Stress exacerbates neuron loss and microglia proliferation in a rat model of excitotoxic lower motor neuron injury.

All individuals experience stress and hormones (e.g., glucocorticoids/GCs) released during stressful events can affect the structure and function of neurons. These effects of stress are best characterized for brain neurons; however, the mechanisms controlling the expression and binding affinity of glucocorticoid receptors in the spinal cord are different than those in the brain. Accordingly, whether stress exerts unique effects on spinal cord neurons, especially in the context of pathology, is unknown. Using a controlled model of focal excitotoxic lower motor neuron injury in rats, we examined the effects of acute or chronic variable stress on spinal cord motor neuron survival and glial activation. New data indicate that stress exacerbates excitotoxic spinal cord motor neuron loss and associated activation of microglia. In contrast, hypertrophy and hyperplasia of astrocytes and NG2+ glia were unaffected or were modestly suppressed by stress. Although excitotoxic lesions cause significant motor neuron loss and stress exacerbates this pathology, overt functional impairment did not develop in the relevant forelimb up to one week post-lesion. These data indicate that stress is a disease-modifying factor capable of altering neuron and glial responses to pathological challenges in the spinal cord.

Year in Review 2021: Noteworthy Literature in Cardiothoracic Anesthesia.

In 2021, progress in clinical science related to Cardiac Anesthesiology continued, but at a slower rate due to the ongoing pandemic and disruptions to clinical research. Most progress was incremental and addressed persistent questions related to our field. To identify articles for this review, we completed a structured review using our previously reported methods (1). Specifically, we used the search terms: "cardiac anesthesiology and outcomes" (n = 177), "cardiothoracic anesthesiology" (n = 34), "cardiac anesthesia," and "clinical outcomes" (n = 42) filtered on clinical trials and the year 2021 in PubMed. We also reviewed clinical trials from the most prominent clinical journals to identify additional studies for a narrative review. We then selected the most noteworthy publications for inclusion in this review and identified key themes.

Year in Review 2020: Noteworthy Literature in Cardiothoracic Anesthesiology.

The year 2020 was marred by the emergence of a deadly pandemic that disrupted every aspect of life. Despite the disruption, notable research accomplishments in the practice of cardiothoracic anesthesiology occurred in 2020 with an emphasis on optimizing care, improving outcomes, and expanding what is possible for patients undergoing cardiac surgery. This year's edition of Noteworthy Literature Review will focus on specific themes in cardiac anesthesiology that include preoperative anemia, predictors of acute kidney injury following cardiac surgery, pain management modalities, anticoagulation strategies after transcatheter aortic valve replacement, mechanical circulatory support, and future directions in research.

Integrating a Cadaver Review Session into the Existing Regional Anesthesia Training for Anesthesiology Residents: An Initial Experience.

The Department of Anesthesiology's Acute Pain Service (APS) places ultrasound-guided peripheral nerve blocks (PNBs) to manage acute peri-operative pain. PNB success is dependent on detailed anatomical knowledge which residents may not have formally reviewed since medical school. This study describes the integration of a cadaver review session (CRS) that reintroduces PNB-related anatomy into the existing APS rotation. During each CRS, an anatomist reviewed the major nerve and surrounding structures, while an APS attending integrated the anatomy with PNB techniques. During the pilot, 1st- and 3rd-year clinical anesthesia (CA) residents (9 CA1s, 7 CA3s) completed pre- and post-session surveys and rated the CRS's perceived value and impact on self-confidence with anatomical knowledge. Following the pilot, an additional 17 CA1s and 9 CA3s participated in the CRS and completed post-session surveys. Descriptive statistics were used to summarize responses and unpaired t tests were used to compare pre- and post-session responses and responses between cohorts. All participants were overwhelmingly positive about the CRS and its value to the APS rotation, with 98% agreeing they recommend the CRS and found it accessible. Residents believed participation would improve board exam (average = 4.83 ± 0.66) and clinical performance (average = 4.86 ± 0.65), and self-reported increases in confidence with anatomical knowledge. Residents in the pilot group reported significantly greater confidence (p < 0.01) in their perceived anatomical knowledge after the CRS. The CRS positively impacted resident confidence in their anatomical knowledge and perceived ability to identify anatomical structures. Residents reported the CRS was a highly valued addition to regional anesthesia training.

Evaluation of wastewater tracers to predict pharmaceutical distributions and behavior in the Long Island Sound estuary.

Urban estuaries receive large volumes of effluents from municipal wastewater treatment facilities containing numerous contaminants, such as pharmaceuticals residues. Water was sampled for 16 highly prescribed pharmaceuticals at 17 sites along the Long Island Sound (LIS) estuary located in the Northeastern U.S. Pharmaceutical concentrations were highest in western LIS, ranging from non-detect to 71 ng L-1 and declining steadily eastward, while river samples from four major tributaries ranged from non-detect to 83 ng L-1. Two tracers, sucralose and caffeine, accurately predicted pharmaceutical behavior in LIS while only sucralose was effective at the river sites. Sucralose also tracked well with the salinity gradient in LIS, exhibiting conservative behavior along the transect. Attenuation factors were determined for measurable pharmaceuticals and compared against sucralose to estimate the magnitude of decline in concentrations that may be attributable to in situ degradation and partitioning. The results demonstrate sucralose's effectiveness as a tracer of wastewater-borne contaminants under estuarine conditions.

Association of mouse Dlg4 (PSD-95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams' syndrome.

OBJECTIVE: Research is increasingly linking autism spectrum disorders and other neurodevelopmental disorders to synaptic abnormalities ("synaptopathies"). PSD-95 (postsynaptic density-95, DLG4) orchestrates protein-protein interactions at excitatory synapses and is a major functional bridge interconnecting a neurexinneuroligin-SHANK pathway implicated in autism spectrum disorders. METHOD: The authors characterized behavioral, dendritic, and molecular phenotypic abnormalities relevant to autism spectrum disorders in mice with PSD-95 deletion (Dlg4⁻(/)⁻). The data from mice led to the identification of single-nucleotide polymorphisms (SNPs) in human DLG4 and the examination of associations between these variants and neural signatures of Williams' syndrome in a normal population, using functional and structural neuroimaging. RESULTS: Dlg4⁻(/)⁻ showed increased repetitive behaviors, abnormal communication and social behaviors, impaired motor coordination, and increased stress reactivity and anxiety-related responses. Dlg4⁻(/)⁻ had subtle dysmorphology of amygdala dendritic spines and altered forebrain expression of various synaptic genes, including Cyln2, which regulates cytoskeletal dynamics and is a candidate gene for Williams' syndrome. A signifi-cant association was observed between variations in two human DLG4 SNPs and reduced intraparietal sulcus volume and abnormal cortico-amygdala coupling, both of which characterize Williams' syndrome. CONCLUSIONS: These findings demonstrate that DLG4 gene disruption in mice produces a complex range of behavioral and molecular abnormalities relevant to autism spectrum disorders and Williams' syndrome. The study provides an initial link between human DLG4 gene variation and key neural endophenotypes of Williams' syndrome and perhaps corticoamygdala regulation of emotional and social processes more generally.