Neuroprotective effects of flavonoids: endoplasmic reticulum as the target.

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.

Stroke Prevention in Blunt Cerebrovascular Injury: Role of Aspirin 81 mg.

BACKGROUND: The stroke rate in blunt cerebrovascular injury (BCVI) varies from 25% without treatment to less than 8% with antithrombotic therapy. There is no consensus on the optimal management to prevent stroke BCVI. We investigated the efficacy and safety of oral Aspirin (ASA) 81 mg to prevent BCVI-related stroke compared to historically reported stroke rates with ASA 325 mg and heparin. METHODS: A single-center retrospective study included adult trauma patients who received oral ASA 81 mg for BCVI management between 2013 and 2022. Medical records were reviewed for demographic and injury characteristics, imaging findings, treatment-related complications, and outcomes. RESULTS: Eighty-four patients treated with ASA 81 mg for BCVI were identified. The mean age was 41.50 years, and 61.9% were male. The mean Injury Severity Score and Glasgow Coma Scale were 19.82 and 12.12, respectively. A total of 101 vessel injuries were identified, including vertebral artery injuries in 56.4% and carotid artery injuries in 44.6%. Traumatic brain injury was found in 42.9%, and 16.7% of patients had a solid organ injur. Biffl grade I (52.4%) injury was the most common, followed by grade II (37.6%) and grade III (4.9%). ASA 81 mg was started in the first 24 hours in 67.9% of patients, including 20 patients with traumatic brain injury and 8 with solid organ injuries. BCVI-related stroke occurred in 3 (3.5%) patients with Biffl grade II (n = 2) and III (n = 1). ASA-related complications were not identified in any patient. The mean length of stay in the hospital was 10.94 days, and 8 patients died during hospitalization due to complications of polytrauma. Follow-up with computed tomography angiography was performed in 8 (9.5%) patients, which showed improvement in 5 and a stable lesion in 3 at a mean time of 58 days after discharge. CONCLUSIONS: In the absence of clear guidelines regarding appropriate medication, BCVI management should be individualized case-by-case through a multidisciplinary approach. ASA 81 mg is a viable option for BCVI-related stroke prevention compared to the reported stroke rates (2%-8%) with commonly used antithrombotics like heparin and ASA 325 mg. Future prospective studies are needed to provide insight into the safety and efficacy of the current commonly used agent in managing BCVI.

Tranexamic acid is not associated with a higher rate of thrombotic-related reintervention after major vascular injury repair.

BACKGROUND: Tranexamic acid (TXA) is associated with lower mortality and transfusion requirements in trauma patients, but its role in thrombotic complications associated with vascular repairs remains unclear. We investigated whether TXA increases the risk of thrombosis-related technical failure (TRTF) in major vascular injuries (MVI). METHODS: The PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from 2013 to 2022 for MVI repaired with an open or endovascular intervention. The relationship between TXA administration and TRTF was examined. RESULTS: The TXA group (n = 297) had higher rates of hypotension at admission (33.6% vs. 11.5%, p < 0.001), need for continuous vasopressors (41.4% vs. 18.4%, p < 0.001), and packed red blood cell transfusion (3.2 vs. 2.0 units, p < 0.001) during the first 24 hours compared with the non-TXA group (n = 1941), although demographics, injury pattern, and interventions were similar. Cryoprecipitate (9.1% vs. 2%, p < 0.001), and anticoagulant administration during the intervention (32.7% vs. 43.8%, p < 0.001) were higher in the TXA group; there was no difference in the rate of factor VII use between groups (1% vs. 0.7%, p = 0.485). Thrombosis-related technical failure was not different between the groups (6.3% vs. 3.8 p = 0.141) while the rate of immediate need for reoperation (10.1% vs. 5.7%, p = 0.006) and overall reoperation (11.4% vs. 7%, p = 0.009) was significantly higher in the TXA group on univariate analysis. There was no significant association between TXA and a higher rate of immediate need for reintervention (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.75-1.88; p = 0.465), overall reoperation rate (OR, 1.33; 95% CI, 0.82-2.17; p = 0.249) and thrombotic events in a repaired vessel (OR, 1.07; 95% CI, 0.60-1.92; p = 0.806) after adjusting for type of injury, vasopressor infusions, blood product and anticoagulant administration, and hemodynamics. CONCLUSION: Tranexamic acid is not associated with a higher risk of thrombosis-related technical failure in traumatic injuries requiring major vascular repairs. Further prospective studies to examine dose-dependent or time-dependent associations between TXA and thrombotic events in MVIs are needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

How cosmetic surgeons portray cosmetic procedures through Instagram? A content analysis on cosmetic surgeons' posts on Instagram.

The present study intends to explore the visual and textual content of posts cosmetic surgeons shared on Instagram pages in order to present their cosmetic surgical or non-surgical procedures. To do so, this study employed a qualitative approach using textual and visual content analysis on 200 Instagram posts shared by cosmetic surgeons. The results demonstrated that the content of analyzed posts can be categorized as 12 sub-themes which are clustered around four main themes; "You have got some body imperfections," "Body imperfections are worrisome," "Cosmetic procedure is the solution; we provide it for you" and "It's not a real surgery!."

Geriatric oral health competency among dental providers.

BACKGROUND: Geriatrics as an educational topic has been a high priority in current health care. The innovative Age-Friendly health system with the 4Ms structure (what Matters most, Medication, Mentation, Mobility) needs to be integrated into oral health and dental services training. The purpose of this study is to respond to one question: are the graduating general dentists trained and prepared to treat medically vulnerable elderly in communities? METHODS: All pre-doctorate dental students from first year to fourth year were invited to voluntarily respond to an online survey provided on Qualtrics. The survey provided examples of two broken molar teeth that need extraction. First, students were asked how comfortable they felt extracting the two molars based on the x-rays. Then, the question was repeated to evaluate if they felt comfortable with extracting the teeth in a patient with one chronic condition and related medication(s). Finally, the students were again questioned whether they feel comfortable to provide the same service to medically vulnerable patients with multiple health conditions and polypharmacy. RESULTS: The majority of students who participated in this study said they were comfortable with extracting the teeth of patients without any chronic condition. However, many more chose to refer medically vulnerable patients with multiple chronic conditions and polypharmacy to a specialist. CONCLUSIONS: Dental education in many U.S. dental schools may provide adequate education and create competent general dentists. Yet, the competency and confidence required for dentists to be able to treat older adults with multiple health conditions and using prescribed or over-the-counter medication is insufficient.

Abdominal Wall Thickness Predicts Surgical Site Infection in Emergency Colon Operations.

BACKGROUND: Body mass index (BMI) does not reliably predict Surgical site infections (SSI). We hypothesize that abdominal wall thickness (AWT) would serve as a better predictor of SSI for patients undergoing emergency colon operations. METHODS: We retrospectively evaluated our Emergency Surgery Database (2007-2018). Emergency colon operations for any indication were included. AWT was measured by pre-operative CT scans at 5 locations. Only superficial and deep SSIs were considered as SSI in the analysis. Univariate then multivariable analyses were used to determine predictors of SSI. RESULTS: 236 patients met inclusion criteria. The incidence of post-operative SSI was 25.8% and the median BMI was 25.8kg/m2 [22.5-30.1]. The median AWT between patients with and without SSI was significantly different (2.1cm [1.4, 2.8] and 1.8cm [1.2, 2.5], respectively). A higher BMI trended toward increased rates of SSI, but this was not statistically significant. In overweight (BMI 25-29.9kg/m2) and obese (BMI ≥30kg/m2) patients, SSI versus no SSI rates were (50.0% versus 41.9% and 47.4% versus 36.4%, P = 0.365 and 0.230) respectively. The incidence of SSI in patients with an average AWT < 1.8cm was 20% and 30% for patients with average AWT ≥1.8cm. On multivariable analysis, AWT ≥1.8cm at 2cm inferior to umbilicus was an independent predictor of SSI (OR 2.98, 95%CI 1.34-6.63, P = 0.007). CONCLUSIONS: AWT is a better predictor of SSI than BMI. Preoperative imaging of AWT may direct intraoperative decisions regarding wound management. Future clinical outcomes research in emergency surgery should include abdominal wall thickness as an important patient variable.

