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This work presents a measurement for the identification of translational quasi-static stiffness of machine tool using Stiffness Workspace System (SWS). The novelty of this work is a significant modification of the SWS. The changes in measurement procedure and data analysis as well as new technical solutions are described in detail. A methodology for generalised translational static stiffness determination is presented. The major purpose of this paper is to provide the information about quasi-static stiffness values that characterise a typical machine tool. The measurement procedure is implemented in a case study on a 5-axis machining centre. Measurement results were used to determine the generalised translational stiffness indicators of points in the workspace. Then, the static stiffness distribution on the XY plane over machining space was estimated. The obtained results confirm the importance of analyses of static stiffness distribution as they point out areas where some possible changes occur. In the conclusion of the paper the utility value of the information of translational static stiffness is emphasised.

Background Epidemiological data indicate a high rate of comorbidity of depression and cocaine use disorder (CUD). The role of serotonin 2C (5-HT2C) receptors in the mechanisms responsible for the coexistence of depression and CUD was not investigated. Methods We combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in male rats to investigate two 5-HT2C receptor agonists (Ro 60-0175 (RO) and WAY 161503 (WAY)) and the 5-HT2C-receptor preferring antagonist mirtazapine (MIR; an antidepressant), with the goal of determining whether these drugs alter cocaine-induced reinforcement and seeking behaviors. Additionally, neurochemical analyses were performed following cocaine self-administration and its abstinence period in the brain structures in OBX rats and SHAM-operated controls. Results Acute administration of RO reduced, while WAY non-significantly attenuated cocaine reinforcement in both rat phenotypes. Moreover, RO or WAY protected against cocaine-seeking behavior after acute or after repeated drug administration during extinction training in OBX and SHAM rats. By contrast, acutely administered MIR did not alter cocaine reinforcement in both rat phenotypes, while it’s acute (but not repeated) pretreatment reduced cocaine-seeking in OBX and SHAM rats. In neurochemical analyses, cocaine reinforcement increased 5-HT2C receptor levels in the ventral hippocampus; a preexisting depression-like phenotype enhanced this effect. The 10-daily cocaine abstinence reduced 5-HT2C receptor expression in the dorsolateral striatum, while the coexistence of depression and CUD enhanced local receptor expression. Conclusion The results support a key role of 5-HT2C receptors for treating CUD and comorbid depression and CUD. They may be backs the further research of pharmacological strategies with drug targeting receptors. Graphical abstract

Epidemiological data indicate a high rate of comorbidity of depression and cocaine use disorder (CUD). The role of 5-HT2C receptors in the mechanisms responsible for the coexistence of CUD and depression has not been investigated. Here, we combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in male rats to investigate two 5-HT2C receptor agonists (Ro 60–0175 (RO) and WAY 161503 (WAY)) and the 5-HT2C-receptor preferring antagonist mirtazapine (MIR; an antidepressant), with the goal of determining whether these drugs alter cocaine-induced reinforcement and seeking behaviors. Additionally, neurochemical analyses following cocaine self-administration and its abstinence period in the brain structures in OBX rats and SHAM-operated controls were performed.Acute administration of RO reduced, while WAY non-significantly attenuated cocaine reinforcement in OBX and SHAM rats. Moreover, RO or WAY protected against cocaine-seeking behavior after acute repeated drug administration during extinction training in OBX and SHAM rats. By contrast, acutely administered MIR did not alter cocaine reinforcement in both rat phenotypes, while acute (but not repeated) pretreatment reduced cocaine seeking in OBX and SHAM rats. In neurochemical analyses, cocaine reinforcement increased 5-HT2C receptor levels in the ventral hippocampus; this effect was enhanced by preexisting depression. The 10-daily cocaine abstinence from self-administration reduced 5-HT2C receptor expression in the dorsolateral striatum but coexistence of depression and CUD enhanced local receptor expression. The present study is an extra recommendation to support current development of pharmacological strategies with drugs targeting the 5-HT2C receptor for the treatment of comorbid depression and CUD.

