Enhanced prefrontal serotonin 5-HT1A currents in a mouse model of Williams-Beuren syndrome with low innate anxiety

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the hemizygous deletion of 28 genes on chromosome 7, including the general transcription factor GTF2IRD1. Mice either hemizygously (Gtf2ird1+/−) or homozygously (Gtf2ird1−/−) deleted for this transcription factor exhibit low innate anxiety, low aggression and increased social interaction, a phenotype that shares similarities to the high sociability and disinhibition seen in individuals with WBS. Here, we investigated the inhibitory effects of serotonin (5-HT) on the major output neurons of the prefrontal cortex in Gtf2ird1−/− mice and their wildtype (WT) siblings. Prefrontal 5-HT receptors are known to modulate anxiety-like behaviors, and the Gtf2ird1−/− mice have altered 5-HT metabolism in prefrontal cortex. Using whole cell recording from layer V neurons in acute brain slices of prefrontal cortex, we found that 5-HT elicited significantly larger inhibitory, outward currents in Gtf2ird1−/− mice than in WT controls. In both genotypes, these currents were resistant to action potential blockade with TTX and were suppressed by the selective 5-HT1A receptor antagonist WAY-100635, suggesting that they are mediated directly by 5-HT1A receptors on the recorded neurons. Control experiments suggest a degree of layer and receptor specificity in this enhancement since 5-HT1A receptor-mediated responses in layer II/III pyramidal neurons were unchanged as were responses mediated by two other inhibitory receptors in layer V pyramidal neurons. Furthermore, we demonstrate GTF2IRD1 protein expression by neurons in layer V of the prefrontal cortex. Our finding that 5-HT1A-mediated responses are selectively enhanced in layer V pyramidal neurons of Gtf2ird1−/− mice gives insight into the cellular mechanisms that underlie reduced innate anxiety and increased sociability in these mice, and may be relevant to the low social anxiety and disinhibition in patients with WBS and their sensitivity to serotonergic medicines

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

An economy in transition: Costs of pension reform in an overlapping generations model

Ageing, as a phenomenon, is slowly becoming a much debated topic of research by pension reform authorities of differing economics. Neither industrialized nor developing economies is immune to the impending ageing phenomenon that is predicted by the United Nations (UN) Population Report to reach its peak by 2050. Authors have been consistent in forwarding the idea of pension reforms to economies that are struggling with the financial sustainability of their traditional Pay-As-You-Go (PAYG) system. Modern pension systems such as Mixed and Fully Funded pension systems have been determined suitable by comparing the steady state welfare effects that an economy might achieve under either of the concerned the steady state welfare effects that an economy might achieve under either of the concerned pension system. Conveniently, from independent calculations using of the stylized overlapping generations model (OLG) under a closed economy framework, this paper has also arrived at the predominant conclusion that a Fully Funded pension system induces a greater positive welfare effect. There is however a lack of literature that takes into account the transitional costs inherent in pension reforms. Such cost considerations are crucial in helping economies strategize on the more cost-minimizing pension reform path to undertake. Hence, it has also been the goal of this paper to provide a theoretical framework that highlights transitional costs incurred by taking varying transition paths towards reaching a desired pension system. Through comparing aggregate costs of shifting, it is apparent that the PAYG-Mixed-Fully Funded pension system-a two tier pension reform path –showcases a less costly alternative compared to the single tiered PAYG-Fully Funded and Mixed-Fully Funded pension reform paths. In terms of providing policy makers with the right theoretical bases for making decisions concerning policy reforms, these findings can allow such economies to mitigate financial and social cost of transition

Low risk, high return: Exploring the outperformance of value and momentum-driven low-volatility equity portfolios

The volatility and perceived risks of the stock market have been deterring many people from investing in it, even if some still fall for get-rich-quick investment scams. Only less than 1% of the Philippine population have equity exposures. This study was conducted with the purpose of introducing low-volatility investing to the local market and possibly entice more people to invest, especially those who are risk-averse. The study was undertaken to determine the manifestation of the low-volatility anomaly in the Philippine stock market with CAPM beta as the measure of risk used. The researchers constructed and simulated beta quintile portfolios from July 1, 2006 to June 30, 2016. Book-to-price spread quintiles and the Carhart four-factor model were used to determine if the factors of value and momentum influenced the performance of the lowest beta quintile portfolio. The researchers found that the lowest-risk portfolio underperformed its higher-volatility peers and the benchmark, PSEi, which means that the relationship between risk and return is positive, failing to defy the concept of the risk-return tradeoff. The returns of the portfolio have a positive relationship with value and momentum, indicating influence. These relationships, however, were found to be statistically insignificant from zero. This study is the first locally-written literature that explores the potential of a low-risk strategy to generate outperformance in the financial markets

Impact of the coronavirus disease 2019 pandemic on irritable bowel syndrome

Background and aim: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. Methods: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. Results: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. Conclusion: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS