Analiza stężenia wybranych neuroprzekaźników w surowicy chorych z zespołem Tourette'a

Background and purpose Metabolic disturbances of excitatory and inhibitory neurotransmitters are implicated in pathogenesis of Tourette syndrome (TS). The aim of the study was to measure serum concentrations of glutamic acid, γ-aminobutyric acid (GABA) and glycine in TS patients and evaluate any correlation between neurotransmitter levels and age at onset, actual age, gender, tic severity, duration of the disease and concomitant psychiatric disorders. Material and methods Sixty-seven TS patients, aged 16–59, and 57 healthy controls, aged 19–37, were enrolled in the study. Information regarding medical history and physical investigation was collected using a short questionnaire. Sixty-seven percent of patients were medication-free at the time of examination and the rest had withheld treatment for 24 hours before. Blood samples were taken after a 12-hour fasting period. HPLC technique was used. Results The TS group had higher glutamic acid and lower GABA levels. Glycine concentrations were comparable. No differences regarding neurotransmitter concentrations between treated and non-treated patients were found. Patients with concomitant obsessive-compulsive disorder and severe tics had higher glutamate levels. Glutamate concentrations correlated positively with the number of comorbid psychiatric disorders and GABA concentrations correlated negatively with the number of behavioural problems in patients with comorbidities. There was no correlation between analysed neurochemicals and age, gender, age at onset or disease duration. Conclusions Imbalance between excitatory and inhibitory systems in the brains of TS patients may be reflected by glutamate and GABA serum level changes. Glutamate and GABA may be biomarkers of the disease and high concentration of glutamate may indicate more severe course of TS.Wstęp i cel pracy Zaburzenia metabolizmu neuroprzekaźników pobudzających i hamujących odgrywają rolę w patogenezie zespołu Tourette'a. Celem pracy była analiza stężenia kwasu glutaminowego, γ-aminomasłowego (GABA) i glicyny w surowicy chorych z zespołem Tourette'a oraz ocena zależności pomiędzy stężeniami neurotransmiterów a wiekiem lub płcią, wiekiem w chwili zachorowania, nasileniem tików, czasem trwania choroby i współistniejącymi zaburzeniami psychiatrycznymi. Materiał i metody Zbadano 67 chorych na zespół Tourette'a w wieku 16–59 lat oraz 57 zdrowych osób w wieku 19–37 lat. Wykorzystano ankietę obejmującą informacje z badania podmiotowego i przedmiotowego. Sześćdziesiąt siedem procent chorych nie przyjmowało żadnych leków w momencie badania, u pozostałych wstrzymano podawanie 24 godziny przed pobraniem krwi. Próbki zebrano po 12-godzinnym okresie na czczo. Oznaczeń dokonano metodą HPLC. Wyniki W grupie chorych stężenie kwasu glutaminowego było większe, zaś GABA – mniejsze. Stężenie glicyny było podobne. Nie stwierdzono istotnej różnicy stężeń neuroprzekaźników pomiędzy grupą osób leczonych i nieleczonych. W grupie osób ze współistniejącym zaburzeniem obsesyjno–kompulsywnym oraz ciężkim nasileniem tików stężenie kwasu glutaminowego było większe. Stwierdzono dodatnią korelację pomiędzy stężeniem kwasu glutaminowego a liczbą dodatkowych zaburzeń psychiatrycznych oraz odwrotną kore-lację pomiędzy stężeniem GABA a liczbą zaburzeń behawioralnych w grupie ze współistniejącymi zaburzeniami psychiatrycznymi. Nie stwierdzono korelacji pomiędzy stężeniami analizowanych neuroprzekaźników a wiekiem lub płcią pacjentów, wiekiem zachorowania ani czasem trwania choroby. Wnioski Zaburzenie równowagi pomiędzy układem pobudzającym i hamującym w mózgu chorych z zespołem Tourette'a może się manifestować zmianami stężeń kwasu glutaminowego i GABA w surowicy. Kwas glutaminowy i GABA mogą być markerami choroby, a duże stężenie glutaminianu we krwi chorych może oznaczać cięższy przebieg zespołu Tourette'a

