Adenosine receptor expression and function in rat striatal cholinergic interneurons

1. Cholinergic neurons were identified in rat striatal slices by their size, membrane properties, sensitivity to the NK(1) receptor agonist (Sar(9), Met(O(2))(11)) Substance P, and expression of choline acetyltransferase mRNA. A(1) receptor mRNA was detected in 60% of the neurons analysed, and A(2A) receptor mRNA in 67% (n=15). 2. The A(1) receptor agonist R-N(6)-(2-phenylisopropyl)adenosine (R-PIA) hyperpolarized cholinergic neurons in a concentration dependent manner sensitive to the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM). 3. In dual stimulus experiments, the A(2A) receptor antagonist 8-(3-chlorostyryl)caffeine (CSC, 500 nM) decreased release of [(3)H]-acetylcholine from striatal slices (S2/S1 0.78±0.07 versus 0.95±0.05 in control), as did adenosine deaminase (S2/S1 ratio 0.69±0.05), whereas the A(1) receptor antagonist DPCPX (100 nM) had no effect (S2/S1 1.05±0.14). 4. In the presence of adenosine deaminase the adenosine A(2A) receptor agonist 2-p-((carboxyethyl)phenylethylamino)-5′-N-ethylcarboxamidoadenosine (CGS21680, 10 nM) increased release (S2/S1 ratio 1.03±0.05 versus 0.88±0.05 in control), an effect blocked by the antagonist CSC (500 nM, S2/S1 0.68±0.05, versus 0.73±0.08 with CSC alone). The combined superfusion of bicuculline (10 μM), saclofen (1 μM) and naloxone (10 μM) had no effect on the stimulation by CGS21680 (S2/S1 ratio 0.99±0.04). 5. The A(1) receptor agonist R-PIA (100 nM) inhibited the release of [(3)H]-acetylcholine (S2/S1 ratio 0.70±0.03), an effect blocked by DPCPX (S2/S1 ratio 1.06±0.07). 6. It is concluded that both A(1) and A(2A) receptors are expressed on striatal cholinergic neurons where they are functionally active

An exploratory analysis of the current status and potential of service-oriented and data-driven business models within the sheet metal working sector : insights from interview-based research in small and medium-sized enterprises

Responding to changing value creation processes in the sheet metal working sector, where the complexity and interchangeability of products challenge traditional differentiation strategies, this exploratory analysis examines the integration of service-oriented and data-driven business models as new paths to ensure competitiveness, especially for small and medium-sized enterprises (SMEs). This study aims to capture the current state and challenges associated with the implementation of these business models in this sector. This research was conducted through semi-structured interviews with SMEs in the industry. The findings indicate that service-oriented and data-driven business models are not yet widely adopted and that manufacturing companies require support in their implementation. Fields of action were identified for the industry. These are “Creating awareness and understanding”, “Recognizing added value”, “Increasing company maturity”, and “Understanding the change process”. Cooperation between science and industry is essential in tackling these fields of action to ensure the successful integration of such business models in manufacturing companies. This paper identifies challenges in the fields of action that companies must address through a structured approach, promoting awareness, recognizing value, improving organizational maturity, and understanding the change process to successfully implement service-oriented and data-driven business models.State Ministry of Baden-Wuerttemberg for Economic Affairs, Labor and Tourism and implemented by VDI/VD

Pulsed-field ablation-based pulmonary vein isolation:acute safety, efficacy and short-term follow-up in a multi-center real world scenario

Purpose: Pulsed-field ablation (PFA) is a new energy source to achieve pulmonary vein isolation (PVI) by targeted electroporation of cardiomyocytes. Experimental and controlled clinical trial data suggest good efficacy of PFA-based PVI. We aimed to assess efficacy, safety and follow-up of PFA-based PVI in an early adopter routine care setting. Methods: Consecutive patients with symptomatic paroxysmal or persistent atrial fibrillation (AF) underwent PVI using the Farawave® PFA ablation catheter in conjunction with three-dimensional mapping at two German high-volume ablation centers. PVI was achieved by applying 8 PFA applications in each PV. Results: A total of 138 patients undergoing a first PVI (67 ± 12 years, 66% male, 62% persistent AF) were treated. PVI was achieved in all patients by deploying 4563 applications in 546 PVs (8.4 ± 1.0/PV). Disappearance of PV signals after the first application was demonstrated in 544/546 PVs (99.6%). More than eight PFA applications were performed in 29/546 PVs (6%) following adapted catheter positioning or due to reconnection as assessed during remapping. Mean procedure time was 78 ± 22 min including pre- and post PVI high-density voltage mapping. PFA catheter LA dwell-time was 23 ± 9 min. Total fluoroscopy time and dose area product were 16 ± 7 min and 505 [275;747] cGy*cm2. One pericardial tamponade (0.7%), one transient ST-elevation (0.7%) and three groin complications (2.2%) occurred. 1-year follow-up showed freedom of arrhythmia in 90% in patients with paroxysmal AF (n = 47) and 60% in patients with persistent AF (n = 82, p = 0.015). Conclusions: PFA-based PVI is acutely highly effective and associated with a beneficial safety and low recurrence rate. Graphical abstract

The first Forecasters Handbook for West Africa

Bridging the gap between rapidly moving scientific research and specific forecasting tools, Meteorology of Tropical West Africa: The Forecasters' Handbook’, gives unprecedented access to the latest science and combines this with pragmatic approaches to forecasting. It is set to change the way forecasters, researchers and students learn about tropical meteorology and will serve to drive demand for new forecasting tools. The Handbook builds upon the legacy of the AMMA project, making the latest science applicable to forecasting in the region. By bringing together, at the outset, researchers and forecasters from across the region, and linking to applications, user communities and decision-makers, the Forecasters’ Handbook provides a template for finding much needed solutions to critical issues such as building resilience to climate change in West Africa

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.; We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.; Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress