Assessing Neuronal Interactions of Cell Assemblies during General Anesthesia

Understanding the way in which groups of cortical neurons change their individual and mutual firing activity during the induction of general anesthesia may improve the safe usage of many anesthetic agents. Assessing neuronal interactions within cell assemblies during anesthesia may be useful for understanding the neural mechanisms of general anesthesia. Here, a point process generalized linear model (PPGLM) was applied to infer the functional connectivity of neuronal ensembles during both baseline and anesthesia, in which neuronal firing rates and network connectivity might change dramatically. A hierarchical Bayesian modeling approach combined with a variational Bayes (VB) algorithm is used for statistical inference. The effectiveness of our approach is evaluated with synthetic spike train data drawn from small and medium-size networks (consisting of up to 200 neurons), which are simulated using biophysical voltage-gated conductance models. We further apply the analysis to experimental spike train data recorded from rats' barrel cortex during both active behavior and isoflurane anesthesia conditions. Our results suggest that that neuronal interactions of both putative excitatory and inhibitory connections are reduced after the induction of isoflurane anesthesia.National Institutes of Health (U.S.) (NIH Grants DP1-OD003646

A PK–PD model of ketamine-induced high-frequency oscillations

Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic–pharmacodynamics (PK–PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK–PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK–PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent range of effects that ketamine has.National Institutes of Health (U.S.) (Pioneer Award DP1-OD003646)Burroughs Wellcome Fund (Career Award at the Scientific Interface)National Institutes of Health (U.S.) (Grant 5R01MH061976)National Institutes of Health (U.S.) (New Innovator Award DP2-OD006454

A new lower limb portable exoskeleton for gait assistance in neurological patients: a proof of concept study

Background: Few portable exoskeletons following the assist-as-needed concept have been developed for patients with neurological disorders. Thus, the main objectives of this proof-of-concept study were 1) to explore the safety and feasibility of an exoskeleton for gait rehabilitation in stroke and multiple sclerosis patients, 2) to test different algorithms for gait assistance and measure the resulting gait changes and 3) to evaluate the user's perception of the device. Methods: A cross-sectional study was conducted. Five patients were recruited (4 patients with stroke and 1 with multiple sclerosis). A robotic, one-degree-of-freedom, portable lower limb exoskeleton known as the Marsi Active Knee (MAK) was designed. Three control modes (the Zero Force Control mode, Mode 1 and Mode 3) were implemented. Spatiotemporal gait parameters were measured by the 10-m walking test (10MWT), the Gait Assessment and Intervention Tool (G.A.I.T.) and Tinetti Performance Oriented Mobility Assessment (gait subscale) before and after the trials. A modified QUEST 2.0 questionnaire was administered to determine each participant's opinion about the exoskeleton. The data acquired by the MAK sensors were normalized to a gait cycle, and adverse effects were recorded. Results: The MAK exoskeleton was used successfully without any adverse effects. Better outcomes were obtained in the 10MWT and G.A.I.T. when Mode 3 was applied compared with not wearing the device at all. In 2 participants, Mode 3 worsened the results. Additionally, Mode 3 seemed to improve the 10MWT and G.A.I.T. outcomes to a greater extent than Mode 1. The overall score for the user perception of the device was 2.8 ± 0.4 95% CI. Conclusions: The MAK exoskeleton seems to afford positive preliminary results regarding safety, feasibility, and user acceptance. The efficacy of the MAK should be studied in future studies, and more advanced improvements in safety must be implemented.G. Puyuelo-Quintana has received financial support by the “Doctorado Industrial” grant of Ministerio de Ciencia, Innovación y Universidades de España (reference DI-16- 08731). A. Plaza-Flores and E. Garces-Castellote have received financial support by the “Doctorado Industrial” grant of Comunidad de Madrid (reference IND2017/TIC-7698 and IND2018/TIC-9618, respectively).Peer reviewe

Genetic signatures of parental contribution in black and white populations in Brazil