Background: Myometrial invasion (MI) is a parameter currently used in transvaginal ultrasound (TVS) in endometrial cancer (EC) to determine local staging, however, without molecular diagnostics, it is insufficient for selection of high-risk cases, i.e., those with a high risk of lymph node metastases (LNM). Methods: One hundred sixteen consecutive EC patients, who had received 2D transvaginal ultrasound examinations in their preoperative workup and final histopathology results as a reference standard, were included in this prospective study. Univariate and multivariate logistic models of analyzed TVS biomarkers (tumor [T] size, T area [AREA], T volume [SPE-VOL], MI, T-free distance to serosa [TFD], endo-myometrial irregularity, [EMIR], cervical stromal involvement, CSI) were evaluated to assess the relative accuracy of the possible LNM predictors. To avoid a potential bias in assuming linear relations between LNM and continuous predictors, spline functions were applied. Calculations were made in R with the use of libraries splines, glmulti, and pROC. Results: LNM was found in 20 out of 116 (17%) patients. In univariate analysis, only uMI, EMIR, uCSI and uTFD were significant predictors of LNM. Accuracy was 0.707 (AUC 0.684, 95% CI 0.568-0.801) for uMI (p50%, and SPE-VOL for patients with uCSI, allows for the most accurate prediction of LNM in EC, rather than uMI alone.

Background Opioid use disorders are serious contributors to the harms associated with the drug use. Unfortunately, therapeutic interventions for opioid addicts after detoxification have been limited and not sufficiently effective. Recently, several studies have led to promising results with disulfiram (DSF), a dopamine β-hydroxylase (DBH) inhibitor, showing that it is a potent agent against not only alcohol but also addiction to various drugs. Materials and methods This study was designed to examine whether DSF and nepicastat (NEP; another DBH inhibitor) modify morphine intake and reinstatement of seeking-behavior using the rat model of intravenous morphine self-administration. Additionally, we intended to estimate the effects of both inhibitors on the locomotor activity as well as on extracellular dopamine and its metabolite levels in the nucleus accumbens using microdialysis in naive rats. Results We demonstrated that both DBH inhibitors reduced responding to morphine self-administration. Moreover, DSF and NEP administered acutely before reinstatement test sessions consistently attenuated the reinforcing effects of morphine and a morphine-associated conditioned cue. The observed effects for lower doses (6.25–25 mg/kg; ip) of both DBH inhibitors seem to be independent of locomotor activity reduction and dopamine level in the nucleus accumbens. Neither DSF nor NEP administered daily during morphine abstinence with extinction training sessions had any effect on active lever-responding and changed the reinstatement induced by morphine priming doses. Reinstatement of drug-seeking behavior induced by a conditioned cue previously associated with morphine delivery was attenuated following repeated administration of DSF or NEP during the abstinence period. Conclusion These results seem to point to the significance of DBH inhibition as a potential pharmacotherapy against morphine use disorders. Graphic abstract

This work presents a measurement for the identification of translational quasi-static stiffness of machine tool using Stiffness Workspace System (SWS). The novelty of this work is a significant modification of the SWS. The changes in measurement procedure and data analysis as well as new technical solutions are described in detail. A methodology for generalised translational static stiffness determination is presented. The major purpose of this paper is to provide the information about quasi-static stiffness values that characterise a typical machine tool. The measurement procedure is implemented in a case study on a 5-axis machining centre. Measurement results were used to determine the generalised translational stiffness indicators of points in the workspace. Then, the static stiffness distribution on the XY plane over machining space was estimated. The obtained results confirm the importance of analyses of static stiffness distribution as they point out areas where some possible changes occur. In the conclusion of the paper the utility value of the information of translational static stiffness is emphasized.

Celem badań własnych była ocena zjawiska absencji na lekcjach wychowania fizycznego u młodzieży uczęszczającej do liceum, z podziałem na płeć respondentów. Zastosowano metodę sondażu diagnostycznego, badaniami ankietowymi objęto 51 losowo wybranych uczniów w wieku 14‒18 lat łódzkiego liceum ogólnokształcącego. Wyniki badań poddano analizie statystycznej, oceniając istotność statystyczną różnic. Wyniki wskazują, iż dziewczęta rzadziej i niechętnie uczestniczą w lekcjach wychowania fizycznego w porównaniu z chłopcami. W mniejszym stopniu niż chłopcy mają świadomość korzyści płynących z aktywności fizycznej dla zdrowia oraz prawidłowego rozwoju organizmu.

