A novel martial arts-based virtuality reality intervention modulates pain and the pain neuromatrix in patients with opioid use disorder

Background: Standard-of-care for opioid use disorder (OUD) includes medication and counseling. However, there is an unmet need for complementary approaches to treat OUD patients coping with pain; furthermore, few studies have probed neurobiological features of pain or its management during OUD treatment. This preliminary study examines neurobiological and behavioral effects of a martial arts-based intervention in patients undergoing methadone maintenance treatment (MMT). Methods: Fifteen (11 female) MMT patients completed a virtual reality, therapist-guided martial arts intervention that included breathing and relaxation exercises; sessions were scheduled twice weekly. Assessments included functional magnetic resonance imaging (fMRI) of pain neuromatrix activation and connectivity (pre- and post-intervention), saliva cortisol and C-reactive protein (CRP) at baseline and weeks 4, 8 and 12; and self-reported pain and affective symptoms before and after each intervention session. Results: After each intervention session (relative to pre-session), ratings of pain, opioid craving, anxiety and depression (but not anger) decreased. Saliva cortisol (but not CRP) levels decreased from pre- to post-session. From pre- to post-intervention fMRI assessments, pain task-related left postcentral gyrus (PCG) activation decreased. Higher baseline cortisol levels were associated with greater post-intervention pain task-related insular activation. At baseline, PCG showed positive connectivity with other regions of the pain neuromatrix, but this pattern changed post-intervention. Conclusions: These preliminary findings demonstrate feasibility, therapeutic promise, and brain basis of a martial arts-based intervention for OUD patients undergoing MMT

Вимоги видавничого відділу ІМФЕ ім. М. Т. Рильського до оформлення авторами рукописів

Industrial parts are manufactured to tolerances as no production process is capable of delivering perfectly identical parts. It is unacceptable that a plan for a manipulation task that was determined on the basis of a CAD model of a part fails on some manufactured instance of that part, and therefore it is crucial that the admitted shape variations are systematically taken into account during the planning of the task. We study the problem of orienting a part with given admitted shape variations by means of pushing with a single frictionless jaw. We use a very general model for admitted shape variations that only requires that any valid instance must contain a given convex polygon PI while it must be contained in another convex polygon PE. The problem that we solve is to determine, for a given h, the sequence of h push actions that puts all valid instances of a part with given shape variation into the smallest possible interval of final orientations. The resulting algorithm runs in O(hn) time, where n=|PI|+|PE|

Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony.

: Plasmodium parasites, the causative agents of malaria, have evolved a unique cell division cycle in the clinically relevant asexual blood stage of infection(1). DNA replication commences approximately halfway through the intracellular development following invasion and parasite growth. The schizont stage is associated with multiple rounds of DNA replication and nuclear division without cytokinesis, resulting in a multinucleated cell. Nuclei divide asynchronously through schizogony, with only the final round of DNA replication and segregation being synchronous and coordinated with daughter cell assembly(2,3). However, the control mechanisms for this divergent mode of replication are unknown. Here, we show that the Plasmodium-specific kinase PfCRK4 is a key cell-cycle regulator that orchestrates multiple rounds of DNA replication throughout schizogony in Plasmodium falciparum. PfCRK4 depletion led to a complete block in nuclear division and profoundly inhibited DNA replication. Quantitative phosphoproteomic profiling identified a set of PfCRK4-regulated phosphoproteins with greatest functional similarity to CDK2 substrates, particularly proteins involved in the origin of replication firing. PfCRK4 was required for initial and subsequent rounds of DNA replication during schizogony and, in addition, was essential for development in the mosquito vector. Our results identified an essential S-phase promoting factor of the unconventional P. falciparum cell cycle. PfCRK4 is required for both a prolonged period of the intraerythrocytic stage of Plasmodium infection, as well as for transmission, revealing a broad window for PfCRK4-targeted chemotherapeutics.<br/

Using genetic algorithms to generate test sequences for complex timed systems

The generation of test data for state based specifications is a computationally expensive process. This problem is magnified if we consider that time con- straints have to be taken into account to govern the transitions of the studied system. The main goal of this paper is to introduce a complete methodology, sup- ported by tools, that addresses this issue by represent- ing the test data generation problem as an optimisa- tion problem. We use heuristics to generate test cases. In order to assess the suitability of our approach we consider two different case studies: a communication protocol and the scientific application BIPS3D. We give details concerning how the test case generation problem can be presented as a search problem and automated. Genetic algorithms (GAs) and random search are used to generate test data and evaluate the approach. GAs outperform random search and seem to scale well as the problem size increases. It is worth to mention that we use a very simple fitness function that can be eas- ily adapted to be used with other evolutionary search techniques

Particle swarm optimization with sequential niche technique for dynamic finite element model updating

Peer reviewedPostprin

Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery

BACKGROUND: Renal impairment is one of the predictors of mortality in cardiac surgery. Usually a binarized value of serum creatinine is used to assess the renal function in risk models. Creatinine clearance can be easily estimated by the Cockcroft and Gault equation from serum creatinine, gender, age and body weight. In this work we examine whether this estimation of the glomerular filtration rate can advantageously replace the serum creatinine in the EuroSCORE preoperative risk assessment. METHODS: In a group of 8138 patients out of a total of 11878 patients, who underwent cardiac surgery in our hospital between January 1996 and July 2002, the 18 standard EuroSCORE parameters could retrospectively be determined and logistic regression analysis performed. In all patients scored, creatinine clearance was calculated according to Cockcroft and Gault. The relationship between the predicted and observed 30-days mortality was evaluated in systematically selected intervals of creatinine clearance and significance values computed by employing Monte Carlo methods. Afterwards, risk scoring was performed using a continuous or a categorical value of creatinine clearance instead of serum creatinine. The predictive ability of several risk score models and the individual contribution of their predictor variables were studied using ROC curve analysis. RESULTS: The comparison between the expected and observed 30-days mortalities, which were determined in different intervals of creatinine clearance, revealed the best threshold value of 55 ml/min. A significantly higher 30-days mortality was observed below this threshold and vice versa (both with p < 0.001). The local adaptation of the EuroSCORE is better than the standard EuroSCORE and was further improved by replacing serum creatinine (SC) by creatinine clearance (CC). Differential ROC analysis revealed that CC is superior to SC in providing predictive power within the logistic regression. Variable rank comparison identified CC as the best single variable predictor, even better than the variable age, former number 1, and SC, previously number 9 in the standard set of EuroSCORE variables. CONCLUSION: The renal function is an important determinant of mortality in heart surgery. This risk factor is not well captured in the standard EuroSCORE risk evaluation system. Our study shows that creatinine clearance, calculated according to the Cockcroft and Gault equation, should be applied to estimate the preoperative renal function instead of serum creatinine. This predictor variable replacement gains a significant improvement in the predictive accuracy of the scoring model

Contribution of Direct Heating, Thermal Conduction and Perfusion During Radiofrequency and Microwave Ablation

Both radiofrequency (RF) and microwave (MW) ablation devices are clinically used for tumor ablation. Several studies report less dependence on vascular mediated cooling of MW compared to RF ablation. We created computer models of a cooled RF needle electrode, and a dipole MW antenna to determine differences in tissue heat transfer

A Systematic Review of Music Therapy Practice and Outcomes with Acute Adult Psychiatric In-Patients

PMCID: PMC3732280This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Born to yawn? Understanding yawning as a warning of the rise in cortisol levels: Randomized trial

Background: Yawning consistently poses a conundrum to the medical profession and neuroscientists. Despite neurological evidence such as parakinesia brachialis oscitans in stroke patients and thermo-irregulation in multiple sclerosis patients, there is considerable debate over the reasons for yawning with the mechanisms and hormonal pathways still not fully understood. Cortisol is implicated during yawning and may link many neurological disorders. Evidence was found in support of the Thompson cortisol hypothesis that proposes cortisol levels are elevated during yawning just as they tend to rise during stress and fatigue. Objectives: To investigate whether saliva cortisol levels rise during yawning and, therefore, support the Thompson cortisol hypothesis. Methods: We exposed 20 male and female volunteers aged between 18 and 53 years to conditions that provoked a yawning response in a randomized controlled trial. Saliva samples were collected at the start and again after the yawning response, or at the end of the stimuli presentations if the participant did not yawn. In addition, we collected electromyographic data of the jaw muscles to determine rest and yawning phases of neural activity. Yawning susceptibility scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, and demographic and health details were also collected from each participant. A comprehensive data set allowed comparison between yawners and nonyawners, as well as between rest and yawning phases. Collecting electromyographic data from the yawning phase is novel, and we hope this will provide new information about neuromuscular activity related to cortisol levels. Exclusion criteria included chronic fatigue, diabetes, fibromyalgia, heart conditions, high blood pressure, hormone replacement therapy, multiple sclerosis, and stroke. We compared data between and within participants. Results: In the yawning group, there was a significant difference between saliva cortisol samples (t = -3.071, P = .01). Power and effect size were computed based on repeated-measures t tests for both the yawning and nonyawning groups. There was a medium effect size for the nonyawners group (r = .467) but low power (36%). Results were similar for the yawners group: medium effect size (r = .440) and low power (33%). Conclusions: There was significant evidence in support of the Thompson cortisol hypothesis that suggests cortisol levels are elevated during yawning. A further longitudinal study is planned to test neurological patients. We intend to devise a diagnostic tool based on changes in cortisol levels that may assist in the early diagnosis of neurological disorders based on the data collected. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 61942768; http://www.controlled-trials.com/ISRCTN61942768/61942768 (Archived by WebCite at http://www.webcitation.org/6A75ZNYvr)

Characteristics of the Early Immune Response Following Transplantation of Mouse ES Cell Derived Insulin-Producing Cell Clusters

Background The fully differentiated progeny of ES cells (ESC) may eventually be used for cell replacement therapy (CRT). However, elements of the innate immune system may contribute to damage or destruction of these tissues when transplanted. Methodology/Principal Findings Herein, we assessed the hitherto ill-defined contribution of the early innate immune response in CRT after transplantation of either ESC derived insulin producing cell clusters (IPCCs) or adult pancreatic islets. Ingress of neutrophil or macrophage cells was noted immediately at the site of IPCC transplantation, but this infiltration was attenuated by day three. Gene profiling identified specific inflammatory cytokines and chemokines that were either absent or sharply reduced by three days after IPCC transplantation. Thus, IPCC transplantation provoked less of an early immune response than pancreatic islet transplantation. Conclusions/Significance Our study offers insights into the characteristics of the immune response of an ESC derived tissue in the incipient stages following transplantation and suggests potential strategies to inhibit cell damage to ensure their long-term perpetuation and functionality in CRT