Safety and Effectiveness of Vibration Massage by Deep Oscillations: A Prospective Observational Study

The objective of this study is to assess the safety of treatment with vibration massage using a deep oscillation device and the effects on symptom severity and quality of life in patients with primary fibromyalgia syndrome (FMS). Outpatients with FMS performed an observational prospective study with visits 2–4 weeks after the last treatment (control) and after further 2 months (follow-up). Patients were treated with 10 sessions of 45 min deep oscillation massage, 2/week. Primary outcome parameters were safety and tolerability (5-level Likert scale (1 = very good)) (after each treatment session and at control visit). Secondary outcome parameters were symptom severity (Fibromyalgia Impact Questionnaire (FIQ), pain) and quality of life (SF-36). Seventy patients (97.1% females) were included. At control visit, 41 patients (58.6%) reported 63 mild and short-lasting adverse events, mainly worsening of prevalent symptoms such as pain and fatigue. Tolerability was rated as 1.8 (95% confidence interval: 1.53; 2.07). Symptoms and quality of life were significantly improved at both control and follow-up visits (at least P<0.01). In conclusion, deep oscillation massage is safe and well tolerated in patients with FMS and might improve symptoms and quality of life rather sustained

Relationships between External, Wearable Sensor-Based, and Internal Parameters: A Systematic Review

Micro electro-mechanical systems (MEMS) are used to record training and match play of intermittent team sport athletes. Paired with estimates of internal responses or adaptations to exercise, practitioners gain insight into players’ dose–response relationship which facilitates the prescription of the training stimuli to optimize performance, prevent injuries, and to guide rehabilitation processes. A systematic review on the relationship between external, wearable-based, and internal parameters in team sport athletes, compliant with the PRISMA guidelines, was conducted. The literature research was performed from earliest record to 1 September 2020 using the databases PubMed, Web of Science, CINAHL, and SportDISCUS. A total of 66 full-text articles were reviewed encompassing 1541 athletes. About 109 different relationships between variables have been reviewed. The most investigated relationship across sports was found between (session) rating of perceived exertion ((session-)RPE) and PlayerLoad™ (PL) with, predominantly, moderate to strong associations (r = 0.49–0.84). Relationships between internal parameters and highly dynamic, anaerobic movements were heterogenous. Relationships between average heart rate (HR), Edward’s and Banister’s training impulse (TRIMP) seem to be reflected in parameters of overall activity such as PL and TD for running-intensive team sports. PL may further be suitable to estimate the overall subjective perception. To identify high fine-structured loading—relative to a certain type of sport—more specific measures and devices are needed. Individualization of parameters could be helpful to enhance practicality

