Selectivity and Metaplasticity in a Unified Calcium-Dependent Model

A unified, biophysically motivated Calcium-Dependent Learning model has been shown to account for various rate-based and spike time-dependent paradigms for inducing synaptic plasticity. Here, we investigate the properties of this model for a multi-synapse neuron that receives inputs with different spike-train statistics. In addition, we present a physiological form of metaplasticity, an activity-driven regulation mechanism, that is essential for the robustness of the model. A neuron thus implemented develops stable and selective receptive fields, given various input statistic

Selective cell death of latently HIV-infected CD4+ T cells mediated by autosis inducing nanopeptides.

Despite significant advances in the treatment of human immunodeficiency virus type-1 (HIV) infection, antiretroviral therapy only suppresses viral replication but is unable to eliminate infection. Thus, discontinuation of antiretrovirals results in viral reactivation and disease progression. A major reservoir of HIV latent infection resides in resting central memory CD4+ T cells (TCM) that escape clearance by current therapeutic regimens and will require novel strategies for elimination. Here, we evaluated the therapeutic potential of autophagy-inducing peptides, Tat-Beclin 1 and Tat-vFLIP-α2, which can induce a novel Na+/K+-ATPase dependent form of cell death (autosis), to kill latently HIV-infected TCM while preventing virologic rebound. In this study, we encapsulated autophagy inducing peptides into biodegradable lipid-coated hybrid PLGA (poly lactic-co-glycolic acid) nanoparticles for controlled intracellular delivery. A single dose of nanopeptides was found to eliminate latent HIV infection in an in vitro primary model of HIV latency and ex vivo using resting CD4+ T cells obtained from peripheral blood mononuclear cells of HIV-infected patients on antiretroviral with fully suppressed virus for greater than 12 months. Notably, increased LC3B lipidation, SQSTM1/p62 degradation and Na+/K+-ATPase activity characteristic of autosis, were detected in nanopeptide treated latently HIV-infected cells compared to untreated uninfected or infected cells. Nanopeptide-induced cell death could be reversed by knockdown of autophagy proteins, ATG5 and ATG7, and inhibition or knockdown of Na+/K+-ATPase. Importantly, viral rebound was not detected following the induction of the Na+/K+-ATPase dependent form of cell death induced by the Tat-Beclin 1 and Tat-vFLIP-α2 nanopeptides. These findings provide a novel strategy to eradicate HIV latently infected resting memory CD4+ T cells, the major reservoir of HIV latency, through the induction of Na+/K+-ATPase dependent autophagy, while preventing reactivation of virus and new infection of uninfected bystander cells

Comparison of the on-hand and off-hand straight spikes in volleyball

The purpose of this study was twofold: 1) to examine the differences between the on-hand side and off-hand side spikes in volleyball in terms of velocity and accuracy, and 2) to evaluate the relationship of the angle of projection with velocity in each spike. The subjects (N=12) were members of 1979-80 University of Alberta Volleyball Team. The research design employed a repeated measures technique with two variables, the on-hand and off-hand spikes. Subjects were required to perform 20 straight spikes for each technique. The velocity and the angle of projection data for each trial were obtained by cinematographical analysis. Accuracy scores were collected by direct recording after each trial. A correlated t test was used to determine the differences in velocity and accuracy between the on-hand and the off-hand spikes. A Pearson Product-moment Correlation Coefficient was used to assess the relationship between the velocity and the angle of projection of each spiking technique for each subject. A further correlated t test was used to determine differences in that relationship between the on-hand and off-hand spikes. The results indicated that the differences between the on-hand and off-hand spikes, in terms of velocity and accuracy, were significant (P < .05). There was no relationship between the velocity and the angle of projection for the on-hand spike but a low significant relationship was observed for the off-hand spike. The difference in relationship of velocity and angle of projection between both spiking techniques was not significant. Several recommendations for future researches in this area were offered

Depression in Chinese patients with type 2 diabetes: associations with hyperglycemia, hypoglycemia, and poor treatment adherence.

BackgroundWe hypothesize that depression in type 2 diabetes might be associated with poor glycemic control, in part due to suboptimal self-care. We tested this hypothesis by examining the associations of depression with clinical and laboratory findings in a multicenter survey of Chinese type 2 diabetic patients.Method2538 patients aged 18-75 years attending hospital-based clinics in four cities in China underwent detailed clinical-psychological-behavioral assessment during a 12-month period between 2011 and 2012. Depression was diagnosed if Patient Health Questionnaire-9 (PHQ-9) score ≥10. Diabetes self-care and medication adherence were assessed using the Summary of Diabetes Self-care Activities and the 4-item Morisky medication adherence scale respectively.ResultsIn this cross-sectional study (mean age: 56.4 ± 10.5[SD] years, 53% men), 6.1% (n = 155) had depression. After controlling for study sites, patients with depression had higher HbA(1c) (7.9 ± 2.0 vs. 7.7 ± 2.0%, P = 0.008) and were less likely to achieve HbA(1c) goal of &lt;7.0% (36.2% vs 45.6%, P = 0.004) than those without depression. They were more likely to report hypoglycemia and to have fewer days of being adherent to their recommended diet, exercise, foot care and medication. In logistic regression, apart from young age, poor education, long disease duration, tobacco use, high body mass index, use of insulin, depression was independently associated with failure to attain HbA(1c) target (Odds Ratio [OR] = 1.56, 95%CI:1.05-2.32, P = 0.028). The association between depression and glycemic control became non-significant after inclusion of adherence to diet, exercise and medication (OR = 1.48, 95% CI 0.99-2.21, P = 0.058).ConclusionDepression in type 2 diabetes was closely associated with hyperglycemia and hypoglycemia, which might be partly mediated through poor treatment adherence

Is acupuncture effective in controlling gagging when taking an alginate impressions?

Our community health project aimed to (1) identify the prevalence of gagging among patients attending the Prince Philip Dental Hospital; and to identify socio-demographic variations in reported gagging experiences; and (2) perform a pilot study to evaluate the effectiveness of acupuncture in the control of gagging in the dental setting. Methods: A survey on reported gagging experiences was conducted among patients attending our hospital involving a convenience sample of 225 patients. Participants who reported to previously gag in the dental setting were invited to participate in a pilot study to evaluate the effectiveness of acupuncture in controlling gagging when taking an upper alginate impression. Participants were randomized to receive acupuncture stimulation at a site reported to be effective in the control of gagging on the lower lip (point CV 24) or at a sham site on the upper lip (point GV 26) on their first visit and at their second visit to receive the alternative acupuncture stimulation. Results: The response rate to the survey was 81.3% (183/225). Approximately a third (58/183) reported to have experienced gagging in the dental setting and most frequently encountered this when having a dental impression (among approximately a quarter of participants - 44/183). Half (95/183) reported gagging while performing oral self-care. Four in ten participants (73/183) reported some stress visiting the dentist related to gagging. Sociodemographic variations in reported gagging experiences were evident with respect to age, gender and education level. The response rate to the pilot study was 92.3% (36/39). There was no significant difference in the prevalence of gagging when acupuncture was applied to the test site compared to when acupuncture was applied to the sham site on dental examination (p>0.05) or when taking an upper alginate impression (p>0.05). Conclusions: Gagging in a relative common experience reported by patients attending our hospital – in daily life, in the dental setting and in performing oral self-care. Socio-demographic variations in the prevalence of gagging were apparent. The pilot study does not support the use of acupuncture in controlling gagging in the dental setting.published_or_final_versio

iCartiGD: the Integrated Cartilage Gene Database

BACKGROUND: Diseases of cartilage, such as arthritis and degenerative disc disease, affect the majority of the general population, particularly with ageing. Discovery and understanding of the genes and pathways involved in cartilage biology will greatly assist research on the development, degeneration and disorders of cartilage. DESCRIPTION: We have established the Integrated Cartilage Gene Database (iCartiGD) of genes that are known, based on results from high throughput experiments, to be expressed in cartilage. Information about these genes is extracted automatically from public databases and presented as a single page report via a web-browser. A variety of flexible search options are provided and the chromosomal distribution of cartilage associated genes can be presented. CONCLUSION: iCartiGD provides a comprehensive source of information on genes known to be expressed in cartilage. It will remain current due to its automatic update capability and provide researchers with an easily accessible resource for studies involving cartilage. Genetic studies of the development and disorders of cartilage will benefit from this database

Enhanced detection of early hepatocellular carcinoma by serum SELDI-TOF proteomic signature combined with alpha-fetoprotein marker.

