Microglial TNFα controls daily changes in synaptic GABAARs and sleep slow waves.

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNFα. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNFα and P2RX7. We further show that microglia-specific depletion of TNFα alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves, and support memory consolidation.

Enhancing Phytoextraction Potential of Brassica napus for Contaminated Dredged Sediment Using Nitrogen Fertilizers and Organic Acids.

Dredged sediment contaminated with heavy metals can be remediated through phytoremediation. The main challenge in phytoremediation is the limited availability of heavy metals for plant uptake, particularly in multi-contaminated soil or sediment. This study aimed to assess the effect of the nitrogen fertilizers (ammonium nitrate (AN), ammonium sulfate (AS), and urea (UR)), organic acids (oxalic (OA) and malic (MA) acids), and their combined addition to sediment on enhancing the bioavailability and phytoremediation efficiency of heavy metals. The sediment dredged from Begej Canal (Serbia) had high levels of Cr, Cd, Cu, and Pb and was used in pot experiments to cultivate energy crop rapeseed (Brassica napus), which is known for its tolerance to heavy metals. The highest accumulation and translocation of Cu, Cd, and Pb were observed in the treatment with AN at a dose of 150 mg N/kg (AN150), in which shoot biomass was also the highest. The application of OA and MA increased heavy metal uptake but resulted in the lowest biomass production. A combination of MA with N fertilizers showed high uptake and accumulation of Cr and Cu.

Depriving Mice of Sleep also Deprives of Food.

Both sleep-wake behavior and circadian rhythms are tightly coupled to energy metabolism and food intake. Altered feeding times in mice are known to entrain clock gene rhythms in the brain and liver, and sleep-deprived humans tend to eat more and gain weight. Previous observations in mice showing that sleep deprivation (SD) changes clock gene expression might thus relate to altered food intake, and not to the loss of sleep per se. Whether SD affects food intake in the mouse and how this might affect clock gene expression is, however, unknown. We therefore quantified (i) the cortical expression of the clock genes Per1, Per2, Dbp, and Cry1 in mice that had access to food or not during a 6 h SD, and (ii) food intake during baseline, SD, and recovery sleep. We found that food deprivation did not modify the SD-incurred clock gene changes in the cortex. Moreover, we discovered that although food intake during SD did not differ from the baseline, mice lost weight and increased food intake during subsequent recovery. We conclude that SD is associated with food deprivation and that the resulting energy deficit might contribute to the effects of SD that are commonly interpreted as a response to sleep loss.

Lipids and Antiplatelet Therapy: Important Considerations and Future Perspectives.

Lipids play an essential role in platelet functions. It is known that polyunsaturated fatty acids play a role in increasing platelet reactivity and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases' incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies discontinuation of clopidogrel in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed "on-demand" in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.

Differences in anthropometrics characteristics and body composition between two elite youth male basketball national teams - participants at u18 European Championship 2019 / Diferencias en las características antropométricas y la composición corporal entre dos equipos nacionales de baloncesto masculino juvenil de élite - participantes en el Campeonato de Europa u18 2019

SUMMARY: The aim of this research was to determine the differences among the male basketball players of the National team of Montenegro U18 and the National team of Republic of North Macedonia, in terms of their anthropometric characteristics and body composition. A sample of 27 subjects was divided into two sub-samples. The first sub-sample of the subjects consisted of 15 players of the National team of Montenegro, average age 17.6±0.63, while the other sub-sample consisted of 12 players of the National team of Republic of North Macedonia, average age of 17.17± 0.72. All players were tested in Podgorica, in lasting period of two days, while they held preparations for the European Championship. Anthropometric characteristics and body composition were evaluated by a battery of eleven variables: body height (cm), body weight (kg), triceps skinfold, back skinfold, biceps skinfold, abdominal skinfold, thigh skinfold, calf skinfold, body mass index (BMI), percentage of fat and muscle mass (kg). Differences in anthropometric characteristic and composition of the body of the basketball players of two national teams were determined by using a discriminatory parametric procedure with t-test for small independent samples (p<0.05). The players of the two teams were found to differ statistically in thigh skinfold. Furthermore, it is concluded that Montenegro players are taller and heavier and have higher muscle mass than North Macedonian players, with approximate skinfolds, BMI and fat percentage values.

