Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus.

Changes in the expression of ion channels, contributing to altered neuronal excitability, are emerging as possible mechanisms in the development of certain human epilepsies. In previous immature rodent studies of experimental prolonged febrile seizures, isoform-specific changes in the expression of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCNs) correlated with long-lasting hippocampal hyperexcitability and enhanced seizure susceptibility. Prolonged early-life seizures commonly precede human temporal lobe epilepsy (TLE), suggesting that transcriptional dysregulation of HCNs might contribute to the epileptogenic process. Therefore, we determined whether HCN isoform expression was modified in hippocampi of individuals with TLE. HCN1 and HCN2 expression were measured using in situ hybridization and immunocytochemistry in hippocampi from three groups: TLE with hippocampal sclerosis (HS; n = 17), epileptic hippocampi without HS, or non-HS (NHS; n = 10), and autopsy material (n = 10). The results obtained in chronic human epilepsy were validated by examining hippocampi from the pilocarpine model of chronic TLE. In autopsy and most NHS hippocampi, HCN1 mRNA expression was substantial in pyramidal cell layers and lower in dentate gyrus granule cells (GCs). In contrast, HCN1 mRNA expression over the GC layer and in individual GCs from epileptic hippocampus was markedly increased once GC neuronal density was reduced by >50%. HCN1 mRNA changes were accompanied by enhanced immunoreactivity in the GC dendritic fields and more modest changes in HCN2 mRNA expression. Furthermore, similar robust and isoform-selective augmentation of HCN1 mRNA expression was evident also in the pilocarpine animal model of TLE. These findings indicate that the expression of HCN isoforms is dynamically regulated in human as well as in experimental hippocampal epilepsy. After experimental febrile seizures (i.e., early in the epileptogenic process), the preserved and augmented inhibition onto principal cells may lead to reduced HCN1 expression. In contrast, in chronic epileptic HS hippocampus studied here, the profound loss of interneuronal and principal cell populations and consequent reduced inhibition, coupled with increased dendritic excitation of surviving GCs, might provoke a "compensatory" enhancement of HCN1 mRNA and protein expression

Online health-conscious energy management strategy for a hybrid multi-stack fuel cell vehicle based on game theory

The use of multiple low-power fuel cells (FCs), instead of a high-power one, in the powertrain of a FC-hybrid electric vehicle (FC-HEV) has recently received considerable attention. This is mainly due to the fact that this configuration can lead to higher efficiency, durability, and reliability. However, the added degrees of freedom require an advanced multi-agent energy management strategy (EMS) for an effective power distribution among power sources. This paper puts forward an EMS based on game theory (GT) for a multi-stack FCHEV with three FCs and a battery pack. GT is a well-approved method for characterizing the interactions in multiagent systems. Unlike the other strategies, the proposed EMS is equipped with an online identification system to constantly update the time-varying characteristics of the power sources. The performance of the suggested strategy is investigated through two case studies. Firstly, a comparative study with two other EMSs, dynamic programming (offline), and a competent rule-based strategy (online), is conducted to realize the capability of GT. Secondly, to justify the necessity of online system identification, the degradation effect of each power source on the EMS performance is examined. The carried-out studies show that the total cost (hydrogen consumption and degradation) of the proposed strategy is almost 6% better than the rule-based EMS while keeping a reasonable difference with dynamic programming. Moreover, health unawareness of power sources can increase the hydrogen consumption up to 7% in the studied system

Consumer Perspectives on Access to Directâ toâ Consumer Genetic Testing: Role of Demographic Factors and the Testing Experience

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137391/1/milq12262.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137391/2/milq12262_am.pd

Teaching Medical Students to Help Patients Manage Their Weight: Outcomes of an Eight-School Randomized Controlled Trial

BACKGROUND: Given the rising rates of obesity there is a pressing need for medical schools to better prepare students for intervening with patients who have overweight or obesity and for prevention efforts. OBJECTIVE: To assess the effect of a multi-modal weight management curriculum on counseling skills for health behavior change. DESIGN: A pair-matched, group-randomized controlled trial (2015-2020) included students enrolled in eight U.S. medical schools randomized to receive either multi-modal weight management education (MME) or traditional weight management education (TE). SETTING/PARTICIPANTS: Students from the class of 2020 (N=1305) were asked to participate in an objective structured clinical examination (OSCE) focused on weight management counseling and complete pre and post surveys. A total of 70.1% of eligible students (N=915) completed the OSCE and 69.3% (N=904) completed both surveys. INTERVENTIONS: The MME implemented over three years included a web-based course, a role-play classroom exercise, a web-patient encounter with feedback, and an enhanced clerkship experience with preceptors trained in weight management counseling (WMC). Counseling focused on the 5As (Ask, Advise, Assess, Assist, Arrange) and patient-centeredness. MEASUREMENTS: The outcome was student 5As WMC skills assessed using an objective measure, an OSCE, scored using a behavior checklist, and a subjective measure, student self-reported skills for performing the 5As. RESULTS: Among MME students who completed two of three WMC components compared to those who completed none, exposure was significantly associated with higher OSCE scores and self-reported 5A skills. LIMITATIONS: Variability in medical schools requiring participation in the WMC curriculum. CONCLUSIONS: This trial revealed that medical students struggle with delivering weight management counseling to their patients who have overweight or obesity. Medical schools, though restrained in adding curricula, should incorporate should incorporate multiple WMC curricula components early in medical student education to provide knowledge and build confidence for supporting patients in developing individualized plans for weight management. NIH TRIAL REGISTRY NUMBER: R01-194787

Solubility of Anthracene in Binary and Ternary Mixtures of Cyclohexanone, Ethyl Acetate, and Methanol at 298.2 K

This article discusses the solubility of anthracene in binary and ternary mixtures of cyclohexanone, ethyl acetate, and methanol at 298.2 K

Solubility of Anthracene in C1-C3 Alcohols from (298.2 to 333.2) K and Their Mixtures with 2-Propanone at 298.2 K

Article discussing the solubility of anthracene in C1-C3 alcohols from (298.2 to 333.2) K and their mixtures with 2-propanone at 298.2 K