The potential role of brain renin-angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?

Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin-angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well-known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non-classical pathway which is mostly mediated by ACE2/Ang1-7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD.

Smartphone use and its association with body image distortion and weight loss behaviours among adolescents in Saudi Arabia.

BACKGROUND: Concerns about the harmful effects of smartphone use on teenage development have been raised as the use of cell phones among adolescents has risen. OBJECTIVE: This study aimed to examine the associations of smartphone usage patterns with Body Image Distortion (BID) and weight loss behaviors among adolescent smartphone users in Saudi Arabia. METHODS: This population-based, cross-sectional study was conducted from July to October 2022. We assessed the mean daily length of smartphone use and classified it into quartiles using data from a self-reported survey and data on weekday and weekend use. Self-reported body weight and height were collected via an online survey. Out of the 11384 adolescents, the majority was females (65.7%) and was secondary school students (68.9%). RESULTS: The prolonged smartphone use (301 min/d) was found in 36.4% of adolescents, 181-300 min/d in 27.6% of respondents, 121-180 min/d in 22.4% of respondents, while the modest smartphone use (1-120 min/d) was found only in 13.6% of participants. The duration of smartphone use was significantly associated with BID (P= 0.000); students with middle perceived stress levels (51.4%) and no depressive symptoms (68.9%) used smartphones 121-180 min/d sparingly. However, prolonged smartphone use was significantly associated with the presence of depressive symptoms (42.6%) and high perceived stress levels (21.5%). Weight loss behaviors were significantly associated with smartphone use duration. Modest smartphone use was significantly found in students with normal weight (P= 0.00, 71.9%); however, aerobic physical activity weight loss strategy (P= 0.00, 30.9%) was correlated with prolonged smartphone use. CONCLUSION: Adequate parental advice is required to assist teenagers in developing healthy smartphone usage practices. Digital platform companies may increase their social responsibility for the information generated and delivered on their networks, boosting its beneficial effect.

Study to Determine the Prevalence of Menstrual Migraine in Reproductive-Age Women in Saudi Arabia.

BACKGROUND: Migraine is a common health condition in both men and women. Premenstrual syndrome (PMS) affects many women during their menstrual cycle, with around 50-60% of women with migraine attacks experiencing menstrual headaches. Most have mild symptoms, but 5-8% suffer from moderate to severe symptoms, causing distress and functional issues. Pure menstrual migraine (PMM) occurs in about 50% of women with migraine, and it can be debilitating in terms of frequency and severity. This information is crucial for Saudi Arabian medical professionals to provide better care and support, improving the quality of life for women with PMS and menstrual migraine (MM) attacks. OBJECTIVES: To estimate the prevalence of MM in women, to evaluate the severity and frequency of MM in women with PMS, and to identify potential risk factors aggravating MM in women with PMS in Saudi Arabia. METHODOLOGY: A cross-sectional community-based study was conducted on reproductive-aged (18-50 years) women who had regular menstrual cycles and were diagnosed with PMS, using a self-administered questionnaire between December 2022 to May 2023 in Saudi Arabia. RESULTS: Out of the 2130 female participants, 397 (18.6%) had migraine. Among these 397 migraine sufferers, 230 (57.9%) experienced MM, while 167 (42.1%) had non-MM. In reproductive women in general, MM occurred in 10.7% of cases, while non-MM was observed in 7.8%. There is a correlation between increasing BMI and an increased incidence of MM. About one-third of the participants experienced moderate disability due to migraine attacks, with 134 (33.8%) individuals affected. Additionally, most MM sufferers missed at least 3 days of work in the last 3 months due to their condition. CONCLUSIONS: Migraine attacks occurring during the menstrual cycle impair the ability to engage in social, physical, household, and academic activities, often hindering the fulfillment of professional commitments. To gain a deeper understanding of menstrual and non-menstrual migraine attacks, it is essential to conduct extensive prospective studies aimed at developing effective management strategies.

Memory, Attention, and Concentration Dysfunction Post-COVID-19 Among College Students in Saudi Arabia: A Case-Control Study.

