Exercise and stress as modulators of neurocognitive aging

Exercise is emerging as a promising low-cost intervention to mitigate age-related memory decline and promote successful aging. Aerobic exercise training enhances cardiorespiratory fitness (CRF) and improves integrity of the medial temporal lobe (MTL) memory system. The hippocampus, a brain region located within the MTL, is critically involved in episodic and spatial memory formation, including spatial navigation, and demonstrates subfield-specific plasticity in response to aerobic exercise among both animals and young adult humans. Yet it remains unclear whether hippocampal subfield-specific exercise training and CRF effects also extend to older adults. Another modulator of structural and functional integrity of the MTL is chronic stress. Importantly, chronic stress was shown to predominantly impact brain regions such as the hippocampus and associated cognitive functions, including episodic memory, that are highly vulnerable to the effects of chronic stress and decline with age. Allostatic load (AL), or the integrative biological dysregulation of multiple biological systems resulting from chronic stress, is associated with poorer cognition, and reduced structural brain integrity. Black Americans were shown to have high burden of AL compared to non-Hispanic White Americans, and this was associated with reports of greater perceived discrimination, a salient psychosocial stressor, among the former group. Although race is a sociocultural construct, Black-White disparities exist in cognitive task performance, and risk of Alzheimer’s disease (AD) and dementia, with Black Americans displaying significantly worse cognitive task performance scores, and a greater likelihood to be diagnosed with AD and dementia compared to non-Hispanic White Americans. Thus, greater AL and discriminatory experiences in Black compared to non-Hispanic White older adults may underlie the racial disparity in neurocognitive aging. The goal of this dissertation was to examine the opposing impact of chronic stress and exercise on neurocognitive aging. This was accomplished by 1) investigating aerobic exercise intervention effects on hippocampal subfield volume and fMRI activity during spatial navigation, a complex cognitive function that declines with age and that is, in part, supported by the MTL (Project 1), 2) examining the effect of AL as a cumulative, physiological stress measure on neurocognitive aging (Project 2), and 3) examining the effect of chronic psychosocial stress through the lens of social discrimination on the functional connectivity of the MTL subsystem of the default mode network, a resting state network that has been linked to episodic memory (Project 3). The secondary aim of this dissertation was to look at the effect of AL (Project 2) and social discrimination (Project 3) on racial neurocognitive disparities in cognitively intact older Black and non-Hispanic White adults. In the first project, data from two randomized controlled clinical trials of aerobic exercise intervention targeting healthy, initially sedentary adults aged 55-85 years were used to examine the effect of exercise training and exercise-related CRF on the hippocampal integrity on the subfield level. Both randomized controlled trials randomly assigned participants to either: aerobic exercise group or active control group and underwent baseline and end-of-study fitness testing, cognitive testing, and high resolution structural and functional MRI. The first objective of this project aimed to test whether aerobic exercise training increases CRF level, which, in turn, increases anterior hippocampal subfield volume and/or attenuates volumetric decline among older adults undergoing aerobic exercise training compared to those in the active control group. Partially supporting our prediction, results displayed that following the period of the 12-week exercise intervention, the active control group but not the aerobic exercise group showed a right dentate gyrus (DG) head volumetric decline that was trending toward statistical significance. Additionally, a positive significant association between changes in CRF and left subiculum (SUB) head volume following the exercise intervention among women was found. The second objective sought to examine whether aerobic exercise intervention modulates the activation in the hippocampus in a subfield-specific manner during virtual reality navigation task performance, particularly modulating activation in the SUB subfield. Consistent with our structural results an increase in CRF was associated with a decrease fMRI activity in the left SUB. Whole-brain analysis during virtual reality navigation task performance showed that an increase in CRF was associated with a decrease in fMRI activity in the cuneus and right middle frontal gyrus, both brain regions that repeatedly display activation during virtual navigation. In the second project, existing data from the Framingham Heart Study (FHS) was used. Cognitively intact men and women, who identified as either Black or African American from the first multiracial Omni group 1 cohort (OMNI1), or White non-Hispanic from the second-generation cohort (Gen2), and were native English speakers, were included in the study. AL was calculated using the values for 10 biomarkers available in the FHS database for the two cohorts studied that are biomarkers for immune, metabolic, and cardiovascular system function. The objective of this project sought to test the prediction that AL correlates with cognitive function and brain structures, particularly hippocampal volume. We additionally sought to examine the secondary prediction that AL mediates the relationship between race and cognitive task performance and structural brain integrity, in age- sex- and education matched racial groups of cognitively intact older adults after controlling for quality of education, cardiovascular-related comorbidities and depression in the FHS cohorts. Results demonstrated that there was no significant correlation between AL and cognitive and brain volumetric measures, however there were significant Black-White disparities in cognitive task performance in verbal and visual learning and memory, abstract reasoning and attention span. These Black-White cognitive task performance disparities existed even after controlling for quality of education, and cardiovascular-related comorbidities. Although there was no significant racial disparity in the mean score of AL index, our physiological stress measure, AL partially explained the observed Black-White disparity in cognitive task performance in verbal learning and memory. Importantly the observed AL effect was not driven by the cardio-metabolic component biomarkers that are part of the AL index, known to overlap with cardiovascular risk factors, but rather, the AL index drove this effect as a whole. There were no racial disparities in brain volumetric measures after controlling for cardiovascular-related comorbidities. Furthermore, there were no sex differences in the effect of AL in any of our neurocognitive outcome measures. In the third project, cognitively intact older Black and White adults (aged 55-80 years) were recruited from the greater Boston area. To measure perceived social discrimination, participants were asked to complete the Experiences of Discrimination questionnaires. Additionally, participants underwent fMRI scanning to examine the functional connectivity of resting-state brain networks. This project sought to test the prediction that greater perceived everyday discrimination would be associated with alteration of resting state functional connectivity, particularly in the MTL subsystem. Results showed that greater perceived everyday discrimination predicted stronger resting-state connectivity between the MTL subsystem, and a cluster located in the right control network, suggesting that perceived discrimination, a psychosocial stressor, may cause functional alteration in brain networks supporting memory and cognitive control in older adults. In conclusion, findings of these studies suggest a neuroprotective effect of exercise, where exercise may attenuate aging-related decline in the structure and function of hippocampal subfields, especially among women, and possibly by targeting the SUB. Furthermore, findings of these studies suggest stress related mechanisms underlying neurocognitive integrity, particularly in the MTL memory system.

The psychometric properties of the Arabic version of the Satisfaction with Daily Occupations

Introduction: There is a shortage of tools designed for use by occupational therapy practice in Arabic-speaking countries. The purpose of this study was to translate and cross-culturally adapt the original Satisfaction with Daily Occupations tool to Arabic and assess the psychometric properties of the adapted tool. Method: A cross-cultural adaptation process was performed. Face, content, and criterion validity were examined, as well as internal consistency and test-retest reliability. The study included 147 healthy adults and 73 patients with cerebrovascular accident. They were purposefully selected from two countries (Kuwait and Jordan). Results: The adapted tool comprised six domains and a total of 14 items. Face and content validity were established through prolonged content analysis. Criterion validity was indicated by significant differences between the healthy and the cerebrovascular accident group in all areas of the Satisfaction Daily Occupations scale (p<0.001). Satisfactory overall internal consistency (=0.77) and good test-retest reliability for the total satisfaction score for the healthy (inter-class correlation coefficient (ICC)=0.984) and the cerebrovascular accident group (inter-class correlation coefficient (ICC)=0.933) were found. Conclusions: The Satisfaction with Daily Occupations-Arabic version is a valid and reliable tool for use with Arabic-speaking occupational therapy clients. This study has several implications for occupational therapy education, practice, and research in the Arab world

Efficacy of metformin monotherapy in newly diagnosed type 2 diabetes mellitus patients treated at Prince Mohammed Bin Abdulaziz hospital, Riyadh, Saudi Arabia

Background: Metformin monotherapy is the primary therapeutic approach in most cases of newly diagnosed type 2 diabetes mellitus (T2DM) as it is safe, efficient, and is known to lower risks like vascular complications in patients. Previous studies have shown that glycemic control provided by metformin monotherapy is not consistent and needs to be monitored in association with other factors. Due to the complex nature of the disease and other factors like genetic predisposition, ethnicity, and geographic distribution, it is crucial to investigate its effect on the Saudi population. This study aimed to evaluate the glycemic response of metformin monotherapy in individuals with newly diagnosed T2DM who had not previously taken any other medications. Methods: A retrospective study model was followed to determine metformin monotherapy in newly diagnosed type 2 diabetes patients. The efficacy of the metformin monotherapy was evaluated in the patients who were drug naive and had undergone treatment for six months. Results: HbA1c levels for our study population (n=136) before and after metformin monotherapy for a period of six months was collected from patient records. The study cohort included both male (n=71) and female (n=67) patients. There was a significant difference in the HbA1c levels of all diabetes patients before (Mean=9.1, SD=2.84) and after (Mean=7.13, SD=1.51) medication; 2-tailed significance p&lt;0.001. Conclusions: Metformin monotherapy was effective in reducing the HbA1c levels across both genders and all age groups in the present study. These results suggest that metformin monotherapy could be the first line of therapy for newly diagnosed T2DM individuals

Oxidative Stress and Ion Channels in Neurodegenerative Diseases

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly investigated for their functional responses to oxidizing agents and oxidative stress. This review primarily explores the relationship and potential links between oxidative stress and ion channels in neurodegenerative conditions, such as cerebellar ataxias and Parkinson’s disease. The potential correlation between oxidative stress and ion channels could hold promise for developing innovative therapies for common neurodegenerative diseases

Dietary Patterns of Females with Cholecystolithiasis: A Comprehensive Study from Central Region of Saudi Arabia

BACKGROUND: Cholecystolithiasis is a worldwide gastrointestinal disorder and dietary pattern is one of the major risk factors involved in formation of cholelithiasis. AIM: This study was undertaken to determine the dietary patterns of female patients with cholecystolithiasis in the central region of Saudi Arabia. METHODS: A total of 332 females respondents were included, among them 157 were cholecystolithiasis cases, whereas 175 were healthy female subjects. All respondents were from central region of Saudi Arabia. Data were collected from a self-administered questionnaire and dietary patterns of studied population samples were compared by Chi-square test using SPSS software. RESULTS: The data showed that the consumption of meat from beef, lamb or goat, butter, ghee, pizza, cereals, legumes, coffee, tea, kabsa rice, tomatoes, and eggs was found to be positively associated with the risk of cholelithiasis. Interestingly, the data also demonstrated that consumption of cakes, chocolates, cookies, ice cream, doughnuts, chicken, fish or other sea foods, French fries, and hot dogs showed no relation with the risk of cholelithiasis. CONCLUSIONS: This study provides a comprehensive description of the dietary patterns of females from central region of Saudi Arabia and their association with the risk of onset of cholelithiasis. Specifically, the majority of non-vegetarian food stuffs showed positive association with the risk of development of cholelithiasis. These findings strongly recommended that the Health Ministry of Saudi Arabia should initiate the specific intervention public health programs on the dietary pattern in relation with the risk of cholelithiasis

Free sugar intake is associated with reduced proportion of circulating invariant natural killer T cells among women experiencing overweight and obesity

BackgroundHigher prevalence of obesity has been observed among women compared to men, which can be explained partly by the higher consumption of sweets and physical inactivity. Obesity can alter immune cell infiltration, and therefore increase the susceptibility to develop chronic inflammation and metabolic disorders. In this study, we aimed to explore the association between free sugar intake and other unhealthy lifestyle habits in relation to the proportion of circulating iNKT cells among women with healthy weight and women experiencing overweight and obesity.MethodsA cross-sectional study was conducted on 51 Saudi women &gt; 18 years, wherein their daily free sugar intake was assessed using the validated Food Frequency Questionnaire. Data on smoking status, physical activity, and supplement use were also collected. Anthropometric data including height, weight, waist circumference were objectively measured from each participants. The proportion of circulating iNKT cells was determined using flow cytometry.ResultsSmoking, physical activity, supplement use, and weight status were not associated with proportion of circulating iNKT cells. Significant association was found between proportion of circulating iNKT cells and total free sugar intake and free sugar intake coming from solid food sources only among women experiencing overweight and obesity (Beta: -0.10: Standard Error: 0.04 [95% Confidence Interval: -0.18 to -0.01], p= 0.034) and (Beta: -0.15: Standard Error: 0.05 [95% Confidence Interval: -0.25 to -0.05], p= 0.005), respectively.ConclusionExcessive free sugar consumption may alter iNKT cells and consequently increase the risk for chronic inflammation and metabolic disorders

Caffeine consumption, intoxication, and stress among female university students: a cross-sectional study