RESUMEN: El objetivo de esta investigación fue determinar las diferencias en las características antropométricas y composición corporal entre los jugadores de baloncesto masculino del equipo nacional de Montenegro U18 y el equipo nacional de la República de Macedonia del Norte. Una muestra de 27 sujetos se dividió en dos submuestras. La primera sub muestra consistió en 15 jugadores del equipo nacional de Montenegro, con una edad promedio de 17,6 ± 0,63 años. La otra muestra consistió en 12 jugadores del equipo nacional de la República de Macedonia del Norte, con un promedio edad de 17,17 ± 0,72 años. Todos los jugadores fueron evaluados en Podgorica, durante un período de dos días, mientras realizaban los preparativos para el Campeonato de Europa. Las características antropométricas y la composición corporal se evaluaron mediante una batería de once variables: altura (cm), peso (kg), pliegue de tríceps, pliegue de espalda, pliegue de bíceps, pliegue abdominal, pliegue de muslos, pliegue de pantorrilla, índice de masa corporal (IMC), porcentaje de grasa y masa muscular (kg). Se determinaron las diferencias en las características antropométricas y la composición del cuerpo de los jugadores de baloncesto de dos equipos nacionales a través de un procedimiento paramétrico discriminatorio con prueba t para muestras independientes (p <0,05). Se determinó que los jugadores de ambos equipos difieren estadísticamente en el pliegue del muslo. Además, se concluyó que en comparación con los jugadores de Macedonia del Norte los jugadores de Montenegro son de mayor altura y peso, además de contar con una mayor masa muscular, con valores aproximados de pliegues cutáneos, IMC y porcentaje de grasa.

Modelling and optimisation of treatment parameters in high-dose-rate mono brachytherapy for localised prostate carcinoma using a multilayer artificial neural network and a genetic algorithm: Pilot study.

BACKGROUND: High-dose-rate mono brachytherapy (HDR-MB) is employed in the treatment of prostate carcinoma (CaP). As an ideal plan of CaP brachytherapy cannot be created, it is necessary to identify a reliable tool to optimise the parameters of HDR-MB. This paper applies a multilayer artificial neural network (MANN) and a genetic algorithm (GA) to optimise brachytherapy parameters based on an individual dose-volumetric analysis. METHODS: Patients with localised CaP of various risks were treated with HDR-MB. Consecutive levels of the biochemical control parameter (prostate specific antigen (PSA) nadir) have been collected after completion of HDR-MB in the range 2-9 years. The Kaplan-Meier regression analysis of biochemical-free survival (BFS) was applied. The clinical risk of recurrent CaP (RCaP), the therapy dose (TD), TD coverage index (CI100%) and PSA nadir were modelled using the MANN and GA. RESULTS: In the low-risk group, BFS was achieved in 100% of treated patients, while in the group of patients with high risk, BFS was achieved in 95.8% of treated patients. The MANN-GA model optimises a TD of 47.3 Gy and CI100% of 1.14 as well as a TD of 50.4 Gy and CI100% of 1.6 for the low-risk group and high-risk group, respectively, of localised CaP. The optimised PSA nadir was 0.047 and 0.25 ng cm-3 for low-risk group and high-risk group, respectively. CONCLUSIONS: The developed MANN-GA model presents a method for optimising the treatment parameters in radiation therapy, which could be a valuable tool in planning of the HDR-MB.

Physical Activity as a Function of Women's Health.

Physical activity means any form of body movement that is associated with certain metabolic demands. At the same time, physical activity is one of the most important steps in the maintenance, protection and improvement of health. There is strong evidence to suggest that higher levels of physical activity are associated with numerous preventive effects and therapeutic effects in the treatment of many diseases. Although they account for a larger portion of the population, physical inactivity is more often registered in women, which can be attributed to a variety of reasons--ranging from anatomical and physiological to the socio-psychological. The present paper discusses some of the most important benefits associated with physical activity in women, to encourage their greater participation in various forms of physical activity.