Introduction Multiple studies have demonstrated the multi-systemic involvement of COVID-19, and among all of these systems, there is mounting evidence that COVID-19 is linked to neurocognitive impairment, particularly when neurological symptoms are present. Our aim is to study the concept of cognitive dysfunction post-COVID-19 among college students in Saudi Arabia and its potential effect on their academic performance.  Methods A population-based, observational case-control study was conducted across the Kingdom of Saudi Arabia, from May 2022 to September 2022. A total of 2,150 eligible students have completed the study questionnaire. An exact 776 (36.1%) of them had COVID-19 infection (group 1), while 1,374 (63.9%) students had not (group 2). The sample population was college-enrolled students from 18 to 28 years old, with a mean age of 21.3 for group 1 and 20.8 for group 2. Both groups were handed the same data collection tool to establish whether the COVID-19 survivors had cognitive deficits more than the control group. Results There was no significant difference between the two groups regarding their bio-demographic data, study methods, or vaccination rate. However, both Neurological Fatigue and Big Five Inventory score were significantly higher among infected students, comparable to non-infected students. A negative relation was found between the infected students' neurological fatigue (rho=-0.14), cognitive failure (rho=-0.10), and depression and anxiety scale with their GPA (rho=0.03). Contrarily, infected students showed a positive relationship between their GPA and the Big Five Inventory (rho=0.13) and Short Grit Scale (rho=0.14). Also, there was a significant inverse relation between students' apathy motivation with their Big Five Inventory. Likewise, there was an inverse relation between their neurological fatigue, cognitive failure, and apathy motivation with their Short Grit Scale. Conclusion We demonstrated that college students who have survived COVID-19 infection mostly complain of cognitive impairment, even though most of them have no comorbidities or psychological disorders.

Suppression of neuronal apoptosis and glial activation with modulation of Nrf2/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy.

Introduction: Diabetes is a global disease, commonly complicated by neuropathy. The spinal cord reacts to diabetes by neuronal apoptosis, microglial activation, and astrocytosis, with a disturbance in neuronal and glial Nuclear factor erythroid 2-related factor/Heme oxygenase-1 (Nrf2/HO-1) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling. Curcumin, a bioactive natural substance, showed neuroprotective role in many diseases. However, its role in the treatment of the diabetic central neuropathy of spinal cord and the underlying mechanisms still need clarification. The present study tried to evaluate the role of curcumin in diabetes-induced central neuropathy of the spinal cord in rats. Methods: Twenty rats were divided into three groups; group 1: a negative control group; group 2: received streptozotocin (STZ) to induce type I diabetes, and group 3: received STZ + Curcumin (150 mg/kg/day) for eight weeks. The spinal cords were examined for histopathological changes, and immunohistochemical staining for Glia fibrillary acidic protein (GFAP); an astrocyte marker, Ionized calcium-binding adaptor molecule 1 (Iba1), a microglial marker, neuronal nuclear protein (NeuN); a neuronal marker, caspase-3; an apoptosis marker, Nrf2/HO-1, NF-kB, and oxidative stress markers were assessed. Results: Curcumin could improve spinal cord changes, suppress the expression of Iba1, GFAP, caspase-3, and NF-kB, and could increase the expression of NeuN and restore the Nrf2/HO-1 signaling. Discussion: Curcumin could suppress diabetic spinal cord central neuropathy, glial activation, and neuronal apoptosis with the regulation of Nrf2/HO-1 and NF-kB signaling.

Online Health Information Seeking by Individuals With Physical Disabilities Caused by Neurological Conditions in Saudi Arabia.

