Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens

Cocaine-induced plasticity in the glutamatergic transmission and its N-methyl-d-aspartate (NMDA) receptors are critically involved in the development of substance use disorder. The presynaptic active zone proteins control structural synaptic plasticity; however, we are still far from understanding the molecular determinants important for cocaine seeking behavior. The aim of this study was to investigate the effect of cocaine self-administration and different conditions of cocaine forced abstinence on the composition of the NMDA receptor subunits and on the levels of active zone proteins, i.e., Ras-related protein 3A (Rab3A), Rab3 interacting molecules 1 (RIM1) and mammalian uncoordinated protein 13 (Munc13) in the rat nucleus accumbens. We found an up-regulation of the accumbal levels of GluN1 and GluN2A following cocaine self-administration that was paralleled by an increase of Munc13 and RIM1 levels. At the same time, we also demonstrated that different conditions of cocaine abstinence abolished changes in NMDA receptor subunits (except for higher GluN1 levels after cocaine abstinence with extinction training), while an increase in the Munc13 concentration was shown in rats housed in an enriched environment. In conclusion, cocaine self-administration is associated with the specific up-regulation of the NMDA receptor subunit composition and is related with new presynaptic targets controlling neurotransmitter release. Moreover, changes observed in cocaine abstinence with extinction training and in an enriched environment in the levels of NMDA receptor subunit and in the active zone protein, respectively, may represent a potential regulatory step in cocaine-seeking behavior

Analisis Pengaruh Perlakuan Alkali Terhadap Wettability Serat Tunggal Widuri

Along with its development, composites do not only use synthetic fibers, but there are already composite reinforcing materials made from natural fibers. The advantages of natural fiber as a reinforcing material for composite materials are: the ratio between strength and density is quite high, corrosion resistance, low cost and easy manufacturing process. The use of natural fibers as reinforcement for polymer materials provides opportunities for some natural fibers to be used as reinforcement for polymer composites, one of which is thistle fiber. The treatment used was alkaline treatment (NaOH) with percentages of 2%, 3%, 4%, 5%, 6%, and 7%, respectively, and the soaking time of 30, 60, 90, 120 minutes, and fiber. Widuri bark without treatment as a comparison. The purpose of this study was to determine the effect of the concentration of alkaline solution and the duration of immersion on the wettability of single widuri fibers. Single fiber testing refers to ASTM D3379 standard. From the results of the fiber contact angle test with 6% NaOH treatment for 120 minutes with a cos price of 0.906725322 with a droplet geometry that tends to be barrel. Meanwhile, fiber treated with 3% NaOH for 60 minutes had the lowest cos value of 0.472037963 with a droplet geometry that tends to be clam-shel

Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/mass spectrometry (HPLC-MS2) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity

Factors associated with material deprivation in persons with multiple sclerosis in Switzerland: Cross-sectional data from the Swiss Multiple Sclerosis Registry.

BACKGROUND Multiple sclerosis (MS) impacts education, future career pathways and working capability and therefore may negatively impact the financial situation of persons with MS (pwMS) in Switzerland. We therefore investigated the financial situation and its influencing sociodemographic and disease-specific factors of pwMS compared to the general Swiss population with focus on material deprivation (MD). METHODS Data on the financial situation of pwMS were collected via a specific questionnaire added to the regular, semi-annual follow-up assessments of the Swiss Multiple Sclerosis Registry. Questions were taken in an unmodified format from the standardized "Statistics on Income and Living Conditions" (SILC) questionnaire 2019 of the Federal Statistical Office of Switzerland which evaluates the financial situation of the general Swiss population, enabling a direct comparison of pwMS with the general Swiss population. RESULTS PwMS were 1.5 times more frequently affected by MD than the general Swiss population (6.3% of pwMS versus 4.2% of the general Swiss population) which was confirmed in a multivariable logistic regression analysis of pooled SILC and Swiss Multiple Sclerosis Registry (SMSR) data. High symptom burden, having only mandatory schooling, well as having a pending disability insurance application (as opposed to no application or receiving benefits) were associated with a higher odds of MD whereas higher education, older age, having a Swiss citizenship, living with a spouse or a partner or being currently employed were independently associated with a lower odds of MD. CONCLUSION MS has a negative impact on the financial situation and is associated with MD. PwMS with a high symptom burden at the transition from work force to receiving disability benefits appeared to be vulnerable for MD. Higher education, older age, having a Swiss citizenship, living with a spouse or a partner or being currently employed were independently associated with a lower odds of MD

Distribution of preoperative angle alpha and angle kappa values in patients undergoing multifocal refractive lens surgery based on a positive contact lens test

Purpose: To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). Methods: Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. Results: Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (<0.5mm). In the 1-year follow-up, UCVA improved by 0.68 logMAR (SD 0.51; p<0.001) from baseline. Eyes with both small angle alpha and kappa sizes improved by 0.78 logMAR (SD 0.56), as did eyes with high (≥0.5mm) angle sizes (0.82 logMAR (SD 0.53). UCVA of eyes (n=24) with high alpha but low kappa sizes improved less (-0.31 logMAR (SD 0.13; p=0.019)). Conclusion: Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes. Keywords: Angle alpha; Angle kappa; Decision-making; Multifocal intraocular lens; Refractive lens surgery

Biological properties of surface layers for ring of heart valve application

Oryginalna sztuczna komora wspomagania serca POLVAD opracowana w Polsce, została zastosowana dotychczas w leczeniu ponad 210 pacjentów. Najdłuższe wspomaganie serca za pomocą komory POLVAD trwało ponad rok. Dla protezy tej opracowywana jest innowacyjna zastawka dyskowa, z nisko profilowym pierścieniem wykonanym ze stopu tytanu. Dla zminimalizowania trombogenności pierścienia zastawki opracowano dyfuzyjne warstwy powierzchniowe: azotowaną typu TiN+Ti2N+αTi(N) i tlenoazotowaną typu TiO2+TiN+Ti2N+αTi(N), wytwarzane obróbką jarzeniową na potencjale plazmy. Trombogenność różnych kompozycji warstw została porównana w aspekcie aktywacji i adhezji płytek krwi do powierzchni biomateriału. Oceniono również wpływ metody sterylizacji biomateriału na intensywność adhezji trombocytów do jego powierzchni. Warstwy TiN oraz TiO2wykazały najniższą trombogenność, przy czym dla warstwy TiN korzystniejsza jest sterylizacja gazowa, podczas gdy dla warstwy TiO2- sterylizacja plazmowa.The original ventricular assist device POLVAD developed in Poland was used in over 210 patients so far. The longest POLVAD heart assistance excided one year. The innovative tilting disk valve with low profile ring made of titanium is developed for POLVAD. To minimize the valve ring thrombogenicity the diffusive surface layers were manufactured: nitriding TiN+Ti2N+αTi(N) and oxynitriding TiO2+TiN+Ti2N+αTi(N), in the glow discharge process on the plasma potential level. The thrombogenicity of different layers compositionwas compared regarding platelets activation and platelets adhesion to the material surface. The influence of material sterilization method on the platelets adhesion intensity was evaluated in addition. The nitriding TiN and oxynitriding TiO2layers have demonstrated the lowest thrombogenicity while the gas sterilization was the most profitable for nitriding layers – TiN and the plasma sterilization for oxynitriding layers – TiO2

Effects of non‐steroidal anti‐inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses. EAACI task force on eicosanoids consensus report in times of COVID‐19

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti‐inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS‐CoV‐2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID‐19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs‐exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID‐19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID‐19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research

The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts

BACKGROUND: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. METHODS: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. RESULTS: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). CONCLUSIONS: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition