Abstract Substance abuse typically begins in adolescence; therefore, the impact of alcohol during this critical time in brain development is of particular importance. Epidemiological data indicate ...that excessive alcohol consumption is prevalent among adolescents and may have lasting neurobehavioral consequences. Loss of cholinergic input to the forebrain has been demonstrated following fetal alcohol exposure and in adults with Wernicke–Korsakoff syndrome. In the present study, immunohistochemistry for choline acetyltransferase (ChAT) was determined to assess forebrain cholinergic neurons (Ch1-4), and behavioral changes following periadolescent alcohol exposure. Wistar rats were exposed to intermittent ethanol vapor (14 h on/10 h off/day) for 35 days from postnatal day (PD) 22 to PD 57 (average blood alcohol concentration (BAC): 163 mg%). Rats were withdrawn from vapor and assessed for locomotor activity, startle response, conflict behavior in the open field, and immobility in the forced swim test, as adults. Rats were then sacrificed at day 71/72 and perfused for histochemical analyses. Ethanol vapor–exposed rats displayed: increased locomotor activity 8 h after the termination of vapor delivery for that 24 h period at day 10 and day 20 of alcohol vapor exposure, significant reductions in the amplitude of their responses to prepulse stimuli during the startle paradigm at 24 h withdrawal, and at 2 weeks following withdrawal, less anxiety-like and/or more “disinhibitory” behavior in the open field conflict, and more immobility in the forced swim test. Quantitative analyses of ChAT immunoreactivity revealed a significant reduction in cell counts in the Ch1-2 and Ch3-4 regions of the basal forebrain in ethanol vapor–exposed rats. This reduction in cell counts was significantly correlated with less anxiety-like and/or more “disinhibitory” behavior in the open field conflict test. These studies demonstrate that behavioral measures of arousal, affective state, disinhibitory behavior, and ChAT+IR, are all significantly impacted by periadolescent ethanol exposure and withdrawal in Wistar rats.
Abstract Substantial evidence suggests that glutamatergic neurotransmission is a critical mediator of the experience-dependent synaptic plasticity that may underlie alcohol dependence. Substance ...abuse typically begins in adolescence; therefore, the impact of alcohol on glutamatergic systems during this critical time in brain development is of particular importance. The N-methyl- d -aspartate receptor (NMDAR) is involved in developmental mechanisms underlying neuronal differentiation and synaptogenesis and as such may be a target system for alcohol effects during adolescence. In the present study quantitative biochemical determinations were made of the relative abundance of different protein expressions of NMDAR subunits in adolescents and adults after 2 weeks of ethanol vapor exposure, and 24 h and 2 weeks following withdrawal. After 2 weeks of ethanol vapor exposure N-methyl- d -aspartate receptor NR1 subunit (NR1), N-methyl- d -aspartate receptor NR2A subunit (NR2A), and N-methyl- d -aspartate receptor NR2B subunit (NR2B) subunit expression was found to be increased in hippocampus of the adults. In contrast, 2 weeks of ethanol exposure resulted in no significant changes in NR1 and NR2B subunits and a reduction NR2A subunit expression in hippocampus in adolescents. Twenty-four h and 2 weeks following withdrawal from ethanol vapor NR1 and NR2A subunit expression in hippocampus was decreased in adolescents, whereas in adults it had returned to control levels. In frontal cortex, 2 weeks of chronic ethanol exposure produced decreases in NR1 subunit expression in both adults and adolescents but also produced decreases in NR2A and NR2B subunit expression in adults that returned or exceeded control levels by 2 weeks following withdrawal from ethanol vapor. These results demonstrate that NMDAR subunit composition can be modulated differentially between adolescents and adults by chronic ethanol exposure and withdrawal. These developmental differences in NMDAR subunits composition may also be associated with the enhanced vulnerability of the adolescent brain to ethanol dependence.
Exotic quantum states and fractionalized magnetic excitations, such as spinons in one-dimensional chains, are generally expected to occur in 3d transition metal systems with spin 1/2. Our ...neutron-scattering experiments on the 4f-electron metal Yb₂Pt₂Pb overturn this conventional wisdom. We observe broad magnetic continuum dispersing in only one direction, which indicates that the underlying elementary excitations are spinons carrying fractional spin-1/2. These spinons are the emergent quantum dynamics of the anisotropic, orbital-dominated Yb moments. Owing to their unusual origin, only longitudinal spin fluctuations are measurable, whereas the transverse excitations such as spin waves are virtually invisible to magnetic neutron scattering. The proliferation of these orbital spinons strips the electrons of their orbital identity, resulting in charge-orbital separation.
Purpose
Females suffer higher rates of operative recurrence and chronic pain following groin hernia repair. Guidelines recommend minimally invasive (MIS) groin hernia repair as the preferred approach ...to reduce these adverse outcomes. It is unknown what proportion of females receive MIS hernia repair. Therefore, our goal was to investigate adoption of evidence-based practices in groin hernia repair using sex as a biological variable.
Methods
Retrospective cohort study of adults undergoing elective groin hernia repair (2014–2019) within a statewide quality improvement collaborative. Primary outcome was surgical approach. Multivariable logistic regression was performed to analyze the likelihood of undergoing MIS hernia repair. Secondary outcomes were 30-day adjusted rates of clinical and patient-reported outcomes (PROs). PROs included regret to undergo surgery among patients who completed post-operative surveys.
Results
Among 23,723 patients, the majority (90.7%) were males. Compared to males, females less often underwent an MIS surgical approach (37.4% vs 45.1%,
p
< 0.0001). After adjustment for patient and clinical variables, females remained significantly less likely to undergo MIS groin hernia repair (aOR 0.88, 95% CI 0.80–0.97). Adjusted clinical outcomes were not different between males and females. Among 4325 patients who completed post-operative surveys, adjusted rates of regret to undergo surgery were higher among females (12.9% vs 8.5%,
p
= 0.003).
Conclusions
Even after adjusting for differences, females were less likely to receive guideline-concordant groin hernia repair and were more likely to regret surgery. Understanding the behaviors of surgeons who treat females with groin hernia may inform quality metrics to promote best practices in this population.
With the increased use of small self-complementary adeno-associated viral (AAV) vectors, the design of compact promoters becomes critical for packaging and expressing larger transgenes under ...ubiquitous or cell-specific control. In a comparative study of commonly used 800-bp cytomegalovirus (CMV) and chicken β-actin (CBA) promoters, we report significant differences in the patterns of cell-specific gene expression in the central and peripheral nervous systems. The CMV promoter provides high initial neural expression that diminishes over time. The CBA promoter displayed mostly ubiquitous and high neural expression, but substantially lower expression in motor neurons (MNs). We report the creation of a novel hybrid form of the CBA promoter (CBh) that provides robust long-term expression in all cells observed with CMV or CBA, including MNs. To develop a short neuronal promoter to package larger transgenes into AAV vectors, we also found that a 229-bp fragment of the mouse methyl-CpG-binding protein-2 (MeCP2) promoter was able to drive neuron-specific expression within the CNS. Thus the 800-bp CBh promoter provides strong, long-term, and ubiquitous CNS expression whereas the MeCP2 promoter allows an extra 570-bp packaging capacity, with low and mostly neuronal expression within the CNS, similar to the MeCP2 transcription factor.
Abstract Mouse models have been developed to simulate several relevant human traits associated with alcohol use and dependence. However, the neurophysiological substrates regulating these traits ...remain to be completely elucidated. We have previously demonstrated that differences in the event-related potential (ERP) responses can be found that distinguish high-alcohol preferring from low alcohol preferring mice that resemble differences seen in human studies of individuals with high and low risk for alcohol dependence. Recently, evidence of genes that affect event-related oscillations (EROs) and the risk for alcohol dependence has emerged, however, to date EROs have not been evaluated in genetic mouse models of high and low alcohol preference. Therefore, the objective of the present study was to characterize EROs in mouse models of high (C57BL/6 B6 and high alcohol preference 1 HAP-1 mice) and low (DBA/2J D2 and low alcohol preference-1 LAP-1 mice) alcohol preference. A time-frequency representation method was used to determine delta, theta and alpha/beta ERO energy and the degree of phase variation in these mouse models. The present results suggest that the decrease in P3 amplitudes previously shown in B6 mice, compared to D2 mice, is related to reductions in evoked delta ERO energy and delta and theta phase locking. In contrast, the increase in P1 amplitudes reported in HAP-1 mice, compared to LAP-1 mice, is associated with increases in evoked theta ERO energy. These studies suggest that differences in delta and theta ERO measures in mice mirror changes observed between groups at high- and low-risk for alcoholism where changes in EROs were found to be more significant than group differences in P3 amplitudes, further suggesting that ERO measures are more stable endophenotypes in the study of alcohol dependence. Further studies are needed to determine the relationship between expression of these neurophysiological endophenotypes and the genetic profile of these mouse models.
Although synaptic AMPA receptors have been shown to rapidly internalize, synaptic NMDA receptors are reported to be static. It is not certain whether NMDA receptor stability at synaptic sites is an ...inherent property of the receptor, or is due to stabilization by scaffolding proteins. In this study, we demonstrate that NMDA receptors are internalized in both heterologous cells and neurons, and we define an internalization motif, YEKL, on the distal C-terminus of NR2B. In addition, we show that the synaptic protein PSD-95 inhibits NR2B-mediated internalization, and that deletion of the PDZ-binding domain of NR2B increases internalization in neurons. This suggests an involvement for PSD-95 in NMDA receptor regulation and an explanation for NMDA receptor stability at synaptic sites.
Special Issue on quality in e-learning Ehlers, U.-D.; Hilera, J.R.
Journal of computer assisted learning,
02/2012, Letnik:
28, Številka:
1
Journal Article
Recenzirano
Quality is at the heart of education and training in all countries. Knowledge, information, and learning technologies are seen as a vital tool for achieving this. The promises of e‐learning are to ...open up our systems to the world, improve access for all, and increase learning effectiveness. In addition, knowledge, information, and learning technologies are seen as a catalyst for change in our efforts to reform and modernize education and training for an improved knowledge society.