The Association of Body Mass Index and Early Outcomes Following Orthognathic Surgery.

BACKGROUND: The existing data on the link between body mass index (BMI), operative characteristics, and surgical outcomes across orthognathic surgery are limited. PURPOSE: The purpose was to measure the association between BMI and early postoperative outcomes in orthognathic surgery. STUDY DESIGN, SETTING, AND SAMPLE: This is a retrospective cohort study of patients (n = 118) aged > 14 years undergoing bimaxillary orthognathic surgery between 2015 and 2018 by a single surgeon within the Kaiser Permanente Northern California-integrated healthcare system. Patients undergoing unilateral or additional procedures, history of prior orthognathic surgery, or pre-existing pain conditions were excluded. PREDICTOR VARIABLE: The predictor variable was BMI measured as a continuous (kg/m2) and categorical variable (underweight/normal, overweight, obese). MAIN OUTCOME VARIABLE(S): The primary outcome variables were additional postoperative antibiotics, increased postoperative visits, wound dehiscence, and wound infection. The secondary outcome variables were total operative and anesthesia time. COVARIATES: The demographic covariates included age, sex, and race/ethnicity. The clinical covariates included history of obstructive sleep apnea, Mallampati score, tobacco use, American Society of Anesthesia classification, thyromental distance, history of difficult intubation, and Angle's classification. ANALYSES: Bivariate and multivariate analyses were performed to measure the associations between BMI and the primary and secondary outcomes. Multivariable logistic regression analyses were used to measure associations between BMI and the postoperative outcomes. Statistical significance was defined as P < .05. RESULTS: The study sample was composed of 118 subjects with a mean age of 26.91 years (standard deviation 9.43). Forty-seven percent (n = 55) were male, and the mean BMI was 25.13 (standard deviation 5.19). BMI category was significantly associated with age, with increasing age associated with higher BMI category (P = .02). According to the bivariate and multivariable logistic regression analyses, controlling for age, race/ethnicity, BMI, and total operative time, increased total operative time was associated with additional postoperative antibiotics (odds ratio = 1.03, 95% confidence interval: 1.01, 1.05), and increased postoperative appointments (odds ratio = 1.02, 95% confidence interval: 1.01, 1.04). No significant association between BMI and other clinical or operative characteristics was seen aside from American Society of Anesthesia classification. CONCLUSION AND RELEVANCE: Elevated BMI was not associated with worsened operative characteristics or postoperative outcomes. This supports the suitability of orthognathic surgery in a BMI-diverse population.

Sex-specific peripheral and central responses to stress-induced depression and treatment in a mouse model.

Major depressive disorder affects ~20% of the world population and is characterized by strong sexual dimorphism with females being two to three times more likely to develop this disorder. Previously, we demonstrated that a combination therapy with dihydrocaffeic acid and malvidin-glucoside to synergistically target peripheral inflammation and stress-induced synaptic maladaptation in the brain was effective in alleviating chronic social defeat stress (CSDS)-induced depression-like phenotype in male mice. Here, we test the combination therapy in a female CSDS model for depression and compared sex-specific responses to stress in the periphery and the central nervous system. Similar to male mice, the combination treatment is also effective in promoting resilience against the CSDS-induced depression-like behavior in female mice. However, there are sex-specific differences in peripheral immune responses and differential gene regulation in the prefrontal cortex to chronic stress and to the treatment. These data indicate that while therapeutic approaches to combat stress-related disorders may be effective in both sexes, the mechanisms underlying these effects differ, emphasizing the need for inclusion of both sexes in preclinical studies using animal models.

Peripheral and cognitive benefits of physical exercise in a mouse model of midlife metabolic syndrome.

Despite national and international efforts for the prevention of metabolic syndrome and its underlying diseases/disorders, its prevalence is still rising, especially in the middle-aged population. In this study, we explore the effect of high fat diet on the development of metabolic syndrome in middle-aged mice and to evaluate the potential benefits of voluntary physical exercise on the periphery as well as brain cognitive function, and to explore the potential mechanisms. We found that metabolic syndrome developed at middle age significantly impairs cognitive function and the impairment is associated with gene dysregulation in metabolic pathways that are largely affecting astrocytes in the brain. Eight-week voluntary wheel running at a frequency of three times a week, not only improves peripheral glucose control but also significantly improves learning and memory. The improvement of cognitive function is associated with restoration of gene expression involved in energy metabolism in the brain. Our study suggests that voluntary physical exercise is beneficial for metabolic syndrome-induced peripheral as well as cognitive dysfunction and can be recommended as therapeutic intervention for metabolic syndrome and associated diseases.

Development of grape polyphenols as multi-targeting strategies for Alzheimer's disease.

Alzheimer's disease (AD) is by far the most prevalent neurodegenerative disease of aging and is a major burden for patients, caregivers, and the overall health care system. The complexity of AD pathophysiology and the lack of deep understanding of disease mechanisms impeded the development of AD therapy. Currently approved treatments for AD only modestly improve cognitive function but do not modify disease course. The lack of pharmacological approaches has led to the consideration of alternative strategies to prevent or to slow down the progression of AD. There has been a growing interest in the scientific community regarding the impact of diet and nutrition on AD. Grape derived nutraceuticals and phytochemical compounds have demonstrated anti-amyloidogenic, antioxidative, anti-inflammatory and neurotrophic properties and present as potential novel strategies for AD treatment. In this review, we summarize promising grape derived polyphenols that have been shown to modulate AD pathophysiology including amyloid plaques and neurofibrillary tangles formation, AD-induced oxidative stress, neuroinflammation and synaptic dysfunction.

SUMO E3 ligase PIAS1 is a potential biomarker indicating stress susceptibility.

Prior studies suggest that individual differences in stress responses contribute to the pathogenesis of neuropsychiatric disorders. In the present study, we investigated the role of small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) in mediating stress responses to chronic social defeat stress (CSDS). We found that mRNA and protein levels of PIAS 1 were decreased in the hippocampus of high-susceptibility (HS) mice but not in low-susceptibility (LS) mice after CSDS. Local overexpression of PIAS1 in the hippocampus followed by CSDS exposure promoted stress resilience by attenuating social avoidance and improving anxiety-like behaviors. Viral-mediated gene transfer to generate a conditional knockdown of PIAS1 in the hippocampus promoted social avoidance and stress vulnerability after subthreshold microdefeat. HS mice displayed decreased levels of glucocorticoid receptor (GR) expression, and GR SUMOylation in the hippocampus was associated with stress vulnerability. Furthermore, cytokine/chemokine levels were changed predominantly in the hippocampus of HS mice. These results suggest that hippocampal PIAS1 plays a role in the regulation of stress susceptibility by post-translational modification of GRs.