Background In recent years, there has been an increase in the use of the internet and information technology for accessing health information. This study aimed to determine the factors that affect patients with neurological disabilities and their willingness to search for information via the internet. In addition, we aimed to assess how patients manage this information, considering the increasing availability of online information and websites that discuss health and diseases, as well as the spread of communication technology and its accessibility to the public. Methodology A cross-sectional, online, self-administered, questionnaire study was conducted in Saudi Arabia. The study targeted patients with neurological diseases who had disabilities. The questionnaire was designed to measure the demographic data, physical disability using the 10-item physical function component of the 36-Item Short Form Health survey, the perceived usefulness of online health information, the perceived ease of use, and the perceived risk of online health information. Lastly, the questionnaire measured online health information-seeking intentions and information use. Data analysis was performed using RStudio (R version 4.1.1, Posit, Boston, USA). Results We received 1,179 responses, of which 399 were excluded due to using another way to get information rather than the internet, 31 did not have neurological disabilities, and 136 did not complete the questionnaire. The remaining 613 responses were included in the final analysis. The participants were mostly male (54.6%), not married (54.6%), and had a bachelor's degree (49.99%). The average age of participants was 18-25 years (24.5%) and 26-35 years (23.2%), Additionally, most participants resided in the western (26.9%) and eastern (25.9%) regions. Most participants (39.5%) had a monthly income of 5,000 to 10,000 SAR. Further, the most common neurological diseases were multiple sclerosis and epilepsy (26.9% and 23.2%, respectively). Based on the analysis of the data, the most important factor affecting online health information-seeking intention was that people with higher monthly incomes were more likely to seek online health information; these included people with an income of 10,000-20,000 SAR and >20,000 SAR. The most common factor affecting information use was the region of residence. The southern and western regions were less likely to adopt information use. Conclusions The monthly income and the area of residence had the greatest impact on people with neurological disabilities who sought online health information in the Kingdom of Saudi Arabia. Educational campaigns and workshops should be arranged to increase the population's awareness of this topic, as well as to reveal the extent and prevalence of online health information seeking among disabled patients.

Expanding the genotype-phenotype landscape of PDE10A-associated movement disorders.

BACKGROUND: Phosphodiesterase 10A (PDE10A) controls body movements by regulating cyclic adenosine monophosphate signaling in the basal ganglia. Two classes of PDE10A variants are reported with distinctive genotype-phenotype correlation. The autosomal recessive mutations in the GAF-A and catalytic domains are associated with compromised membrane localization, and manifest with infantile onset chorea, developmental, and cognition delay with normal brain MRI. Conversely, autosomal dominant mutations in the GAF-B domain cause protein aggregates which results in childhood onset chorea in the context of normal cognition and development, with striatal lesions. METHODS: Phenotypic characteristics of affected individuals with PDE10A mutations belonging to a single family were recorded. In addition, Sanger sequencing and in silico analysis were used to identify the mutations. Homozygosity mapping was applied together with whole exome sequencing. RESULTS: Four individuals from a consanguineous family affected with PDE10A mutations were observed for up to 40 years. Although these individuals displayed a clinical phenotype attributed to the recessive GAF-A mutations, they revealed a bi-allelic GAF-B mutation (c.883G > A:p. D295 N; p.Asp295Asn) that was segregated with all affected individuals. In addition to chorea, we observed peculiar foot deformities and pronounced social phobia, with normal brain MRI. In silico structural analysis suggested that the GAF-B mutation blocked allosteric PDE10A activation. The resulting lack of PDE10A activity likely phenocopies GAF-A mutations, and this is achieved through a distinct mechanism. CONCLUSIONS: Collectively, our findings demonstrate the association of recessive and dominant phenotypes of known variants, and further expands the genotype-phenotype landscape of PDE10A-associated movement disorders.

Awareness of Stroke Risk Factors and Warning Signs Among Diabetic Patients in the Aseer Region, Saudi Arabia: A Cross-Sectional Study.

Objective This study aimed to determine the awareness of stroke risk factors and warning signs among diabetic patients in the Aseer Region, Saudi Arabia. Methods We adopted a cross-sectional study involving 314 participants in the Aseer Region, Saudi Arabia between February 27, 2023, and April 20, 2023. The target population was diabetic patients whose database was obtained from various health institutions. The questionnaire was then distributed to the respondents after obtaining informed consent. The data were analyzed using SPSS Statistics version 27.0.1.0 (IBM Corp., Armonk, NY, USA) to obtain important insights. Results The majority of the respondents (69.11%) demonstrated a good level of knowledge, while 30.89% had poor knowledge. A good proportion of the respondents (68.47%) knew about stroke, while 73.89% knew it primarily affects the brain. Most respondents claimed that elderly people were at higher risk of attack (52.55%) and that the younger population was also prone to stroke (64.97%). The respondents identified hypertension (74.52%), smoking (72.61%), diabetes (71.66%), and high blood cholesterol (68.47%) as the main risk factors for stroke. The participants also demonstrated a very good understanding of the warning signs, with difficulty speaking (80.57%) and the weakness or inability to move one-half of the body (85.35%) being the most common signs. Conclusion The findings in this study indicated a good level of understanding and awareness of stroke, its risk factors, and warning signs (69.11%). The older respondents and people with a higher level of education demonstrated more knowledge. The two variables, age and education, had a statistically significant relationship with the knowledge of stroke. The common risk factors associated with stroke were identified as hypertension, smoking, diabetes, and high blood cholesterol. The respondents demonstrated good knowledge of the warning signs, with the vast majority asserting that difficulty in speaking, decreased sensation, and weakness or inability to move one-half of the body are common warning signs.

