Associations of Electronic Device Use and Physical Activity with Headaches in Saudi Medical Students.

Background and Objectives: Primary headaches are highly prevalent among medical students, negatively impacting their health and academic performance. Excessive electronic device use has been implicated as a risk factor, in contrast to physical activity, which may be a protective factor; however, comprehensive data are lacking, especially for Saudi medical trainees. This study aims to investigate the associations between device use, exercise, and headaches among Saudi medical students. Materials and Methods: In this cross-sectional study, 504 medical students at Jazan University completed an online survey collecting sociodemographic factors, headache characteristics/triggers, electronic device habits, exercise frequency, and headache impacts. Descriptive analyses summarized sample characteristics. Logistic regression identified predictors of 12-month headache prevalence. Results: Overall, 83% reported experiencing headaches in the past year. High headache prevalence was observed among females (86.6%) and third-year students (88.3%). Using electronic devices ≥4 h daily was associated with higher adjusted odds of headaches (OR 13.89, 95% CI 1.96-98.54) compared to ≤1 h daily. Low physical activity (exercising 1 day vs. 7 days a week) also increased headache odds (OR 3.89, 95% CI 1.61-9.42). Headaches impairing productivity (OR 4.39, 95% CI 2.28-8.45) and exacerbated by exercise (OR 10.37, 95% CI 2.02-53.35) were further associated with headache susceptibility. Conclusions: Excessive electronic device use and physical inactivity appear to be modifiable risk factors for frequent headaches in Saudi medical students. Multifaceted interventions incorporating education campaigns, skills training, and support services focused on promoting responsible technology habits, and regular exercise may help mitigate headaches in this population. Robust longitudinal studies and trials are warranted to establish causal mechanisms between lifestyle factors and headaches among medical undergraduates.

Protein supplement intake by non-athlete gym attendees in Jazan region: misconceptions and gender differences.

BACKGROUND: Protein supplements (PSs) have gained widespread popularity among non-athlete gym attendees, who often perceive them as essential tools for muscle growth and recovery. However, misinformation surrounding PSs may lead to inappropriate use and negative health consequences. This study aimed to assess whether non-athlete gym attendees using PSs have greater misconceptions than non-users while also examining the prevalence of PS consumption and gender differences. METHODS: A cross-sectional study of 387 participants in the Jazan region was conducted. Customers of 10 fitness centers were screened with a questionnaire comprising questions to measure PS misconceptions. Participants were divided into PS users and non-users. Data were analyzed using descriptive statistics and the Chi-square test to assess the associations between variables. An independent t-test was used to compare the PS Misconception Index Score between the two groups. RESULTS: A total of 82.4% of non-athlete gym attendees consumed at least one PS. Our findings revealed a significant association between gender and PS utilization (P<0.001), with a higher proportion of females (90.8%) consuming PS than males (77.6%). PS users had a significantly lower PS Misconception Index Score than non-users (26.8 vs. 28.3; P=0.006), indicating that PS users had a higher number of misconceptions. The internet (41.37%) and coaches (gym instructors/trainers) (34.48%) were the most common sources of information about PSs, with muscle gain being the primary reason for consumption (82.75%). CONCLUSIONS: PS consumption is highly prevalent among non-athlete gym attendees in the Jazan region, with many individuals having misconceptions about their benefits and potential risks. Targeted educational interventions are needed to promote evidence-based knowledge about PSs for gym attendees, as well as for coaches, given that they were among the primary sources of information on supplements.

Nrf2 and autonomic dysregulation in chronic heart failure and hypertension.

Redox imbalance plays essential role in the pathogenesis of cardiovascular diseases. Chronic heart failure (CHF) and hypertension are associated with central oxidative stress, which is partly mediated by the downregulation of antioxidant enzymes in the central autonomic neurons that regulate sympathetic outflow, resulting in sympathoexcitation. Antioxidant proteins are partially regulated by the transcriptional factor nuclear factor erythroid 2-related factor 2 (Nrf2). Downregulation of Nrf2 is key to disrupting central redox homeostasis and mediating sympathetic nerve activity in the setting of Chronic heart failure and hypertension. Nrf2, in turn, is regulated by various mechanisms, such as extracellular vesicle-enriched microRNAs derived from several cell types, including heart and skeletal muscle. In this review, we discuss the role of Nrf2 in regulating oxidative stress in the brain and its impact on sympathoexcitation in Chronic heart failure and hypertension. Importantly, we also discuss interorgan communication via extracellular vesicle pathways that mediate central redox imbalance through Nrf2 signaling.