Oxidized Low Density Lipoprotein and High Sensitive C-Reactive Protein in Non-Diabetic, Pre-Diabetic and Diabetic Patients in the Acute Phase of the First Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

BACKGROUND: Oxidized low density lipoprotein (ox-LDL) and high-sensitive C-reactive protein (hs-CRP) are elevated in diabetes mellitus (DM) and associated with accelerated atherosclerosis. Little is known about their dynamics in the acute phase of ST segment elevation myocardial infarction (STEMI), especially in relation to the presence of DM and pre-diabetes (pre-DM). This study aimed to analyze time-dependent changes in ox-LDL and hs-CRP regarding the presence of pre-DM and DM in STEMI patients treated by primary percutaneous coronary intervention (pPCI). METHODS: In 103 consecutive patients with the first anterior STEMI ox-LDL and hs-CRP were measured before pPCI, on day 2 and day 7 after pPCI. RESULTS: Patients were classified into: non-diabetics, pre-diabetics and diabetics. In each group the maximal ox-LDL concentration was found on admission, decreased on day 2 and reached the lowest values on day 7 (p<0.001). Diabetics had the highest ox-LDL concentrations compared to pre-diabetics and non-diabetics (on admission: p=0.028, on day 2: p=0.056, on day 7: p=0.004). hs-CRP concentration rose from admission, reached its peak on day 2 and decreased on day 7, in each group (p<0.001). Significant differences in hs-CRP concentrations were found between non-diabetics and pre-diabetics on admission (p=0.018) and day 2 (p=0.026). In a multivariate analysis DM was an independent determinant of high ox-LDL concentrations. Both ox-LDL and hs-CRP significantly correlated with Killip class, left ventricular ejection fraction, NT-proBNP and peak troponin I. CONCLUSIONS: In patients with the first STEMI treated by pPCI there were significant differences in ox-LDL and hs-CRP concentrations between non-diabetics, pre-diabetics and diabetics. Ox-LDL and hs-CRP concentrations were related to heart failure parameters.

[The importance of tests applied to evaluate the effectiveness of antiplatelet therapy in patients with recurrent coronary stent thrombosis].

BACKGROUND: Stent thrombosis is potentially lethal complication with huge economic burden. The role of insufficient response to antiplatelet therapy is still unclear reason for its occurrence. CASE REPORT: We presented 54-year-old man with recurrent stent thrombosis on the 4th, 9th and 12th day after the primary percutaneous coronary intervention in spite of double antiaggregation therapy (aspirin+clopidogrel). All possible procedural causes were excluded and reimplantation of intracoronary stent was insufficient to resolve the problem, so four platelet tests were performed: flow cytometry, Platelet Function Analyzer-100 test, aggregometry, and determination of gene polymorphism for P2Y12 receptor (directly involved in the mechanism of thienopyridine), and GPIIbIIIa receptor (final receptor in aggregation). The patient was the carrier of the major haplotype H1H1 for P2Y12 receptor and minor A1A2 for GPIIbIIIa receptor. The results of all the performed tests showed insufficient antiplatelet effect of aspirin and sufficient response to thienopyridin (not to clopidogrel, but to ticlopidine). CONCLUSION: Performance of platelet function tests is necessary in the case of major adverse cardiac events especially stent thrombosis, after implantation of intracoronary stent.

Evaluation of myocardial relaxation in conditions of cardiac remodeling.

The term cardiodynamics refers to dynamic events associated with cardiac contraction and relaxation. The occurring wave of excitement spreads very quickly along the entire atrial musculature and after a brief AV retention it affects all muscle cells of the ventricles. Excitation, that is, the increase in action potentials, precedes the contraction of the myocardium, which follows the "all or none" rule. Each contraction results in relaxation of the myocardium, so that the contraction and relaxation cycles continually follow each other in succession. The entire cardiodynamics, hemnodinamics, i.e., signaling mechanisms of the heart are altered in the remodeling (alternation) condition of the left ventricular myocardium, i.e., the musculature and the whole arterial wall. Remodeling of the cardiac wall and layers of the arterial wall is a negative factor, because it leads to disturbances of the cardiac contraction and relaxation cycles and incites progression of the arterial hypertension, emergence of atherosclerosis and arterial stenosis. Today, the genetic base of the cardiac remodeling is the object of intensive studies. Cardiomyopathies are primary disorders of the myocardium associated with abnormalities of the cardiac wall thickness, the size of chambers, contractions, relaxations, signal conduct and rhythm. They are the major cause of morbidity and mortality for all age groups. Mechanisms of these events on the molecular level will be discussed in the following study.