BACKGROUND: Biomarkers for accurate diagnosis of early hepatocellular carcinoma (HCC) are limited in number and clinical validation. We applied SELDI-TOF-MS ProteinChip technology to identify serum profile for distinguishing HCC and liver cirrhosis (LC) and to compare the accuracy of SELDI-TOF-MS profile and alpha-fetoprotein (AFP) level in HCC diagnosis. PATIENTS AND METHODS: Serum samples were obtained from 120 HCC and 120 LC patients for biomarker discovery and validation studies. ProteinChip technology was employed for generating SELDI-TOF proteomic features and analyzing serum proteins/peptides. RESULTS: A diagnostic model was established by CART algorithm, which is based on 5 proteomic peaks with m/z values at 3324, 3994, 4665, 4795, and 5152. In the training set, the CART algorithm could differentiate HCC from LC subjects with a sensitivity and specificity of 98% and 95%, respectively. The results were assessed in blind validation using separate cohorts of 60 HCC and 60 LC patients, with an accuracy of 83% for HCC and 92% for LC patients. The diagnostic odd ratio (DOR) indicated that SELDI-TOF proteomic signature could achieve better diagnostic performance than serum AFP level at a cutoff of 20 ng/mL (AFP(20)) (92.72 vs 9.11), particularly superior for early-stage HCC (87% vs 54%). Importantly, a combined use of both tests could enhance the detection of HCC (sensitivity, 95%; specificity, 98%; DOR, 931). CONCLUSION: Serum SELDI-TOF proteomic signature, alone or in combination with AFP marker, promises to be a good tool for early diagnosis and/screening of HCC in at-risk population with liver cirrhosis

Effects of Long Distance Cycling in a Hot Ambient Temperature on White Blood Cell Count

Ultra-endurance events under extreme heat conditions have become popular. Prolonged exercise imposes a transient physiological stress on the immune system; this stress is augmented when exercising in hot ambient temperature conditions. To date, no field study has investigated the immune response to ultra-endurance cycling under extreme heat conditions. To determine the effect of completing a 164km cycling event in a hot ambient temperature on white blood cell count. Thirty-nine experienced cyclists (36 men and 3 women; 49.4 ± 8.6 yr, 83.0 ± 15.0 kg, 176.2 ± 7.3 cm, 19.9 ± 6.6% body fat) participating in the August 2013 Hotter’N Hell Hundred ride held in Wichita Falls, TX, were recruited. Blood samples were collected within 2 hours of the start (PRE; ~0500-0700h) and immediately after completion (POST) of the event. During the event there was minimal cloud cover and the wet bulb globe temperature was 31.4 ± 3.8 ̊C with a maximum of 36.1 ̊C. Samples were analyzed for complete blood count with partial differential. To examine the effect of (a) duration of heat exposure and (b) change in plasma volume, participants were grouped and compared based on finishing time (fastest and slowest 25th percentile) as well as on plasma volume (PV) change (\u3e10, 1-10, and \u3c0%). Total white blood cell (PRE: 5.54 ± 0.23; POST; 12.12 ± 0.46 x 109 L-1), lymphocyte (PRE: 2.47 ± 0.1; POST: 3.52 ± 0.22 x 109 L-1), mid-size range cells (MID) (PRE: 1.27 ± 0.08; POST: 1.49 ± 0.1 x 109 L-1), and granulocyte (PRE: 1.81 ± 0.11; POST: 7.11 ± 0.41 x 109 L-1) increased significantly (p \u3c 0.05) from PRE to POST. This change resulted in a significant decrease in %lymphocytes (PRE: 44.63 ± 1.19; POST: 29.45 ± 1.62%) and %MID (PRE: 23.41 ± 0.79; POST: 12.89 ± 0.86%) and a significant increase in %granulocytes (PRE: 31.96 ± 1.02; POST: 57.66 ± 1.99%) in circulation. No differences were observed for leukocyte subsets between the fastest and slowest 25th percentile finishers or among groups based on PV change. Prolonged cycling (164km) in a hot environment induced changes in abundance of the major circulating immune cell populations; these changes were independent of exercise duration/intensity or PV change