Physical Activity, Mental Health, and Quality of Life among School Students in the Jazan Region of Saudi Arabia: A Cross-Sectional Survey When Returning to School after the COVID-19 Pandemic.

Increasing evidence suggests that physical activity (PA) can reduce depression and anxiety in adolescents. At the same time, quality of life (QoL) is sensitive to both mental health and PA, but little is known about the mechanism between these three variables among adolescents. This study aimed to assess the physical activity, mental health, and quality of life of school students when they returned to school after two years of distance learning in the Jazan region. This current investigation represented an observational cross-sectional survey conducted in January 2022 among a random sample of 601 students from intermediate and high schools in the Jazan region, Saudi Arabia. Three standardized questionnaires were used for data collection; the Arabic version of the Pediatric Quality of Life Inventory (PedsQL), Depression Anxiety Stress Scales (DASS21), and the Fels PAQ for children. The analysis revealed a moderate level of physical activity, decreased HRQoL, and symptoms of mental health problems (anxiety, depression, and stress) among the schools' students when they returned to school following COVID-19 lockdown. The overall Pediatric Quality of Life mean score was (81.4 ± 16.4), which differed significantly according to gender, age groups, and grade levels (p < 0.05 for all). There was a negative correlation between the overall quality of life and mental health domains. Sport was negatively correlated with mental illness symptoms and positively correlated (p < 0.05) with Pediatric Quality of Life. The regression models revealed that stress was a significant predictor for the quality of life of male and female adolescents ([ß = -0.30, (95% CI (-0.59) to (-0.02), p < 0.05)] and [ß = -0.40, (95% CI (-0.70) to (-0.01), p < 0.05)], respectively). The analysis revealed a moderate level of physical activity among the schools' students when they returned to school following COVID-19 lockdown. Children's involvement in physical activity was associated with improved quality of life and mental health. The results call for the need to develop appropriate intervention programs to increase school students' physical activity levels.

The Impact of COVID-19 on Maintaining Physical Activity and Its Associated Factors among Medical Students.

BACKGROUND: Stay-home orders and the shutdown of university campuses and fitness centers have greatly influenced health behaviors, resulting in a widespread reduction in physical activity. This study aimed to identify factors associated with maintaining physical activity among Jazan University medical students during the COVID-19 shutdown. METHODS: An official Arabic short form of the International Physical Activity Questionnaire was used to assess physical activity before and during the COVID-19 home quarantine. Differences between groups were examined using chi-square analyses and the Mann-Whitney U test. Multinomial logistic regression was used to test whether certain demographic and exercise-related variables were significant predictors of maintaining physical activity levels during the COVID-19 pandemic. RESULTS: More than half of the participants (53%) reported no change or increased physical activity level. Several factors were significantly related to physical activity heterogeneity including income (p = 0.04), fitness center membership (p < 0.01), usage of fitness tracker devices (p < 0.01), and the purchase of physical activity equipment during the COVID-19 pandemic (p < 0.01). The odds of maintaining physical activity were higher among those who tracked their physical activity (AOR = 6.160; 95% CI = 3.782-10.032, p < 0.001). Similarly, the odds of maintaining physical activity were higher among those who purchased home-exercise equipment during the pandemic (AOR = 2.243; 95% CI = 1.386-3.632, p = 0.001). CONCLUSIONS: Understanding the factors affecting physical activity behaviors is an essential step toward addressing the reduction in physical activity. This could help maintain physical activity levels during a potential future pandemic-related shutdown.

Burnout Among School Teachers During the COVID-19 Pandemic in Jazan Region, Saudi Arabia.

Background: Burnout is a syndrome that results from stressors in the work environment that have not been successfully managed. The prevalence of burnout among schoolteachers was always controversial. COVID-19 pandemic added more stressors to teachers since they had to change their working styles in response to the pandemic lockdowns or curfews. In Saudi Arabia, the prevalence and determinants of burnout among school teachers were not measured by any other group during the COVID-19 pandemic stressors. Methods: A cross-sectional survey was conducted among 879 teachers in the Jazan region, Saudi Arabia, using the Maslach Burnout Inventory (MBI), during April 2021. Multistage cluster random sampling was used. Results: The mean age of the participants was 41.4 (±6.9) years. Male teachers represented 52.6% of the participants while females represented 47.4%. Most teachers showed burnout symptoms (69.6%). Consequences of burnout were observed, such as using psychotropic medications (4.6%), absenteeism (45.6%), lack of job satisfaction (7.7%), and changing schools (15.8%). Using the MBI scale, most teachers showed medium or high emotional exhaustion (57.6%), low depersonalization (62.2%), and low personal accomplishment (51.4%). Conclusion: Most teachers showed symptoms of burnout during the COVID-19 pandemic. Being an expert and ability to adapt to technology during the COVID-19 pandemic proved to effectively reduce burnout symptoms. Increasing incentives, early detection, and improving the work environment is recommended to diminish burnout consequences.