Cytochrome P450 is responsible for the metabolism of endogenous substrates, drugs and substances of abuse. The brain and nervous system regulate liver cytochrome P450 via neuroendocrine mechanisms, as shown in rodents. Cocaine exerts its addictive effects through the dopaminergic system, the functioning of which undergoes changes during its continuous use. Therefore, it can be hypothesized that the regulation of cytochrome P450 by cocaine may also alter during the addiction process, cessation and relapse. We analyzed preclinical studies on the mechanisms of the pharmacological action of cocaine, the role of the brain’s dopaminergic system in the neuroendocrine regulation of cytochrome P450 and the in vitro and in vivo effects of cocaine on the cytochrome P450 expression/activity and hepatotoxicity. The results of passive cocaine administration indicate that cocaine affects liver cytochrome P450 enzymes (including those engaged in its own metabolism) via different mechanisms involving the expression of genes encoding cytochrome P450 enzymes and interaction with enzyme proteins. Thus, it may affect its own oxidative metabolism and the metabolism of endogenous substrates and other co-administered drugs and may lead to hepatotoxicity. Its effect depends on the specific cytochrome P450 enzyme affected, cocaine dosage, treatment duration and animal species. However, further complementary studies are needed to find out whether cocaine affects cytochrome P450 via the brain’s dopaminergic system. The knowledge of cocaine’s effect on cytochrome P450 function during the entire addiction process is still incomplete. There is a lack of information on the enzyme expression/activity in animals self-administering cocaine (addicted), in those withdrawn after cocaine self-administration, and during relapse in animals previously addicted; furthermore, there is no such information concerning humans. The subject of cytochrome P450 regulation by cocaine during the addiction process is an open issue, and addressing this topic may help in the treatment of drug abuse patients.

Background Physical inactivity is strongly associated with obesity, which in turn is a major risk factor for many non-communicable diseases. We examined associations between physical inactivity and obesity in Spanish adults with vision and hearing difficulties and explored differences between men and women. Methods Data from the Spanish National Health Survey 2017 were analyzed [n = 23 089 adults (15–103 years, mean age 53.4 ± 18.9 years, 45.9% men)]. Participants self-reported difficulties in seeing and hearing. Physical inactivity (exposure) was evaluated with the International Physical Activity Questionnaire Short Form. Obesity (outcome) was defined as body mass index ≥30 kg m−2 based on self-reported weight and height. The association between physical inactivity and obesity was assessed with multivariable logistic regression in people with difficulties seeing and hearing, adjusting for significant covariates. Results Multivariable logistic regression analyses showed that the association between physical inactivity and obesity was stronger in those with difficulty hearing (OR 1.778, 95% CI 1.215–2.602) compared with difficulty seeing (OR 1.375, 95% CI 1.076–1.756). Gender-stratified analyses showed significant association between physical inactivity and obesity in men who reported difficulty hearing (OR 2.319, 95% CI 1.441–3.735) and difficulty seeing (OR 1.556, 95% CI 1.079–2.244), but not in women. Conclusions A significant association between physical inactivity and obesity was observed in Spanish men with vision and hearing difficulties. Physical activity has an important role in the prevention of obesity in men with seeing and hearing difficulties. Active steps should be taken to encourage physical activity to reduce the risk of obesity in people with sensory impairments.

Muscle strength and maximal speed are factors determining athlete’s results during competition. Their association with ACTN3 gene activity has been documented. The purpose of this study was the analysis of ACTN3 gene expression during a 2 month training cycle of soccer players and its correlation with the countermovement jump (CMJ) and squat jump (SJ). The study group consisted of 22 soccer players (aged 17‐18). The study material included peripheral blood lymphocytes. The relative expression (RQ) of the ACTN3 gene was analyzed by qPCR and performed before and after the two‐month training cycle. Before the training cycle low expression levels of ACTN3 (median RQ = 0.95) were observed, yet after the training cycle they were elevated (median RQ = 1.98) ( p = 0.003). There was an increase in performance of both jumps: SJ (p = 0.020) and CMJ (p = 0.012) at the end of the training cycle. A simultaneous increase in the ACTN3 gene expression level and height in both jump tests was observed in 73% of athletes (p > 0.05). There were no significant relationships between the ACTN3 gene expression level and the results of the CMJ and SJ. However, explosive strength is a complex feature shaped by many different factors and it could be the reason why we did not observe correlations between these variables.

After many years of intensive work the international experts from ISO TC 39 published the technical report called ISO TR 16907 “Machine tools – numerical compensation of geometric errors”. This document defines the terminology, presents benefits and limitations of numerical compensation of machine tools’ and measuring machines’ errors. It gives machines manufacturers and users vital information about how to use numerical compensation. In the context of those types of compensation defined in ISO TR 16907, this article shows rules of selecting models of Volumetric Error for three-axis machine tools. What is more, this paper presents some principles of reduction of these proposed models because of the functional tasks for machine tools. One of the obtained results is an array of reduced models for three-axis machine tools. This array determines the degree of detail of the model and the experimental research program that needs to be carried out in order to determine the Volumetric Error distribution.

After many years of intensive work, experts from ISO TC 39 have published the technical report ISO TR 16907 “Machine tools – numerical compensation of geometric errors”. This document defines the terminology, presents advantages and limitations of numerical compensation of machine tool and measuring machine. This gives machine manufacturers and users important information on the application of numerical compensation. In the context of the compensation types defined in ISO TR 16907, presented principles of selecting volumetric error models for three-axis machine tools. The principles of reducing these models due to the functional tasks of machine tools were also presented. The final result is a table of reduced models for three-axis machine tools. It determines the degree of the model and the experimental test program, which should be done to determine volumetric error.

Searching for potential relations between changes in 25(OH)D concentration and in physical fitness is an interesting scientific topic. Thus, the main purpose of this study was to investigate the changes in serum concentrations of 25(OH)D in young football players in conjunction with indicators determining bone resorption and physical fitness. A total of 35 young soccer players were tested during the autumn competition period. Biochemical analysis of blood, aerobic capacity, running speed and power tests (Wingate test, squat jump, counter movement jump) were carried out at the beginning and at the end of the competition period. Significant decrements in concentration of 25(OH)D from 33.9 ± 5.87 to 23.7 ± 5.58 ng/mL were noted after the analyzed competition period. There were no significant changes in aerobic capacity along the competition period. Significant improvements were observed in 10 m sprint, 30 m sprint (p &lt, 0.001), maximal power (p = 0.011) and total work capacity (p = 0.024). We found that the effect of changes in the players’ physical fitness does not occur in relation to 25 OH(D) concentration but occurs when these changes are analyzed as a function of the duration of the observation period. Changes in physical fitness of soccer players are determined by other factors then 25(OH)D concentration.

Many toxic effects of cocaine are attributed to reactive oxygen species (ROS) generated during its metabolism. Recently, it has been suggested that the biological action of ROS is often confused with endogenously generated reactive sulfur species (RSS). The aim of this study was to evaluate the impact of cocaine on thiols and RSS in the rat liver and kidney in the drug self-administration (SA) paradigm and the cocaine yoked delivery model (YC) followed by drug abstinence with extinction training. The level of thiols as well as RSS formed during anaerobic metabolism of cysteine and sulfate were assayed. In addition, the activity of enzymes involved in RSS formation and glutathione metabolism were determined. In the liver, following direct cocaine administration (SA and YC), the RSS levels decreased, while in the kidneys, cocaine increased the RSS contents in both groups. These changes were maintained in these tissues during drug abstinence. The level of sulfates was changed by cocaine only in the liver. In the kidney, cocaine shifted cysteine metabolism towards an anaerobic pathway. Our study demonstrates for the first time the changes in cysteine metabolism and thiol levels in the liver and kidney of rats after cocaine self-administration and abstinence.

Background This is the first study analyzing levels of physical activity in a sample of quarantined adults with chronic conditions. The aim of this study was to compare moderate- and vigorous-intensity physical activity levels in Spanish adults with chronic conditions before and during coronavirus disease 2019 (COVID-19) quarantine. Methods A cross-sectional online survey was administered during the COVID-19 quarantine in Spain. A total of 163 participants with chronic conditions (113 females and 47 males; age range 18–64 years) completed the survey. A total of 26 chronic conditions were included. Participants self-reported average minutes/day of moderate and vigorous physical activity before and during quarantine. Differences in moderate- and vigorous-intensity physical activity levels before and during COVID-19 quarantine (overall, by gender, by age, by number of chronic conditions and by each chronic condition) were assessed by Wilcoxon-signed rank test. Results During COVID-19 quarantine, there was a significant decrease of moderate-intensity physical activity in Spanish people with chronic conditions (in both males and females, in those aged 18–24, 25–34, 35–44 and 55–64 years, in those with multimorbidity, in those with one/two chronic condition/s, and in those diagnosed with asthma/hypercholesterolaemia/chronic skin disease/haemorrhoids). Also, there was a significant decrease of vigorous-intensity physical activity in Spanish males with chronic conditions and in those with multimorbidity. Conclusions These results should be considered to develop effective strategies of physical activity promotion targeting these specific groups when new quarantine or restriction measures are implemented, in order to avoid new significant decreases of physical activity in these vulnerable populations.

