing during singing is organized in forebrain areas above RA (including HVc) and that the resulting pattern is imposed on lower structures of the motor pathway. Furthermore, the observation that unilateral forebrain perturbation was sufficient to alter the pattern of this bilaterally organized behavior suggests that (non-auditory) feedback pathways to the forebrain exist to coordinate the two hemispheres during singing. We suggest that the study of the motor control system for birdsong has provided the most direct evidence to date for localizing the programming of a skilled motor sequence to the telencephalon

T Oligo-Primed Polymerase Chain Reaction (TOP-PCR): A Robust Method for the Amplification of Minute DNA Fragments in Body Fluids.

Body fluid DNA sequencing is a powerful noninvasive approach for the diagnosis of genetic defects, infectious agents and diseases. The success relies on the quantity and quality of the DNA samples. However, numerous clinical samples are either at low quantity or of poor quality due to various reasons. To overcome these problems, we have developed T oligo-primed polymerase chain reaction (TOP-PCR) for full-length nonselective amplification of minute quantity of DNA fragments. TOP-PCR adopts homogeneous "half adaptor" (HA), generated by annealing P oligo (carrying a phosphate group at the 5' end) and T oligo (carrying a T-tail at the 3' end), for efficient ligation to target DNA and subsequent PCR amplification primed by the T oligo alone. Using DNA samples from body fluids, we demonstrate that TOP-PCR recovers minute DNA fragments and maintains the DNA size profile, while enhancing the major molecular populations. Our results also showed that TOP-PCR is a superior method for detecting apoptosis and outperforms the method adopted by Illumina for DNA amplification

Case report: Heterogenous SMARCA4-deficient thoracic non-small cell lung carcinoma with various responses to nivolumab

SMARCA4-deficient non-small cell carcinoma is an aggressive neoplasm with poor outcome. Several studies have highlighted its immunochemistry, pathophysiology, and underlying mechanisms, but studies of its definite treatment are few. Here, we report on a 69-year-old male with heterogenous pathological presentations of SMARCA4-deficient non-small cell carcinoma. He initially presented with neck lymphadenopathies. Immunohistochemistry staining and genomic profiling confirmed the diagnosis of SMARCA4-deficient non-small cell carcinoma. The patient responded well to immune checkpoint inhibitors with nivolumab. However, new lesions with various pathological presentations and various responses to nivolumab appeared during the treatment course. The patient survived more than 3 years from the initial diagnosis. This case shows the efficacy of nivolumab to treat SMARCA4-deficient non-small cell lung carcinoma

Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes

Undiagnosed diabetes mellitus among residents in Taiwanese long-term care facilities: A comparison of fasting glucose, postprandial plasma glucose, and hemoglobin A1c

AbstractBackgroundThe prevalence of diabetes mellitus (DM) is escalating with an aging population, and the chances of diabetic older patients admitted to long-term care facilities (LTCFs) are increased because of DM-related complications. However, undiagnosed DM among LTCF residents is a recognized hidden problem in this setting and may result in adverse outcomes.MethodsIn May 2011, 10 private LTCFs in northern Taipei participated in this study. Trained research nurses reviewed the medical records and performed physical examinations and blood sampling for all participants. Diabetes mellitus was diagnosed, based on the levels of fasting glucose, 2-hour postprandial plasma glucose, and hemoglobin A1c (HbA1c). Patients were categorized as having DM if they met the diagnostic cut-offs of the aforementioned criteria.ResultsOne hundred and ninety-nine residents (mean age, 79.6 ± 10.5 years; 52.3% males) participated in this study. They were all moderately/severely disabled (Karnofsky Performance Scale mean score was 50 ± 13). Forty-six (23.1%) residents were diabetic, based on their medical records, or were current users of antidiabetic agents. The prevalence was 29.6% after testing with a mean HbA1c level of 6.9% ± 0.9%. The overall undiagnosed DM rate was 4%, 3.5%, and 4.5%, based on fasting glucose, 2-hour postprandial plasma glucose, and HbA1c criteria, respectively. Diabetic patients had significantly higher serum levels of prealbumin, compared to nondiabetic patients (220.8 ± 45.9 vs. 201.1 ± 62.2 mg/L; p = 0.03), but there were no differences in the levels of hemoglobin, serum albumin, or total cholesterol. Diabetic patients had a significantly higher serum triglyceride level, compared to the nondiabetic patients (1.6 ± 0.7 vs. 1.1 ± 0.5 mmol/L; p < 0.01) and a lower high-density lipoprotein level (1.0 ± 0.3 vs. 1.2 ± 0.3 mmol/L; p < 0.01). Among 43 pharmacologically treated diabetic patients, 65.1% (28/43) of patients were using oral antidiabetic agents and 41.9% (18/43) of patients had been prescribed insulin, whereas 32.6% of the patients were managed by combination therapy.ConclusionThe prevalence of DM among LTCF residents in Taipei was 29.6%, and the undiagnosed rate was no more than 5%, based on fasting glucose, 2-hour postprandial plasma glucose, or HbA1c. Further study is needed for the optimal treatment strategy of DM in LTCFs

Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

BACKGROUND: Triglyceride/HDL cholesterol ratio (TG/HDL-C) is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C. RESULTS: Two populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs) and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs) were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0). Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 ± 0.114, p = 0.002), but the common shared environmental factor was higher in hospital-based families (0.203 ± 0.042, p < 0.001). Commingling analyses showed that more than one-component distribution models were the best-fit models to explain the variance in both populations. Complex segregation analysis by regressive models revealed that in both samples the best-fit model of TG/HDL-C was the model of environmental effects plus familial correlation, in which significant parent-offspring and sibling correlations were demonstrated. Models of major gene effects were rejected in both samples. CONCLUSION: Variations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families