Effect of inter-train interval on the induction of repetition suppression of motor-evoked potentials using transcranial magnetic stimulation

by Minna Pitkänen, Elisa Kallioniemi, Petro Julkunen

Repetition suppression (RS) is evident as a weakened response to repeated stimuli after the initial response. RS has been demonstrated in motor-evoked potentials (MEPs) induced with transcranial magnetic stimulation (TMS). Here, we investigated the effect of inter-train interval (ITI) on the induction of RS of MEPs with the attempt to optimize the investigative protocols. Trains of TMS pulses, targeted to the primary motor cortex by neuronavigation, were applied at a stimulation intensity of 120% of the resting motor threshold. The stimulus trains included either four or twenty pulses with an inter-stimulus interval (ISI) of 1 s. The ITI was here defined as the interval between the last pulse in a train and the first pulse in the next train; the ITIs used here were 1, 3, 4, 6, 7, 12, and 17 s. RS was observed with all ITIs except with the ITI of 1 s, in which the ITI was equal to ISI. RS was more pronounced with longer ITIs. Shorter ITIs may not allow sufficient time for a return to baseline. RS may reflect a startle-like response to the first pulse of a train followed by habituation. Longer ITIs may allow more recovery time and in turn demonstrate greater RS. Our results indicate that RS can be studied with confidence at relatively short ITIs of 6 s and above.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2vk8EOW

Crystal structure and functional characterization of an isoaspartyl dipeptidase (CpsIadA) from Colwellia psychrerythraea strain 34H

by Sun-Ha Park, Chang Woo Lee, Sung Gu Lee, Seung Chul Shin, Hak Jun Kim, Hyun Park, Jun Hyuck Lee

Isoaspartyl dipeptidase (IadA) is an enzyme that catalyzes the hydrolysis of an isoaspartyl dipeptide-like moiety, which can be inappropriately formed in proteins, between the β-carboxyl group side chain of Asp and the amino group of the following amino acid. Here, we have determined the structures of an isoaspartyl dipeptidase (CpsIadA) from Colwellia psychrerythraea, both ligand-free and that complexed with β-isoaspartyl lysine, at 1.85-Å and 2.33-Å resolution, respectively. In both structures, CpsIadA formed an octamer with two Zn ions in the active site. A structural comparison with Escherichia coli isoaspartyl dipeptidase (EcoIadA) revealed a major difference in the structure of the active site. For metal ion coordination, CpsIadA has a Glu166 residue in the active site, whereas EcoIadA has a post-translationally carbamylated-lysine 162 residue. Site-directed mutagenesis studies confirmed that the Glu166 residue is critical for CpsIadA enzymatic activity. This residue substitution from lysine to glutamate induces the protrusion of the β12-α8 loop into the active site to compensate for the loss of length of the side chain. In addition, the α3-β9 loop of CpsIadA adopts a different conformation compared to EcoIadA, which induces a change in the structure of the substrate-binding pocket. Despite CpsIadA having a different active-site residue composition and substrate-binding pocket, there is only a slight difference in CpsIadA substrate specificity compared with EcoIadA. Comparative sequence analysis classified IadA-containing bacteria and archaea into two groups based on the active-site residue composition, with Type I IadAs having a glutamate residue and Type II IadAs having a carbamylated-lysine residue. CpsIadA has maximal activity at pH 8–8.5 and 45°C, and was completely inactivated at 60°C. Despite being isolated from a psychrophilic bacteria, CpsIadA is thermostable probably owing to its octameric structure. This is the first conclusive description of the structure and properties of a Type I IadA.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2uDhWaM

Social sensing of urban land use based on analysis of Twitter users’ mobility patterns

by Aiman Soliman, Kiumars Soltani, Junjun Yin, Anand Padmanabhan, Shaowen Wang

A number of recent studies showed that digital footprints around built environments, such as geo-located tweets, are promising data sources for characterizing urban land use. However, challenges for achieving this purpose exist due to the volume and unstructured nature of geo-located social media. Previous studies focused on analyzing Twitter data collectively resulting in coarse resolution maps of urban land use. We argue that the complex spatial structure of a large collection of tweets, when viewed through the lens of individual-level human mobility patterns, can be simplified to a series of key locations for each user, which could be used to characterize urban land use at a higher spatial resolution. Contingent issues that could affect our approach, such as Twitter users' biases and tendencies at locations where they tweet the most, were systematically investigated using 39 million geo-located Tweets and two independent datasets of the City of Chicago: 1) travel survey and 2) parcel-level land use map. Our results support that the majority of Twitter users show a preferential return, where their digital traces are clustered around a few key locations. However, we did not find a general relation among users between the ranks of locations for an individual—based on the density of tweets—and their land use types. On the contrary, temporal patterns of tweeting at key locations were found to be coherent among the majority of users and significantly associated with land use types of these locations. Furthermore, we used these temporal patterns to classify key locations into generic land use types with an overall classification accuracy of 0.78. The contribution of our research is twofold: a novel approach to resolving land use types at a higher resolution, and in-depth understanding of Twitter users' location-related and temporal biases, promising to benefit human mobility and urban studies in general.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2uJodSX