Neurochemical studies were previously performed on the effects of a 10 day extinction learning from cocaine self-administration on D2R and A2AR recognition and D2R Gi/o coupling in the ventral striatum. In the present study biochemical receptor binding and proximity ligation assay were used to study possible changes in the allosteric receptor-receptor interactions and the density of the A2AR-D2R heterocomplexes in the ventral striatum (nucleus accumbens shell) in extinction from cocaine self-administration including cue induced reinstatement of cocaine seeking. A significant and clear-cut reduction of active lever pressing was observed in extinction on day 10 from cocaine use. In cue induced reinstatement of cocaine self-administration a significant return in active lever presses developed. In extinction, significant increases in the density of A2AR-D2R and D2R-Sigma1R heterocomplexes were observed in nucleus accumbens shell. In contrast, cue-induced reinstatement of cocaine seeking produced no significant changes in these heteroreceptor complexes of the nucleus accumbens shell. In the 3H raclopride/quinpirole competition binding experiments, the extinction led to a significant increase in the D2R K

Background The objective was to compare levels of physical activity (PA) in a large sample of Spanish people with diabetes with and without cataracts. To our knowledge, this is the first study comparing PA levels in people with diabetes with and without cataracts in a large representative sample. Methods Cross-sectional data from the Spanish National Health Survey 2017 were analyzed (n = 1014 people with diabetes; 43.1% females; age range 15–69 years; mean age 58.4 ± 9.2 years). International Physical Activity Questionnaire (IPAQ) short form was used to measure PA. Total MET-min week−1 of PA were calculated and participants were divided into two categories according to American Diabetes Association PA guidelines: (i) Results The overall prevalence of cataract was 14.0% and the overall prevalence of people doing Conclusions Interventions to promote PA targeting people with both diabetes and cataracts are warranted.

Depression and cocaine use disorder represent frequent co-current diagnoses and the GABA

Purpose: The aim of the present study was to assess the association between levels of physical activity (PA) and the presence of cataracts in people aged 15–69years residing in Spain. Methods: Cross-sectional data from the Spanish National Health Survey 2017 were analysed (n=17,777≥15years; 52% females; self-weighting sample). The International Physical Activity Questionnaire (IPAQ) short form was used to measure PA. Total PA MET-minutes/week were calculated, and participants were divided into two categories: 1) Less than 600MET-minutes/week. 2) At least 600MET-minutes/week, equivalent to meeting current PA recommendations. Cataracts were self-reported in response to the question “Have you ever been diagnosed with cataracts?”. Multivariable logistic regression was used to assess associations overall and by age groups (15–49, 50–64, and 65–69years; 15–49 and 50–69years). Covariates included in the analysis were sex, education, BMI (Body Mass Index), multimorbidity, smoking, and alcohol consumption. Results: The overall prevalence of cataract was 3.7%, and the overall prevalence of participating in less than 600MET-minutes/week of PA was 30.2%. In the adjusted overall analysis, less than 600MET-minutes/week of PA was associated with significantly higher odds for cataract: OR=1.324 (95% CI=1.116–1.571). Age-stratified analyses showed that the association between PA and cataract was significant only in the age groups of 65–69years and 50–69years. Conclusions: A significant association between PA and cataract was observed in people aged 15–69years residing in Spain. Considering the impact on health and quality of life due to reduced PA in people with cataract, at least 600MET-minutes/week activity should be promoted. © 2020, © 2020 Taylor & Francis Group, LLC.

Manipulation of the serotonin (5-HT)1B receptors can modify the behavioral effects of amphetamine including its reinforcing properties. Focus of this study was to examine changes in 5-HT1B receptor protein expression in several brain structures linked to substance drug disorder in different stages of amphetamine addiction—single session of amphetamine self-administration, 20 consecutive days of amphetamine self-administration, and 3 and 14 days of extinction from chronic drug intake. “Yoked” procedure was employed to set apart pharmacological and motivational effects of amphetamine intoxication. Immunohistofluorescence was performed on brain slices containing the following regions: nucleus accumbens (NAc) shell and core, globus pallidum (GP) lateral and ventral, hippocampus (HIP), substantia nigra (SN), and ventral tegmental area (VTA). Single amphetamine session decreased the amount of 5-HT1B receptors in SN, VTA, and HIP in active and yoked rats. On the contrary, 20 days of chronic amphetamine exposure triggered elevation of 5-HT1B receptors exclusively in animals that voluntarily administered the drug in NAc core, GP ventral, and HIP. Furthermore, 14-day (but not 3-day) extinction from amphetamine increased the 5-HT1B receptor expression in ventral and lateral GP, HIP, and SN. This study is the first to demonstrate that exposure to amphetamine and its extinction alter the expression of 5-HT1B receptors in various rat brain regions, and those changes seem to be transient and region specific. Importantly, since increased expression of 5-HT1B receptor after chronic amphetamine self-administration was limited only to active group of animals, we suggest that 5-HT1B receptor is linked to motivational aspect of addiction.

Muscle strength and maximal speed are factors determining athlete’s results during competition. Their association with ACTN3 gene activity has been documented. The purpose of this study was the analysis of ACTN3 gene expression during a 2 month training cycle of soccer players and its correlation with the countermovement jump (CMJ) and squat jump (SJ). The study group consisted of 22 soccer players (aged 17‐18). The study material included peripheral blood lymphocytes. The relative expression (RQ) of the ACTN3 gene was analyzed by qPCR and performed before and after the two‐month training cycle. Before the training cycle low expression levels of ACTN3 (median RQ = 0.95) were observed, yet after the training cycle they were elevated (median RQ = 1.98) ( p = 0.003). There was an increase in performance of both jumps: SJ (p = 0.020) and CMJ (p = 0.012) at the end of the training cycle. A simultaneous increase in the ACTN3 gene expression level and height in both jump tests was observed in 73% of athletes (p > 0.05). There were no significant relationships between the ACTN3 gene expression level and the results of the CMJ and SJ. However, explosive strength is a complex feature shaped by many different factors and it could be the reason why we did not observe correlations between these variables.

Recent research indicates that selective NMDA receptor GluN2B subunit antagonists may become useful for the treatment of major depressive disorders. We aimed to examine in parallel the effect of the selective NMDA receptor GluN2B subunit antagonist CP-101,606 on the pituitary/serum hormone levels and on the regulation of cytochrome P450 in rat liver. CP-101,606 (20 mg/kg ip. for 5 days) decreased the activity of CYP1A, CYP2A, CYP2B, CYP2C11 and CYP3A, but not that of CYP2C6. The alterations in enzymatic activity were accompanied by changes in the CYP protein and mRNA levels. In parallel, a decrease in the pituitary growth hormone-releasing hormone, and in serum growth hormone and corticosterone (but not T3 and T4) concentration was observed. After a 3-week administration period of CP-101,606 less changes were found. A decrease in the CYP3A enzyme activity and protein level was still maintained, though no change in the mRNA level was found. A slight decrease in the serum concentration of corticosterone was also maintained, while GH level returned to the control value. The obtained results imply engagement of the glutamatergic system in the neuroendocrine regulation of cytochrome P450 and potential involvement of drugs acting on NMDA receptors in metabolic drug–drug interactions.

Drug craving and relapse risk during abstinence from cocaine are thought to be caused by persistent changes in transcription and chromatin regulation. Although several brain regions are involved in these processes, the hippocampus seems to play an important role in context-evoked craving and drug-seeking behavior. Only a few studies have examined epigenetic alterations during a period of cocaine abstinence. To investigate the effects of cocaine abstinence on DNA methylation and gene expression, rats that self-administered the drug underwent cocaine abstinence in two time points with extinction training. During the cocaine extinction, we observed elevated global 5-hydroxymethylcytosine(5-hmC) levels with a concurrent increase in Tet3 transcript levels. Moreover, we did not find significant alterations in the levels of Tet3 mRNA and 5-hmC in rats subjected to cocaine abstinence without extinction training (abstinence). Additionally, our findings demonstrated that the expression of Tet3 target genes was activated. Besides, altered DNA methylation was detected at promoter regions of miRNAs, such as miR-30d and miR-let7i. Further in silico analysis provided evidence that these two molecules targeted the 3'UTR region of theTet3gene and thus may contribute to its post-transcriptional regulation. This study has presented novel findings in the hippocampus of rats that underwent extinction training following cocaine self-administration. The alterations in the Tet3 gene expression and the level of 5-hmC may play an important role in extinction learning and the reduction of subsequent cocaine seeking. This article is protected by copyright. All rights reserved.

Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex. Microarray analysis showed significant upregulation of several genes encoding histone modification enzymes during early extinction training. Subsequent real-time PCR testing of these genes following cocaine self-administration or early (third day) and late (tenth day) extinction revealed elevated levels of their transcripts. Interestingly, we found the enrichment of Brd1 messenger RNA in rats self-administering cocaine that lasted until extinction training during cocaine withdrawal with concomitant increased acetylation of H3K9 and H4K8. However, despite elevated levels of methyl- and demethyltransferase-encoded transcripts, no changes in global di- and tri-methylation of histone H3 at lysine 4, 9, 27, and 79 were observed. Surprisingly, at the end of extinction training (10 days of cocaine withdrawal), most of the analyzed genes in the rats actively and passively administering cocaine returned to the control level. Together, the alterations identified in the rat prefrontal cortex may suggest enhanced chromatin remodeling and transcriptional activity induced by early cocaine abstinence; however, to know whether they are beneficial or not for the extinction of drug-seeking behavior, further in vivo evaluation is required. Electronic supplementary material The online version of this article (doi:10.1007/s12640-017-9728-7) contains supplementary material, which is available to authorized users.

