Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition

The type 1 adenylyl cyclase (AC1) is an activity-dependent, calcium-stimulated adenylyl cyclase expressed in the nervous system that is implicated in memory formation. We examined the locomotor activity, and impulsive and social behaviors of AC1+ mice, a transgenic mouse strain overexpressing AC1 in the forebrain. Here we report that AC1+ mice exhibit hyperactive behaviors and demonstrate increased impulsivity and reduced sociability. In contrast, AC1 and AC8 double knock-out mice are hypoactive, and exhibit increased sociability and reduced impulsivity. Interestingly, the hyperactivity of AC1+ mice can be corrected by valproate, a mood-stabilizing drug. These data indicate that increased expression of AC1 in the forebrain leads to deficits in behavioral inhibition

Aging and Future Healthcare Expenditure: A Consistent Approach

The impact of aging on healthcare expenditure (HCE) has been at the center of a prolonged debate. This paper purports to shed light on several issues of this debate by presenting new evidence on the "red herring" hypothesis advanced by Zweifel, Felder and Meier (1999). This hypothesis amounts to distinguishing a mortality from a morbidity component in healthcare expenditure (HCE) and claiming that failure to make this distinction results in excessive estimates of future growth of HCE. A re-estimation based on a much larger data set is performed, using the refined econometric methodology. The main contribution is consistency, however. Rather than treating the mortality component as a residual in forecasting, its dynamics are analyzed in the same detail as that of the morbidity component when predicting the impact of population aging on the future growth of HCE. For the case of Switzerland, it finds this impact to be relatively small regardless of whether or not the mortality component is accounted for, thus qualifying the "red herring" hypothesi

The [4+2]‐Cycloaddition of α‐Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero‐Diels–Alder Reactions—Experimental and Computational Studies

The [4+2]‐cycloadditions of α‐nitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styryl‐substituted 4H‐1,5,2‐oxathiazines in moderate to good yields. Of the eight conceivable hetero‐Diels–Alder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the α‐nitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bis‐heterocyclic [4+2]‐cycloadducts. The experiments are supported by high‐level DFT calculations that were also extended to related hetero‐Diels–Alder reactions of other nitroso compounds and thioketones. These calculations reveal that the title cycloadditions are kinetically controlled processes confirming the role of thioketones as superdienophiles. The computational study was also applied to the experimentally studied thiochalcone dimerization, and showed that the 1,2‐dithiin and 2H‐thiopyran isomers are in equilibrium with the monomer. Again, the DFT calculations indicate kinetic control of this process

Self-made pest control products for organic cotton production in Nimar region, Madhya Pradesh, India

Homemade organic pest control products offer an ecological, healthy and low-cost alternative to ready-made products. Yet the recipes are not standardised and the products vary in quality and concentration of the active ingredients. bioRe R, together with the Research Institute of Organic Agriculture (FiBL), engages in research activities to address this challenge and improve pest management strategies in organic farming. During the cotton cropping season 2013–14 one on-station and two on-farm trials were conducted with the objective of comparing different spraying intervals of the most commonly used home-made organic pest control products in order to identify an optimum level of crop protection. The study focused on the effect of the spraying intervals on the most important sucking pests. Besides sucking pest incidences, data on plant stress symptoms and yield formation as well as economic parameters were also collected. Additional on-station trials were established to investigate different measures of early stage crop protection and to detect specific effects of three self made products against certain sucking pests. The products were prepared according to recipes standardised by bioRe R after careful research and hands on experience of its associated scientists and extension workers. This knowledge was reproduced in pictorial technical leaflets, which are easy-to-understand for the local farmers. A total of 11 leaflets — on seed treatments, early stage protection measures, pest control sprays, effective spraying technique and growth promoter were designed in both English and Hindi and will be used for dissemination activities. On-station results were inconclusive due to low pest pressure in this season, as well as the small size of the trial plots. Results of on-farm trials revealed that a suitable strategy for pest monitoring is needed for farmers to determine at what time point pest control interventions are indicated. Further research is needed to understand the specific effects of homemade products on the different insect species. Optimised dosage and application techniques have to be worked out along with other options for integrated pest control (e.g. bird perches, border crops, soil enhancement practices) that could reduce the frequency of time-consuming spraying. These activities would best be conducted in on-farm trials

Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas

Background: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas. Patients and methods: Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy. Results: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia ≥grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred. Conclusions: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patient

Artificial intelligence applications and cataract management: A systematic review

Artificial intelligence (AI)-based applications exhibit the potential to improve the quality and efficiency of patient care in different fields, including cataract management. A systematic review of the different applications of AI-based software on all aspects of a cataract patient's management, from diagnosis to follow-up, was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All selected articles were analyzed to assess the level of evidence according to the Oxford Centre for Evidence-Based Medicine 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation system. Of the articles analyzed, 49 met the inclusion criteria. No data synthesis was possible for the heterogeneity of available data and the design of the available studies. The AI-driven diagnosis seemed to be comparable and, in selected cases, to even exceed the accuracy of experienced clinicians in classifying disease, supporting the operating room scheduling, and intraoperative and postoperative management of complications. Considering the heterogeneity of data analyzed, however, further randomized controlled trials to assess the efficacy and safety of AI application in the management of cataract should be highly warranted

A Neurotrophin Signaling Cascade Coordinates Sympathetic Neuron Development through Differential Control of TrkA Trafficking and Retrograde Signaling

AbstractA fundamental question in developmental biology is how a limited number of growth factors and their cognate receptors coordinate the formation of tissues and organs endowed with enormous morphological complexity. We report that the related neurotrophins NGF and NT-3, acting through a common receptor, TrkA, are required for sequential stages of sympathetic axon growth and, thus, innervation of target fields. Yet, while NGF supports TrkA internalization and retrograde signaling from distal axons to cell bodies to promote neuronal survival, NT-3 cannot. Interestingly, final target-derived NGF promotes expression of the p75 neurotrophin receptor, in turn causing a reduction in the sensitivity of axons to intermediate target-derived NT-3. We propose that a hierarchical neurotrophin signaling cascade coordinates sequential stages of sympathetic axon growth, innervation of targets, and survival in a manner dependent on the differential control of TrkA internalization, trafficking, and retrograde axonal signaling

The Banathy Conversation Methodology

Context: Thirty years ago, members of the systems science community discovered that at their conferences, more was being accomplished in the breaks than in the sessions. Led by Bela H. Banathy, they cancelled the sessions and created a conversation methodology that has proven far more effective. Dozens of conversations have now been held around the world. Problem: At a recent conversation in Linz, Austria, a team devoted its inquiry to the Banathy Conversation Methodology (BCM) itself, asking, in particular, how to develop and spread the methodology further, beyond the systems science community. Method: The team captured key features and benefits of BCM and developed new tools. Results: Described herein are the development of the methodology, its theoretical underpinnings, the methodology itself, heuristics for successful conversations, and an example of how the methodology is spreading. Implications: Ultimately, the hope is to develop the methodology in such ways that communities could apply it to meet significant challenges and co-create their futures