Barriers and facilitators of HIV vaccine and prevention study participation among Young Black MSM and transwomen in New York City

by Sharise Richardson, Pich Seekaew, Beryl Koblin, Tasha Vazquez, Vijay Nandi, Hong-Van Tieu

Background

Black men who have sex with men (MSM), and Transwomen (TW) shoulder disproportionate burden of HIV. However, they are unrepresented in HIV vaccine trials. We investigated the perceptions of that factors associated with HIV vaccine trials participation among Black MSM and TW in New York.

Methods

Self-administered online questionnaires were administered to 18–29 years of NYC residents who identified as Black MSM and TW, assessing demographics, awareness and willingness to participate in HIV vaccine trials, barriers and facilitators associated with willingness, and sexual behaviors. Frequency summation was performed to determine barriers and facilitators, and logistic regression analysis was performed to determine factors association with expressed willingness.

Results

Black MSM and TW who reported engaging in risk behaviors had a 61% lower likelihood of participating in HIV vaccine trials when compared to those who did not report engaging in any risk behavior. Facilitators associated with trial participation were: cash compensation, confidentiality regarding participation, public transportation vouchers, gift cards, and food or grocery vouchers as potential facilitators for trial participation. Conversely, fear of side effects from the vaccine, concerns about testing positive on routine HIV testing due to an HIV vaccine, limited knowledge of research trials, and fear of being judged as HIV-positive were perceived as barriers.

Conclusions

These findings provided insights into the considerations and perceptions of Black MSM and TW towards HIV vaccine trials. However, further studies are needed to delineate the complex mechanisms underlying the decision-making process and establish approaches to increase study participation in this population.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2vDeB8K

Correction: Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress

by Jingjing Liang, Cari A. Sagum, Mark T. Bedford, Sachdev S. Sidhu, Marius Sudol, Ziying Han, Ronald N. Harty

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2uJ85kt

Correction: Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress

by Jingjing Liang, Cari A. Sagum, Mark T. Bedford, Sachdev S. Sidhu, Marius Sudol, Ziying Han, Ronald N. Harty

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2uJ85kt

Dabigatran and vitamin K antagonists’ use in naïve patients with non-valvular atrial fibrillation: a cross-sectional study of primary care-based electronic health records

Abstract

Purpose

The purpose of this study was to characterize the profile of patients with non-valvular atrial fibrillation who start an anticoagulant treatment after diagnosis with dabigatran and compare it with those who start with vitamin K antagonists (VKAs).

Methods

We analysed primary health care-based electronic health records data from 15,075 people with new diagnosis of atrial fibrillation who initiated treatment with dabigatran or VKA spanning 2011–2013. Logistic regression analysis for determination of factors associated with initiation of dabigatran was performed.

Results

We identified 14,266 (94.6%) people who initiated VKA and 809 (5.4%) who initiated dabigatran. Mean age of people treated with dabigatran was lower than in VKA patients (73.7 vs 75.5 years, p < 0.001). People (90.5%) in VKA group and 83.6% in the dabigatran group had a high risk of stroke, according to CHA₂DS₂VASc score. There was higher proportion of people with hypertension, diabetes mellitus, dyslipidaemia, and chronic kidney disease among people treated with VKA. The proportion of people with a history of cerebral haemorrhage and stroke was higher among dabigatran patients compared with VKA patients (1.4 vs 0.6%, p = 0.015 and 14.0% vs 10.8%, p = 0.006, respectively). Multivariable logistic model showed that treatment with dabigatran was associated with male sex, history of stroke and Mortalidad en áreas pequeñas Españolas y Desigualdades Socioeconómicas index.

Conclusions

Most patients recently diagnosed with non-valvular atrial fibrillation initiated treatment with VKA. Primary healthcare patients with non-valvular atrial fibrillation initiating dabigatran are younger, had a lower risk of stroke or bleeding, fewer comorbidity and more history of stroke and intracranial haemorrhage compared to those who were initiated on VKA.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2tHB573