Adenosine 2A receptor (A2AR) agonists were indicated to reduce cocaine reward and cocaine seeking mainly through activation of antagonistic allosteric A2AR-dopamine D2R (D2R) interactions in A2AR-D2R heteroreceptor complexes. Furthermore, it was shown that modulation of cocaine reward involves antagonistic A2AR-D2R interactions in the ventral but not the dorsal striatum in rats. In the current work the proximity ligation assay (PLA) was used to further study the A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell and core as well as the dorsal striatum under the influence of cocaine self-administration in rats. A significant increase in the A2AR-D2R PLA positive clusters was observed in the nucleus accumbens shell but not in the other regions vs yoked saline controls using the duolink software. Additionally, cocaine self-administration evoked a selective and significant increase in the density of D2R-sigma1R positive clusters in the nucleus accumbens shell vs yoked saline controls, while a significant reduction of the density of the D2R-sigma1R positive clusters was found in the dorsal part of the dorsal striatum. The results suggest that cocaine self-administration can reorganize A2AR and D2R into increased A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell associated with increases in the D2R-sigma1R heteroreceptor complexes in this region. This reorganization can contribute to the demonstrated anti-cocaine actions of A2A receptor agonists and the putative formation of A2AR-D2R-sigma1R heterocomplexes.

It is important to study differences in body composition, physical fitness and lifestyle behaviours between university students from different countries to develop country-specific recommendations on health promotion to provide to students when transitioning to university. The present study aimed to analyse differences in body composition, physical fitness and lifestyle behaviours between Polish and Spanish students of Sports Sciences. One-hundred-and-eighty-six male students participated (81 from Poland and 105 from Spain). Polish males were on average 21.5 &plusmn, 1.9 yrs old and Spanish males 21.5 &plusmn, 2.5. The body composition variables measured were body weight (kg), fat-free mass (FFM, kg and %), fat mass (FM, kg and %), total body water (TBW, kg and %), basal metabolic rate (BMR, kcal), body mass index (BMI, kg/m2), fat-free mass index (FFMI, kg/m2) and fat mass index (FMI, kg/m2). The physical fitness variables measured were squat jump (SJ, height in cm, power in watts and w/kg), countermovement jump (CMJ, height in cm, power in watts and w/kg), running speed (10, 20 and 30 m (time in s)), and progressive aerobic cardiovascular endurance run (PACER, stage, final speed in km/h, distance in m, VO2max in mL/kg/min). Lifestyle variables measured were vigorous physical activity (VPA, days/week, min/week), moderate physical activity (MPA, days/week, min/week), walking (days/week, min/week), sitting (min/week), meals/day, vegetables/day, fruits/day, seafood/week, dairy products/week, sweets, chips, fast food/week, litres of liquid/day, litres of sugary drinks/day, alcohol/week and cigarettes/day. In comparison to Spanish students, Polish students had greater FFM (kg), greater TBW (kg), higher BMR, greater power in SJ, greater height and power in CMJ, lower times in running speed tests (10 and 20 m) and greater consumption of vegetables and liquids. In comparison to Polish students, Spanish students participated in more physical activity, and consumed more seafood, more dairy products, less sugary drinks, less alcohol and less tobacco. VPA and consumption of vegetables and liquids had positive influences on body composition and physical fitness. According to these results, universities should promote a healthy lifestyle in order to improve body composition and physical fitness in male students studying sport science. In the cases of Spain and Poland, special attention should be paid to the weak points detected in this study. This would be useful for avoiding future risk of diseases such as obesity or diabetes.

Preclinical data indicate that ethanol produces behavioral effects that can be regulated by many neurotransmitters and neuromodulators like adenosine (A). The most important receptors with respect to the rewarding effects of ethanol seem to be the A

The aim of this study was to confirm that vitamin D supplementation of young soccer players during eight-week high-intensity training would have a significant effect on their motion activity. The subjects were divided into two groups: the experimental one, which was supplemented with vitamin D (SG, n = 20), and the placebo group (PG, n = 16), which was not supplemented with vitamin D. All the players were subjected to the same soccer training, described as High-Intensity Interval Training (HIIT). The data of the vitamin D status, time motion parameters and heart rate were collected just before and after the intervention. A significant increase in 25(OH)D concentration (119%) was observed in the supplemented group, while the non-supplemented group showed a decrease of 8.4%. Based on the obtained results, it was found that physical activity indicators in the players were significantly improved during small-sided games at the last stage of the experiment. However, taking into account the effect of supplementation with vitamin D, there were no statistically significant differences between the placebo and the supplemented groups, thus, the effect size of the conducted experiment was trivial.