Behavioral responses of terrestrial mammals to COVID-19 lockdowns

DATA AND MATERIALS AVAILABILITY : The full dataset used in the final analyses (33) and associated code (34) are available at Dryad. A subset of the spatial coordinate datasets is available at Zenodo (35). Certain datasets of spatial coordinates will be available only through requests made to the authors due to conservation and Indigenous sovereignty concerns (see table S1 for more information on data use restrictions and contact information for data requests). These sensitive data will be made available upon request to qualified researchers for research purposes, provided that the data use will not threaten the study populations, such as by distribution or publication of the coordinates or detailed maps. Some datasets, such as those overseen by government agencies, have additional legal restrictions on data sharing, and researchers may need to formally apply for data access. Collaborations with data holders are generally encouraged, and in cases where data are held by Indigenous groups or institutions from regions that are under-represented in the global science community, collaboration may be required to ensure inclusion.COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals’ 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.The Radboud Excellence Initiative, the German Federal Ministry of Education and Research, the National Science Foundation, Serbian Ministry of Education, Science and Technological Development, Dutch Research Council NWO program “Advanced Instrumentation for Wildlife Protection”, Fondation Segré, RZSS, IPE, Greensboro Science Center, Houston Zoo, Jacksonville Zoo and Gardens, Nashville Zoo, Naples Zoo, Reid Park Zoo, Miller Park, WWF, ZCOG, Zoo Miami, Zoo Miami Foundation, Beauval Nature, Greenville Zoo, Riverbanks zoo and garden, SAC Zoo, La Passarelle Conservation, Parc Animalier d’Auvergne, Disney Conservation Fund, Fresno Chaffee zoo, Play for nature, North Florida Wildlife Center, Abilene Zoo, a Liber Ero Fellowship, the Fish and Wildlife Compensation Program, Habitat Conservation Trust Foundation, Teck Coal, and the Grand Teton Association. The collection of Norwegian moose data was funded by the Norwegian Environment Agency, the German Ministry of Education and Research via the SPACES II project ORYCS, the Wyoming Game and Fish Department, Wyoming Game and Fish Commission, Bureau of Land Management, Muley Fanatic Foundation (including Southwest, Kemmerer, Upper Green, and Blue Ridge Chapters), Boone and Crockett Club, Wyoming Wildlife and Natural Resources Trust, Knobloch Family Foundation, Wyoming Animal Damage Management Board, Wyoming Governor’s Big Game License Coalition, Bowhunters of Wyoming, Wyoming Outfitters and Guides Association, Pope and Young Club, US Forest Service, US Fish and Wildlife Service, the Rocky Mountain Elk Foundation, Wyoming Wild Sheep Foundation, Wild Sheep Foundation, Wyoming Wildlife/Livestock Disease Research Partnership, the US National Science Foundation [IOS-1656642 and IOS-1656527, the Spanish Ministry of Economy, Industry and Competitiveness, and by a GRUPIN research grant from the Regional Government of Asturias, Sigrid Rausing Trust, Batubay Özkan, Barbara Watkins, NSERC Discovery Grant, the Federal Aid in Wildlife Restoration act under Pittman-Robertson project, the State University of New York, College of Environmental Science and Forestry, the Ministry of Education, Youth and Sport of the Czech Republic, the Ministry of Agriculture of the Czech Republic, Rufford Foundation, an American Society of Mammalogists African Graduate Student Research Fund, the German Science Foundation, the Israeli Science Foundation, the BSF-NSF, the Ministry of Agriculture, Forestry and Food and Slovenian Research Agency (CRP V1-1626), the Aage V. Jensen Naturfond (project: Kronvildt - viden, værdier og værktøjer), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy, National Centre for Research and Development in Poland, the Slovenian Research Agency, the David Shepherd Wildlife Foundation, Disney Conservation Fund, Whitley Fund for Nature, Acton Family Giving, Zoo Basel, Columbus, Bioparc de Doué-la-Fontaine, Zoo Dresden, Zoo Idaho, Kolmården Zoo, Korkeasaari Zoo, La Passarelle, Zoo New England, Tierpark Berlin, Tulsa Zoo, the Ministry of Environment and Tourism, Government of Mongolia, the Mongolian Academy of Sciences, the Federal Aid in Wildlife Restoration act and the Illinois Department of Natural Resources, the National Science Foundation, Parks Canada, Natural Sciences and Engineering Research Council, Alberta Environment and Parks, Rocky Mountain Elk Foundation, Safari Club International and Alberta Conservation Association, the Consejo Nacional de Ciencias y Tecnología (CONACYT) of Paraguay, the Norwegian Environment Agency and the Swedish Environmental Protection Agency, EU funded Interreg SI-HR 410 Carnivora Dinarica project, Paklenica and Plitvice Lakes National Parks, UK Wolf Conservation Trust, EURONATUR and Bernd Thies Foundation, the Messerli Foundation in Switzerland and WWF Germany, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions, NASA Ecological Forecasting Program, the Ecotone Telemetry company, the French National Research Agency, LANDTHIRST, grant REPOS awarded by the i-Site MUSE thanks to the “Investissements d’avenir” program, the ANR Mov-It project, the USDA Hatch Act Formula Funding, the Fondation Segre and North American and European Zoos listed at http://www.giantanteater.org/, the Utah Division of Wildlife Resources, the Yellowstone Forever and the National Park Service, Missouri Department of Conservation, Federal Aid in Wildlife Restoration Grant, and State University of New York, various donors to the Botswana Predator Conservation Program, data from collared caribou in the Northwest Territories were made available through funds from the Department of Environment and Natural Resources, Government of the Northwest Territories. The European Research Council Horizon2020, the British Ecological Society, the Paul Jones Family Trust, and the Lord Kelvin Adam Smith fund, the Tanzania Wildlife Research Institute and Tanzania National Parks. The Eastern Shoshone and Northern Arapahoe Fish and Game Department and the Wyoming State Veterinary Laboratory, the Alaska Department of Fish and Game, Kodiak Brown Bear Trust, Rocky Mountain Elk Foundation, Koniag Native Corporation, Old Harbor Native Corporation, Afognak Native Corporation, Ouzinkie Native Corporation, Natives of Kodiak Native Corporation and the State University of New York, College of Environmental Science and Forestry, and the Slovenia Hunters Association and Slovenia Forest Service. F.C. was partly supported by the Resident Visiting Researcher Fellowship, IMéRA/Aix-Marseille Université, Marseille. This work was partially funded by the Center of Advanced Systems Understanding (CASUS), which is financed by Germany’s Federal Ministry of Education and Research (BMBF) and by the Saxon Ministry for Science, Culture and Tourism (SMWK) with tax funds on the basis of the budget approved by the Saxon State Parliament. This article is a contribution of the COVID-19 Bio-Logging Initiative, which is funded in part by the Gordon and Betty Moore Foundation (GBMF9881) and the National Geographic Society.https://www.science.org/journal/sciencehj2023Mammal Research InstituteZoology and Entomolog

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Relationships between External, Wearable Sensor-Based, and Internal Parameters: A Systematic Review

Micro electro-mechanical systems (MEMS) are used to record training and match play of intermittent team sport athletes. Paired with estimates of internal responses or adaptations to exercise, practitioners gain insight into players’ dose–response relationship which facilitates the prescription of the training stimuli to optimize performance, prevent injuries, and to guide rehabilitation processes. A systematic review on the relationship between external, wearable-based, and internal parameters in team sport athletes, compliant with the PRISMA guidelines, was conducted. The literature research was performed from earliest record to 1 September 2020 using the databases PubMed, Web of Science, CINAHL, and SportDISCUS. A total of 66 full-text articles were reviewed encompassing 1541 athletes. About 109 different relationships between variables have been reviewed. The most investigated relationship across sports was found between (session) rating of perceived exertion ((session-)RPE) and PlayerLoad™ (PL) with, predominantly, moderate to strong associations (r = 0.49–0.84). Relationships between internal parameters and highly dynamic, anaerobic movements were heterogenous. Relationships between average heart rate (HR), Edward’s and Banister’s training impulse (TRIMP) seem to be reflected in parameters of overall activity such as PL and TD for running-intensive team sports. PL may further be suitable to estimate the overall subjective perception. To identify high fine-structured loading—relative to a certain type of sport—more specific measures and devices are needed. Individualization of parameters could be helpful to enhance practicality

EREC-II in use - studies on usability and suitability of a sensor system for affect detection and human performance monitoring

Interest in emotion detection is increasing significantly. For research and development in the field of Affective Computing, in smart environments, but also for reliable non-lab medical and psychological studies or human performance monitoring, robust technologies are needed for detecting evidence of emotions in persons under everyday conditions. This paper reports on evaluation studies of the EREC-II sensor system for acquisition of emotionrelated physiological parameters. The system has been developed with a focus on easy handling, robustness, and reliability. Two sets of studies have been performed covering 4 different application fields: medical, human performance in sports, driver assistance, and multimodal affect sensing. Results show that the different application fields pose different requirements mainly on the user interface, while the hardware for sensing and processing the data proved to be in an acceptable state for use in different research domains