The astroglial gap junctional network formed by connexin (Cx) channels plays a central role in regulating neuronal activity and network synchronization. However, its involvement in the development and progression of epilepsy is not yet understood.  https://www.selleckchem.com/products/gcn2ib.html  Loss of interastrocytic gap junction (GJ) coupling has been observed in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy (MTLE) and in mouse models of MTLE, leading to the suggestion that it plays a causative role in the pathogenesis. To further elucidate this clinically relevant question, we investigated consequences of astrocyte disconnection on the time course and severity of kainate-induced MTLE with hippocampal sclerosis (HS) by comparing mice deficient for astrocytic Cx proteins with wild-type mice (WT). Continuous telemetric EEG recordings and video monitoring performed over a period of 4 weeks after epilepsy induction revealed substantially higher seizure and interictal spike activity during the chronic phase in Cx deficient versus WT mice, while the severity of status epilepticus was not different. Immunohistochemical analysis showed that, despite the elevated chronic seizure activity, astrocyte disconnection did not aggravate the severity of HS. Indeed, the extent of CA1 pyramidal cell loss was similar between the experimental groups, while astrogliosis, granule cell dispersion, angiogenesis, and microglia activation were even reduced in Cx deficient as compared to WT mice. Interestingly, seizure-induced neurogenesis in the adult dentate gyrus was also independent of astrocytic Cxs. Together, our data indicate that constitutive loss of GJ coupling between astrocytes promotes neuronal hyperexcitability and attenuates seizure-induced histopathological outcomes. © 2020 The Authors. Glia published by Wiley Periodicals, Inc.OBJECTIVES With high numbers of persons with dementia living in residential care, it is vital to maximize psychosocial well-being for this population in this setting. The current study observed whether proportions of positive affect in residents differed based on co-occurring staff (typically certified nurse assistants) interaction types. METHODS A trained research team observed staff/resident interactions and affect in residents with dementia in common areas of a residential memory care unit (n = 22; observations over one year, or 6999 minutes total). RESULTS The most observed resident affect type was neutral (53.1% of all minutes observed), followed by positive affect (44.5%). The most common staff interaction type was neutral/no interaction (81.1% of all minutes observed), followed by positive staff interactions (18.1%). There was very little resident negative affect (2.4%) and staff negative interactions (.8%) observed. When staff had neutral/no/negative interactions, residents were positive 36% of the time, whereas when staff had positive interactions with them, residents were positive 81% of the time (z = 28.84, p  less then  .001). A qualitative review of field notes identified themes and subthemes providing a more thorough understanding and context for the resident affect and staff interactions. While quantitative analyses suggested low rates of negative staff interaction, field notes highlight that neutral or no interactions with residents sometimes comprised missed opportunities, as well as more problematic lack of interaction (ignoring). CONCLUSIONS Not just avoiding negative interactions, but eliciting positive social interactions between staff and residents is important in promoting positive affect and overall wellbeing in persons with dementia. © 2020 John Wiley & Sons Ltd.In allometric studies, the joint distribution of the log-transformed morphometric variables is typically elliptical and with heavy tails. To account for these peculiarities, we introduce the multivariate shifted exponential normal (MSEN) distribution , an elliptical heavy-tailed generalization of the multivariate normal (MN). The MSEN belongs to the family of MN scale mixtures (MNSMs) by choosing a convenient shifted exponential as mixing distribution. The probability density function of the MSEN has a simple closed-form characterized by only one additional parameter, with respect to the nested MN, governing the tail weight. The first four moments exist and the excess kurtosis can assume any positive value. The membership to the family of MNSMs allows us a simple computation of the maximum likelihood (ML) estimates of the parameters via the expectation-maximization (EM) algorithm; advantageously, the M-step is computationally simplified by closed-form updates of all the parameters. We also evaluate the existence of the ML estimates. Since the parameter governing the tail weight is estimated from the data, robust estimates of the mean vector of the nested MN distribution are automatically obtained by downweighting; we show this aspect theoretically but also by means of a simulation study. We fit the MSEN distribution to multivariate allometric data where we show its usefulness also in comparison with other well-established multivariate elliptical distributions. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIM Stress echocardiography (SE) with state-of-the-art imaging protocol allows a comprehensive assessment of regional wall-motion abnormalities and Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD). We sought to assess the variables potentially impacting on success rate of SE with CFVR. METHODS AND RESULTS In a single-center, prospective, observational study design, from 2007 to 2019, we enrolled 2989 consecutive patients (age 67 ± 12 years; 1723 men) referred for SE, without contrast, for chronic known (n = 1130) or suspected (n = 1859) coronary syndromes. Coronary flow velocity reserve was measured as stress/rest peak diastolic flow velocity. The same operator (LC) performed all examinations with the same machine (GE Vivid 7). Interpretable CFVR was obtained in 2808 patients (feasibility = 93.9%). Overall success rate was lowest (91.4%) in 2007-2008 and steadily rose to 97.8% in 2017-2019 (P for trend less then .0001). Feasibility was excellent for men (93.7%) and women (94.