Functional, proteomic and bioinformatic analyses of Nrf2- and Keap1- null skeletal muscle.

KEY POINTS: Nrf2 is a master regulator of endogenous cellular defences, governing the expression of more than 200 cytoprotective proteins, including a panel of antioxidant enzymes. Nrf2 plays an important role in redox haemostasis of skeletal muscle in response to the increased generation of reactive oxygen species during contraction. Employing skeletal muscle-specific transgenic mouse models with unbiased-omic approaches, we uncovered new target proteins, downstream pathways and molecular networks of Nrf2 in skeletal muscle following Nrf2 or Keap1 deletion. Based on the findings, we proposed a two-way model to understand Nrf2 function: a tonic effect through a Keap1-independent mechanism under basal conditions and an induced effect through a Keap1-dependent mechanism in response to oxidative and other stresses. ABSTRACT: Although Nrf2 has been recognized as a master regulator of cytoprotection, its functional significance remains to be completely defined. We hypothesized that proteomic/bioinformatic analyses from Nrf2-deficient or overexpressed skeletal muscle tissues will provide a broader spectrum of Nrf2 targets and downstream pathways than are currently known. To this end, we created two transgenic mouse models; the iMS-Nrf2flox/flox and iMS-Keap1flox/flox , employing which we demonstrated that selective deletion of skeletal muscle Nrf2 or Keap1 separately impaired or improved skeletal muscle function. Mass spectrometry revealed that Nrf2-KO changed expression of 114 proteins while Keap1-KO changed expression of 117 proteins with 10 proteins in common between the groups. Gene ontology analysis suggested that Nrf2 KO-changed proteins are involved in metabolism of oxidoreduction coenzymes, purine ribonucleoside triphosphate, ATP and propanoate, which are considered as the basal function of Nrf2, while Keap1 KO-changed proteins are involved in cellular detoxification, NADP metabolism, glutathione metabolism and the electron transport chain, which belong to the induced effect of Nrf2. Canonical pathway analysis suggested that Keap1-KO activated four pathways, whereas Nrf2-KO did not. Ingenuity pathway analysis further revealed that Nrf2-KO and Keap1-KO impacted different signal proteins and functions. Finally, we validated the proteomic and bioinformatics data by analysing glutathione metabolism and mitochondrial function. In conclusion, we found that Nrf2-targeted proteins are assigned to two groups: one mediates the tonic effects evoked by a low level of Nrf2 at basal condition; the other is responsible for the inducible effects evoked by a surge of Nrf2 that is dependent on a Keap1 mechanism.

Overexpression of Central ACE2 (Angiotensin-Converting Enzyme 2) Attenuates the Pressor Response to Chronic Central Infusion of Ang II (Angiotensin II): A Potential Role for Nrf2 (Nuclear Factor [Erythroid-Derived 2]-Like 2).

We investigated the mechanism by which ACE2 (angiotensin-converting enzyme 2) overexpression alters neurohumoral outflow and central oxidative stress. Nrf2 (nuclear factor [erythroid-derived 2]-like 2) is a master antioxidant transcription factor that regulates cytoprotective and antioxidant genes. We hypothesized that upregulation of central ACE2 inhibits the pressor response to Ang II (angiotensin II) by reducing reactive oxygen species through a Nrf2/antioxidant enzyme-mediated mechanism in the rostral ventrolateral medulla. Synapsin human Angiotensin Converting Enzyme 2 positive (SynhACE2+/+) mice and their littermate controls synhACE2-/- were used to evaluate the consequence of intracerebroventricular infusion of Ang II. In control mice, Ang II infusion evoked a significant increase in blood pressure and norepinephrine excretion, along with polydipsia and polyuria. The pressor effect of central Ang II was completely blocked in synhACE2+/+ mice. Polydipsia, norepinephrine excretion, and markers of oxidative stress in response to central Ang II were also reduced in synhACE2+/+ mice. The MasR (Mas receptor) agonist Ang 1-7 and blocker A779 had no effects on blood pressure. synhACE2+/+ mice showed enhanced expression of Nrf2 in the rostral ventrolateral medulla which was blunted following Ang II infusion. Ang II evoked nuclear translocation of Nrf2 in cultured Neuro 2A (N2A) cells. In synhACE2-/- mice, the central Ang II pressor response was attenuated by simultaneous intracerebroventricular infusion of the Nrf2 activator sulforaphane; blood pressure was enhanced by knockdown of Nrf2 in the rostral ventrolateral medulla in Nrf2 floxed (Nrf2f/f) mice. These data suggest that the hypertensive effects of intracerebroventricular Ang II are attenuated by selective overexpression of brain synhACE2 and may be mediated by Nrf2-upregulated antioxidant enzymes in the rostral ventrolateral medulla.

Exercise training upregulates Nrf2 protein in the rostral ventrolateral medulla of mice with heart failure.

Chronic heart failure (CHF) is associated with global oxidative stress, which contributes to sympathoexcitation. Increased reactive oxygen species in the brain accumulate within neurons and lead to enhanced neuronal excitability. Exercise training (ExT) is associated with a reduction of oxidative stress by upregulation of antioxidant enzymes. The link between ExT and antioxidant enzyme expression in the brain of animals with CHF is not clear. We hypothesized that ExT enhances transcription and translation of the nuclear factor erythroid 2-related factor 2 (Nrf2) gene, a master transcription factor that modulates antioxidant enzyme gene expression, in the rostral ventrolateral medulla (RVLM) of mice with CHF. Mice were divided into the following groups: Sham sedentary (Sham-Sed), Sham-ExT, CHF-Sed, and CHF-ExT. After 8 wk of ExT, we measured Nrf2 and NAD(P)H dehydrogenase [quinone] 1 (NQO-1) message and protein expression along with maximal exercise tolerance and urinary norepinephrine (NE) excretion. We found that Nrf2 and NQO-1 mRNA and protein expression in the RVLM were lower in CHF-Sed mice compared with Sham-Sed. ExT attenuated the CHF-induced reduction of Nrf2 and NQO-1 mRNA and protein expression in the RVLM. NE excretion was higher in CHF-Sed mice compared with Sham-Sed (666.8 ± 79.3 ng/24 h, n = 6 vs. 397.8 ± 43.7 ng/24 h, P = 0.04). CHF-ExT mice exhibited reduced urinary NE excretion compared with CHF-Sed (360.7 ± 41.7 ng, n = 4 vs. 666.8 ± 79.3 ng, n = 6; P = 0.03). We conclude that ExT-induced upregulation of Nrf2 in the RVLM contributes to the beneficial effects of ExT on sympathetic function in the heart failure state.NEW & NOTEWORTHY This study provide evidence for an important role for exercise training in the modulation of antioxidant enzyme production in the rostral ventrolateral medulla (RVLM) in the heart failure state. We show here a correlation between exercise training and the expression of the antioxidant transcription factor Nrf2 in the RVLM. Exercise training reduced sympathetic function (norepinephrine excretion) and upregulated both Nrf2 and the antioxidant enzyme NQO-1. We conclude that Nrf2 in the RVLM may be an important target for controlling sympathetic outflow in heart failure.

Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle.

A hallmark of chronic heart failure (HF) with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin, a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Curcumin was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg·kg-1·day-1 for 8 weeks. In vivo, in situ, and in vitro experiments were employed to evaluate exercise capacity, muscle function, and molecular mechanisms. We found that: 1) the maximal speed, running distance to exhaustion, and limb grip force were significantly lower in HFrEF mice compared with sham. Curcumin-treated HF mice displayed enhanced exercise performance compared with vehicle-treated HF mice; 2) both soleus (Sol) and extensor digitorum longus (EDL) muscles of HFrEF mice exhibited reduced force and rapid fatigue, which were ameliorated by curcumin; and 3) protein expression of Nrf2, hemeoxygenase-1, SOD2, myogenin, and MyoD were significantly lower, but total ubiquitinated proteins, MURF1, and atrogen-1 were higher in Sol and EDL of HFrEF compared with sham mice, whereas these alterations in Nrf2 signaling and antioxidant defenses in HFrEF were attenuated by curcumin, which had no effect on cardiac function per se in mice with severe HFrEF. These data suggest that impaired Nrf2 signaling intrinsic to skeletal muscle contributes to exercise intolerance in HFrEF. Skeletal muscle Nrf2 should be considered as a novel therapeutic target in severe HF. NEW & NOTEWORTHY These studies suggest that impaired nuclear factor E2-related factor 2 (Nrf2) signaling is a critical mechanism underlying the enhanced oxidative stress in skeletal muscle in heart failure with low ejection fraction (HFrEF). Curcumin prevents the decline in running performance in HFrEF mice by upregulating antioxidant defenses in skeletal muscle, likely mediated by activating Nrf2 signaling. These findings suggest a novel therapeutic target for the improvement of exercise capacity and quality of life in HFrEF patients.