Where Did All the Appendicitis Go? Impact of the COVID-19 Pandemic on Volume, Management, and Outcomes of Acute Appendicitis in a Nationwide, Multicenter Analysis.

Objective: The study objective was to evaluate effects of the COVID-19 pandemic on rates of emergency department (ED) acute appendicitis presentation, management strategies, and patient outcomes. Summary Background Data: Acute appendicitis is the most commonly performed emergency surgery in the United States and is unlikely to improve without medical or surgical intervention. Dramatic reductions in ED visits prompted concern that individuals with serious conditions, such as acute appendicitis, were deferring treatment for fear of contracting COVID-19. Methods: Patients from 146 hospitals with diagnosed appendicitis and arrival between March 2016 and May 2020 were selected. Electronic medical records data were retrospectively reviewed to retrieve patient data. Daily admissions were averaged from March 2016 through May 2019 and compared with March 2020. April-specific admissions were compared across the 5-year pre-COVID-19 period to April 2020 to identify differences in volume, demographics, disease severity, and outcomes. Results: Appendicitis patient admissions in 2020 decreased throughout March into April, with April experiencing the fewest admissions. April 2020 experienced a substantial decrease in patients who presented with appendicitis, dropping 25.4%, from an average of 2030 patients (2016-2019) to 1516 in 2020. An even greater decrease of 33.8% was observed in pediatric patients (age <18). Overall, 77% of the 146 hospitals experienced a reduction in appendicitis admissions. There were no differences between years in percent of patients treated nonoperatively (P = 0.493) incidence of shock (P = 0.95), mortality (P = 0.24), or need for postoperative procedures (P = 0.81). Conclusions: Acute appendicitis presentations decreased significantly during the COVID-19 pandemic, while overall management and patient outcomes did not differ from previous years. Further research is needed focusing on putative explanations for decreased hospital presentations unrelated to COVID-19 infection and possible implications for surgical management of uncomplicated acute appendicitis.Keywords: acute appendicitis, COVID-19, decreasing volumes, multicenter study.

A Pilot Study of an Interprofessional Program Involving Dental, Medical, Nursing, and Pharmacy Students.

Objective: The silent epidemic of oral diseases disproportionately affects disadvantaged communities, especially the elderly who have complex needs for healthcare. This study was to evaluate a pilot oral health interprofessional program that provided hands-on experiences for students across four disciplines: dentistry, medicine, nursing, and pharmacy. Methods: The 8-weeks program was built on four pedagogical principles: care, critical thinking, communication, and collaboration coupled with the 4Ms model: what matters, medication, mentation, and mobility. The curriculum contained four scenarios of a dental complication in an elderly: Alzheimer's Disease, oral cancer, Parkinson's Disease, and stroke. A mixed-methods approach was used to evaluate this pilot program. Results: The average score of knowledge and attitude has increased from 2.94 to 4.39 (p < 0.05) on a 5-point Likert scale. The qualitative responses also showed that students became more confident in practicing within the Age-Friendly health system. Discussion: By the end of the program, all students recognized the significance of the interprofessional program to improve their knowledge and skills to work with professionals across disciplines. Two key features that contributed to the success of the program were (1) an interprofessional education that increased students' awareness of other types of services and (2) four scenarios that allowed students to solve the case and gain hands-on experience. Conclusion: An interprofessional education may equip students with competence to address the health of geriatric patients. Materials used in this study could be shared and adapted to prepare learners for other scenarios that require interprofessional team practice.

Steps towards validation of the Dental Education Clinical Learning Instrument (DECLEI) in American dental schools (DECLEI-USA).

PURPOSES/OBJECTIVES: Few tools assess the dental school clinical learning environment from students' perspectives. Considering previous efforts to validate the Dental Education Clinical Learning Instrument (DECLEI) in the United States, the goal of this study was to look for the fewest number of items that accounted for the most amount of variability in responses and/or had the highest correlation to the total DECLEI score using a larger, multi-center sample. METHODS: The DECLEI was distributed to 286 students in two dental schools (University of Iowa and University of Texas at Houston) during the 2017-2018 academic year. Two alternative methods were applied. In the first approach, all 24-items were regressed on the total composite score using a forward conditional method. In the second approach, the item-total correlation for the full scale was calculated and then items with relatively poor coefficients were eliminated. A cutoff of 0.30 or less was used. RESULTS: The first approach, Total R2 by Regression Model, produced a 9-item scale accounting for 90% of the variance in total score and a Cronbach's α coefficient of 0.79. The second approach, Item-Total Correlation, produced a larger scale (20 items), as well as a higher Cronbach's α coefficient of 0.89. The instrument also presented appropriate sensitivity to measure differences between race groups and school of origin. CONCLUSION: DECLEI may have the potential to be used as an instrument to measure clinical learning environments for U.S. dental students using either a smaller, concise scale (Mini DECLEI-USA) or a larger (DECLEI-USA), more thorough scale.

The impact of race on choice of location for elective surgical care in New York city.

BACKGROUND: The "white-flight" phenomenon of the mid-20th century contributed to the perpetuation of residential segregation in American society. In light of recent reports of racial segregation in our healthcare system, could a contemporary "white-flight" phenomenon also exist? METHODS: The New York Statewide Planning and Research Cooperative System was used to identify all Manhattan and Bronx residents of New York city who underwent elective cardiothoracic, colorectal, general, and vascular surgeries from 2010 to 2016. Primary outcome was borough of surgical care in relation to patient's home borough. Multivariable analyses were performed. RESULTS: White patients who reside in the Bronx are significantly more likely than racial minorities to travel into Manhattan for elective surgical care, and these differences persist across different insurance types, including Medicare. CONCLUSIONS: Marked race-based differences in choice of location for elective surgical care exist in New York city. If left unchecked, these differences can contribute to furthering racial segregation within our healthcare system.

Estimating the return on investment from a health risk management program offered to small Colorado-based employers.

OBJECTIVE: To determine whether changes in health risks for workers in small businesses can produce medical and productivity cost savings. METHODS: A 1-year pre- and posttest study tracked changes in 10 modifiable health risks for 2458 workers at 121 Colorado businesses that participated in a comprehensive worksite health promotion program. Risk reductions were entered into a return-on-investment (ROI) simulation model. RESULTS: Reductions were recorded in 10 risk factors examined, including obesity (-2.0%), poor eating habits (-5.8%), poor physical activity (-6.5%), tobacco use (-1.3%), high alcohol consumption (-1.7%), high stress (-3.5%), depression (-2.3%), high blood pressure (-0.3%), high total cholesterol (-0.9%), and high blood glucose (-0.2%). The ROI model estimated medical and productivity savings of $2.03 for every $1.00 invested. CONCLUSIONS: Pooled data suggest that small businesses can realize a positive ROI from effective risk reduction programs.

A descriptive evaluation of CDC's LEAN Works! Leading employees to activity and nutrition--a Web-based employer tool for workplace obesity management.

PURPOSE: The study aim was to determine the utility of and satisfaction with a Centers for Disease Control and Prevention (CDC) Web-based employer tool, CDC's LEAN Works!, which provides evidence-based recommendations and promising practices for obesity prevention and control at worksites. DESIGN: This study examined employers' natural usage (i.e., without any study parameters on how, when, or how much to use the Web site and its resources) and impressions of the Web site. SETTING: Employers of varying sizes, industry types, and levels of maturity in offering obesity management programs and from both private and public sectors were recruited to participate in the study. PARTICIPANTS: A convenience sample of 29 employers enrolled to participate. METHOD: Participants were followed over a 12-month period. First impressions, bimonthly use of the Web site, and final assessments were collected using self-report surveys and individual interviews. Descriptive analyses were conducted. RESULTS: Almost all (96%) of participants reported a positive experience with the Web site, noting it provided a wealth of information. Most reported they planned to continue to use the Web site to develop (77%), implement (92%), and evaluate (85%) their obesity management programs. Aspects of the Web site that employers found valuable included a step-by-step implementation process, templates and toolkits, specific recommendations, and promising practices. CONCLUSION: CDC's LEAN Works! is a useful resource for employers wishing to develop and implement evidence-based workplace obesity prevention programs.

Ten modifiable health risk factors are linked to more than one-fifth of employer-employee health care spending.

An underlying premise of the Affordable Care Act provisions that encourage employers to adopt health promotion programs is an association between workers' modifiable health risks and increased health care costs. Employers, consultants, and vendors have cited risk-cost estimates developed in the 1990s and wondered whether they still hold true. Examining ten of these common health risk factors in a working population, we found that similar relationships between such risks and total medical costs documented in a widely cited study published in 1998 still hold. Based on our sample of 92,486 employees at seven organizations over an average of three years, $82,072,456, or 22.4 percent, of the $366,373,301 spent annually by the seven employers and their employees in the study was attributed to the ten risk factors studied. This amount was similar to almost a quarter of spending linked to risk factors (24.9 percent) in the 1998 study. High risk for depression remained most strongly associated with increased per capita annual medical spending (48 percent, or $2,184, higher). High blood glucose, high blood pressure, and obesity were strongly related to increased health care costs (31.8 percent, 31.6 percent, and 27.4 percent higher, respectively), as were tobacco use, physical inactivity, and high stress. These findings indicate ongoing opportunities for well-designed and properly targeted employer-sponsored health promotion programs to produce substantial savings.

Inhaled epoprostenol improves oxygenation in severe hypoxemia.

BACKGROUND: Epoprostenol (Flolan), an inhalational epoprostenol vasodilator, increases pulmonary arterial flow and decreases pulmonary pressures, thereby improving gas exchange and arterial oxygenation. We evaluated the benefits of inhaled epoprostenol as a less expensive alternative to nitric oxide in ventilated surgical intensive care patients with severe hypoxemia. METHODS: After institutional review board approval was obtained, the records of mechanically ventilated surgical intensive care unit patients who received epoprostenol as a therapy for severe hypoxia (SaO2 < 90%) in a tertiary care referral center were retrospectively reviewed. Initial PaO2/FIO2 (P/F) ratio and oxygen saturation were compared with values at 12 and 48 hours after the administration of epoprostenol. One-way repeated-measures analysis of variance compared improvements in oxygenation. Further subgroup analyses evaluated differences among trauma, nontrauma patient subgroups, time to initiation of epoprostenol, and age. RESULTS: During a 20 month-interval beginning February 2009, 36 patients (23 trauma and 13 nontrauma; age, 15-80 years) were treated. Epoprostenol significantly improved both P/F ratio and oxygen saturation in both trauma and nontrauma patients. Therewas no difference between subgroups. Larger improvements in P/F ratiowere seen when epoprostenolwas started within 7 days. Response between age groups did not differ significantly. Subgroup analysis of mortality (trauma, 60.9% vs. nontrauma, 61.5%) failed to show any differences. CONCLUSION: Treatment with inhaled epoprostenol improved gas exchange in severely hypoxemic surgical patients. Earlier intervention (within 7 days of intubation) was more efficacious at improving oxygenation.

Seven-year trends in employee health habits from a comprehensive workplace health promotion program at Vanderbilt University.

OBJECTIVE: To assess long-term changes in health risks for employees participating in Vanderbilt University's incentive-based worksite wellness program. METHODS: Descriptive longitudinal trends were examined for employees' health risk profiles for the period of 2003 to 2009. RESULTS: The majority of risk factors improved over time with the most consistent change occurring in physical activity. The proportion of employees exercising one or more days per week increased from 72.7% in 2003 to 83.4% in 2009. Positive annual, monotonic changes were also observed in percentage for nonsmokers and seat belt usage. Although the largest improvements occurred between the first two years, improvements continued without significant regression toward baseline. CONCLUSIONS: This 7-year evaluation, with high participation and large sample size, provides robust estimates of health improvements that can be achieved through a voluntary incentive-based wellness program.