Two hundred and three individuals classified as white were tested for 11 single nucleotide polymorphisms plus two insertion/deletions in their Y-chromosomes. A subset of these individuals (n = 172) was also screened for sequences in the first hypervariable segment of their mitochondrial DNA (mtDNA). In addition, complementary studies were done for 11 of the 13 markers indicated above in 54 of 107 black subjects previously investigated in this southern Brazilian population. The prevalence of Y-chromosome haplogroups among whites was similar to that found in the Azores (Portugal) or Spain, but not to that of other European countries. About half of the European or African mtDNA haplogroups of these individuals were related to their places of origin, but not their Amerindian counterparts. Persons classified in these two categories of skin color and related morphological traits showed distinct genomic ancestries through the country. These findings emphasize the need to consider in Brazil, despite some general trends, a notable heterogeneity in the pattern of admixture dynamics within and between populations/groups

SUPLEMENTO DEL XV CONGRESO INTERNACIONAL DE ACTIVIDAD FÍSICA Y DEPORTE. 17,18 y 19 DE OCTUBRE DEL 2018. ENSENADA, BAJA CALIFORNIA, MÉXICO

Compendio, en formato artículo, de los mejores trabajos presentados en el XV CONGRESO INTERNACIONAL DE ACTIVIDAD FÍSICA Y DEPORTE celebrado los días  17,18 y 19 de octubre del 2018 en la Universidad Autónoma de Baja California en la ciudad de Ensenada, Baja California, México:La nutrición en la actividad física y deportiva: alimentos funcionales con nanotecnología, aplicaciones potenciales. González González, K.Y.; Huerta Plaza, B.A.; Amaya Parra, G. (118-130)Perfil antropométrico, físico y hábitos alimentarios en escolares indígenas de Tijuana México. Avendaño Cano, D.L.; Gómez Miranda, L.M.; Aburto Corona, J.A. (131-142)Relación entre el clima de aprendizaje en Educación Física y la percepción de los estudiantes en las competencias del profesorado. Baños, R; Ortiz-Camacho, M.M.; Baena-Extremera, A.; Granero-Gallegos, A.; Machado-Parra, J.P.; Rentería, I.; Acosta, I.; Ramírez, L. (143-153)Valoración de capacidades físicas, composición corporal y consumo de vitaminas en una competencia de Crossfit. Cervantes-Hernández, N.; Hernández Nájera, N.; Carrasco Legleu, C.E.; Candia Lujan, R.; Enríquez Del Castillo, L.A. (154-164)Relación de la actividad física, características antropométricas y VO2máx en jóvenes universitarios: características por género. Enríquez-del Castillo, L.A.; Cervantes-Hernández, N.; Carrasco-Legleu, C.E.; Candia Luján, R. (165-174)Entrenamiento vibratorio de cuerpo completo y sus efectos sobre la composición corporal en jóvenes universitarios. Flores-Chico, B.; Bañuelos-Teres, L.E.; Buendía Lozada, E.R.P. (175-183)Actualización curricular, plan 2016 de la Licenciatura en Cultura Física de la BUAP. Flores-Chico, B.; Flores-Flores, A.; López de La Rosa, LE.; Aguilar-Enríquez, R.I.; Caballero Gómez, JM; Villanueva-Huerta, JA. (184-192)Evaluación psicológica y de la musculatura isquiosural de basquetbolistas universitarias en distintas etapas deportivas. Moranchel-Charros, R.; Martínez-Velázquez, E.S. (193-203)Efecto del ejercicio físico sobre la fuerza, resistencia y riesgo de caída en mujeres adultas. Ortiz Ortiz, M; Espinoza Gutiérrez, R; Gómez Miranda, LM.; Guzmán Gutiérrez, EC.; Calleja Núñez, JJ. (204-212)Desigualdad vs igualdad numérica y su efecto en la técnica de jugadores de fútbol infantil. Vega-Orozco, SI; Gavotto Nogales, OI; Bernal Reyes, F; Horta Gim, MA; Sarabia Sainz, HM. (213-224

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

7th Drug hypersensitivity meeting: part two

No abstract availabl

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years