Preclinical data indicate that ethanol produces behavioral effects that can be regulated by many neurotransmitters and neuromodulators like adenosine (A). The most important receptors with respect to the rewarding effects of ethanol seem to be the A2A receptors. This study used a transgenic strategy, specifically rats overexpressing the A2A receptor, to characterize the neurobiological mechanisms of ethanol consumption as measured by intermittent access to 20% ethanol in a two-bottle choice paradigm. In this model, no change in ethanol consumption was observed in transgenic animals compared to wild type controls during the acquisition/maintenance phase. Following alcohol deprivation, only transgenic rats overexpressing the A2A receptor exhibited escalation of ethanol consumption and drank more (by ca. 90%), but not significantly, ethanol than did the wild type rats. During ethanol withdrawal, the immobility time of rats overexpressing the A2A receptor in the forced swim test was lower than that of wild type rats. Moreover, transgenic rats withdrawn from ethanol, compared to the drug-naive transgenic animals, exhibited an increase above 70% in locomotion. The results indicated that the overexpression of A2A receptors may be a risk factor for the escalation of ethanol consumption despite the reduction in depression-like signs of ethanol withdrawal.

The purpose of this study was to investigate the influence of maximal oxygen uptake (VO2 max) on the glycemic changes during low and high intensity exercises in young type 1 diabetic patients. Twenty boys (age: 14.3 &plusmn, 1.6 years, height: 171.0 &plusmn, 11.3 cm, weight, 59.5 &plusmn, 12.8 kg) were divided into low-fit group (LFG, n = 10) and high-fit group (HFG, n = 10). According to the experimental design, participants performed three physical efforts (VO2 max test, mixed aerobic&ndash, anaerobic effort and aerobic effort) on the cycloergometer, during which real-time glycemia was measured. Mixed aerobic&ndash, anaerobic exercise demanded significantly smaller carbohydrate supplementation (0.2 &plusmn, 0.2 g/kg during exercise) than the aerobic test session (0.4 &plusmn, 0.3 g/kg during exercise). Moreover, patients with higher VO2 max had lower tendency for glycemic changes during the aerobic effort. The results of the current study suggest that young type 1 diabetic patients should perform different intensity activities using continuous glycemic monitoring system to avoid acute and chronic complications of the disease.

This paper deals with the formulation of a new method of measuring machine tool stiffness. The method enables measurements to be made in generalized coordinates, i.e. measurements of translational and torsional stiffness. It is based on geometrical transformations of a rigid body. It is universal, because it allows any positioning of displacement sensors on the surface of the tested object and to freely transform the excitation force. This allows testing the stiffness of various medium-sized machine tools - lathes, milling machines, etc. The validation of the measurement method (uncertainty budget) and validation of estimated measurement uncertainty are presented. The components of reproducibility and method-specific uncertainties have been shown to contribute significantly more to the budget than the components of metrological characteristics of the sensors used in the measurements. It was also shown which components of complex uncertainty can be omitted from the analysis without losing the accuracy of its estimation. The advantages of the proposed method have been demonstrated on the example of stiffness measurements on a milling machine.

Chronic exposure to drugs of abuse changes glutamatergic transmission in human addicts and animal models. N-acetylcysteine (NAC) is a cysteine prodrug that indirectly activates cysteine-glutamate antiporters. In the extrasynaptic space, NAC restores basal glutamate levels during drug abstinence and normalizes increased glutamatergic tone in rats during reinstatement to drugs of abuse. In initial clinical trials, repeated NAC administration seems to be promising for reduced craving in cocaine addicts.In this study, NAC-amide, called AD4 or NACA, was examined in intravenous cocaine self-administration and extinction/reinstatement procedures in rats. We investigated the behavioral effects of AD4 in the olfactory bulbectomized (OBX) rats, considered an animal model of depression. Finally, we tested rats injected with AD4 or NAC during 10-daily extinction training sessions to examine subsequent cocaine seeking.AD4 (25-75 mg kg(-1)) given acutely did not alter the rewarding effects of cocaine in OBX rats and sham-operated controls. However, at 6.25-50 mg kg(-1), AD4 decreased dose-dependently cocaine seeking and relapse triggered by cocaine priming or drug-associated conditioned cues in both phenotypes. Furthermore, repeated treatment with AD4 (25 mg kg(-1)) or NAC (100 mg kg(-1)) during daily extinction trials reduced reinstatement of drug-seeking behavior in sham-operated controls. In the OBX rats only, AD4 effectively blocked cocaine-seeking behavior.Our results demonstrate that AD4 is effective at blocking cocaine-seeking behavior, highlighting its potential clinical use toward cocaine use disorder.