Evaluation of the Cytological Changes of the Oral Mucosa Among Smokers in Al Madinah Al Munawara Using Argyrophilic Nucleolar Organizer Region (AgNOR) Counts and Papanicolaus Stain.

Objective To evaluate the cytological changes of the oral mucosa among smokers using Argyrophilic nucleolar organizer region (AgNOR) counts and Papanicolaou (Pap) staining. Methodology The oral mucosal exfoliate smears of 500 individuals (200 nonsmokers and 300 smokers) aged between 18 and 80 years were prepared in Al Madinah. The AgNOR count and Pap stain were used to generate a cytogenic smear to assess the presence of cytological changes suggestive of atypia, inflammation, dysplasia, keratinization, and proliferative activity of epithelial cells. Results Smokers have a considerably higher number of AgNORs per nucleus than nonsmokers (1.99 3.53 vs. 0.42 1.22). There were inflammatory changes in 127 (42.3%) of the cases and 40 (20%) of the controls. Multinucleated cells and atypia were found in 33 (11%) and 14 (4.5%) of the cases but not in the controls. The results indicate higher proliferative activity in smoking patients compared to nonsmoking patients, even in the absence of clinical lesions. Conclusion To detect the effects of smoking on the oral mucosa, Pap staining alone is insufficient. Combining Pap staining with the AgNOR technique produces the desired results.

Neuroprotective effect of naringin against cerebellar changes in Alzheimer's disease through modulation of autophagy, oxidative stress and tau expression: An experimental study.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual cognitive decline. Strong antioxidants that inhibit free radicals, such as polyphenols, reduce the likelihood of developing oxidative stress-related degenerative diseases such as AD. Naringin, a flavonoid found in citrus fruit shown to be neuroprotective, reduce oxidative damage and minimize histopathological changes caused by ischemic reperfusion, enhance the long-term memory in AD animal models. This work aimed to comprehend the role of naringin in the defense of the cerebellum against aluminum chloride (AlCl3)-induced AD in rats by investigating the behavioral, neurochemical, immunohistochemical, and molecular mechanisms that underpin its possible neuroprotective effects. Twenty-four adult albino rats were divided into four groups (n = 6/group): (i) Control (C) received saline per oral (p.o.), (ii) Naringin(N)-received naringin (100 mg/kg/d) p.o, (iii) AlCl3-recived AlCl3 (100 mg/kg/d) p.o and (iv) AlCl3 + Naringin (AlCl3 + N) received both AlCl3 and naringin p.o for 21 days. Behavioral tests showed an increase in the time to reach the platform in Morris water maze, indicating memory impairment in the AlCl3-treated group, but co-administration of naringin showed significant improvement. The Rotarod test demonstrated a decrease in muscle coordination in the AlCl3-treated group, while it was improved in the AlCl3 + N group. Neurochemical analysis of the hippocampus and cerebellum revealed that AlCl3 significantly increased lipid peroxidation and oxidative stress and decreased levels of reduced glutathione. Administration of naringin ameliorated these neurochemical changes via its antioxidant properties. Cerebellar immunohistochemical expression for microtubule assembly (tau protein) and oxidative stress (iNOS) increased in A1C13-treated group. On the other hand, the expression of the autophagic marker (LC3) in the cerebellum showed a marked decline in AlCl3-treated group. Western blot analysis confirmed the cerebellar immunohistochemical findings. Collectively, these findings suggested that naringin could contribute to the combat of oxidative and autophagic stress in the cerebellum of AlCl3-induced AD.