Abstract Background University students use caffeine to cope with stress in spite of its adverse effects. The purpose of this study is to explore caffeine consumption among university students in Saudi Arabia, as well as its correlation with stress and caffeine intoxication. This cross-sectional study examined a convenience sample of 547 students at Princess Nourah Bint Abdulrahman University (PNU). A self-administrated questionnaire was used to assess caffeine consumption in milligrams per day, stress was assessed by the perceived stress scale (PSS), and caffeine intoxication was assessed using the DSM-5 criteria. Results The mean total caffeine consumption was 424.69 ± 385.31 mg/day. High levels of caffeine consumption were found among students of non-health colleges and students who were undiagnosed with psychiatric disorders (p values <0.040 and 0.027, respectively). A significant positive correlation was found between caffeine consumption and perceived stress (p<0.045). Only 13.26% of all participants fulfilled the DSM-5 criteria for caffeine use disorder. The majority of participants showed moderate and high stress levels (69.9% and 18.7%). Conclusion This study revealed high caffeine consumption and perceived stress levels among female undergraduate students with a significant positive association between them. The results emphasize the importance of educational campaigns about caffeine consumption and intoxication. They also encourage the development of stress management programs. Longitudinal studies need to be designed for evidence-based intervention

A case series of actinomycosis from a single tertiary care center in Saudi Arabia

Actinomycosis is an uncommon but curable chronic infection caused by Actinomyces spp. The cervicofacial region is the most susceptible to infection; however, other sites may also become infected. Data on the current prevalence of this rare disease in Riyadh, Saudi Arabia is lacking. We herein report a case series of four patients with actinomycosis from a single tertiary care center in Riyadh, Saudi Arabia.Three patients presented to us with slowly progressing actinomycosis and one patient developed an acute abdomen, secondary to viscus perforation. Two of the patients had cervicofacial disease, including hard palate actinomycosis. Tissue cultures were sent for three patients; however, tests for actinomycosis were negative. Subsequently, the diagnosis was made through histopathological examination. Therapy involved a combination of surgical resection and debridement and prolonged antimicrobial treatment tailored to each patient.The cases reported in this series highlight the difficulty in diagnosing actinomycosis. For most patients, the diagnosis was delayed or accidentally discovered on histopathological examination. We conclude that increased awareness among physicians is needed for early diagnosis and treatment of actinomycosis

Rapid cycle training for non-critical care physicians to meet intensive care unit staff shortage at an academic training center in a developing country during the COVID-19 pandemic

Abstract Background The sudden unexpected increase in critically ill COVID-19 patients admitted to Intensive Care Units (ICUs), resulted in an urgent need for expanding the physician workforce. A COVID-19 critical care crash (5C) course was implemented to introduce physicians without formal critical care training to care for critically ill COVID-19 patients. Upon successful completion of the course, physicians were recruited to work in a COVID-19 ICU under the supervision of a board-certified critical care physician. The aim of this study is to describe the methods of a novel course designed specifically to teach the management critically ill COVID-19 patients, while assessing change in knowledge, skill competency, and self-reported confidence. Methods The blended focused 5C course is composed of both virtual and practical components. Candidates may register for the practical component only after successful completion of the virtual component. We assessed knowledge acquisition using a multiple-choice question test (pre- and post-test assessment), skill competency, and self-reported confidence levels during simulated patient settings. Paired T-test was used to compare before and after course results. Results Sixty-five physicians/trainees from different specialties were included in the analysis. Knowledge significantly increased from 14.92± 3.20 (out of 20 multiple-choice questions) to 18.81± 1.40 (p< 0.01), skill competence during practical stations had a mean minimum of 2 (out of 3), and self-reported confidence during a simulated patient setting increased significantly from 4.98± 1.15 (out of 10) to 8.76± 1.10 (out of 10) (p< 0.01). Conclusion We describe our initiative in increasing the ICU physician workforce in the midst of the COVID-19 pandemic. The blended 5C course is a valuable educational program designed by experts from different backgrounds. Future research should be directed at examining outcomes of patients associated with graduates of such program

Chromatographic and spectroscopic methods for the detection of cocoa butter in cocoa and its derivatives: A review

Currently, there is fierce competition in the cocoa industry to develop products that possess distinctive sensory characteristics and flavours. This is because cocoa and its derivatives provide numerous health and functional advantages, which is essential to their economics. The fatty acid and triglyceride composition of cocoa determines its quality. This review emphasises the necessity of developing precise, adaptable analytical techniques to identify and quantify cocoa butter in cocoa and its derived products, from cocoa beans to chocolate bars. Key chromatographic and spectroscopic techniques play crucial roles in understanding the fundamental principles underlying the production of cocoa with desirable flavours. This significantly impacts the sustainability, traceability, and authenticity of cocoa products while also supporting the battle against adulteration