ALSUntangled #75: Portable neuromodulation stimulator therapy.

Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.

ALSUntangled #74: Withania Somnifera (Ashwagandha).

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progression because of its effects on inflammation, oxidative stress, autophagy, mitochondrial function, and apoptosis. Preclinical trials demonstrate that WS slows disease progression in multiple different animal models of ALS. Of the five individuals we found who described using WS for their ALS, two individuals reported moderate benefit while none reported experiencing any significant side effects. There is currently one clinical trial using WS to treat PALS; the results are not yet published. There are no serious side effects associated with WS and the associated cost of this treatment is low. Based on the above information, WS appears to us to be a good candidate for future ALS trials.

ALSUntangled #72: Insulin.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.

Dietary patterns and associated lifestyle factors among university students in Qatar.

Objective: We aimed to investigate the association between university students' dietary patterns, their demographics and lifestyle in a cross-sectional study in Qatar. Participants: 370 students in eight universities in Qatar enrolled between February 2017 and February 2018. Methods: Based on a structured questionnaire, dietary patterns were identified using principal component analysis, and their associations with student characteristics were assessed using logistic regression. Results: Four dietary patterns were identified. The 'fast food' pattern was associated with being younger and male (p-values ≤ 0.1). The 'traditional diet' pattern was associated with not skipping meals or eating when bored (p-values = 0.1). The 'healthy diet' pattern was associated with regular exercise and having time to eat healthy foods (p-values ≤ 0.01). The 'protein shake' pattern was associated with being male and engaging in more vigorous physical activity (p-values ≤ 0.01). Conclusions: Our findings provide a roadmap for the prioritization of population-specific interventions in university students within Qatar and the region.

Factors associated with perceived stress in Middle Eastern university students.

Objective: University students face high levels of stress-related factors, such as an unfamiliar environment, challenging workload, and uncertainty about their ability to succeed. Participants: A total of 370 students in Qatar who consented to participate between February 2017 and February 2018. Methods: This cross-sectional study assessed perceived stress [using a validated 4-point perceived stress scale (PSS-4)], as well as diet, exercise, body mass index, sleep, and life satisfaction. Results: Among students aged 18-39 (mean = 20.1 ± 3.0 years), PSS-4 scores varied between 0 and 16 (mean = 7.4 ± 3.4). Elevated stress was significantly associated with female sex, country of origin, residing off-campus, eating when bored, lack of self-discipline, disturbed sleep, and low levels of life satisfaction. Furthermore, students with PSS-4 scores above the median level were 2.3 times likelier to report difficulty concentrating on academic work. Conclusion: Elevated stress levels are present in university students in Qatar. Strengthening coping skills may improve health and academic performance.

Effect of Reperfusion Therapies on Incidence of Early Post-Stroke Seizures.

Objective: This study aimed to determine the effect of reperfusion therapies on the occurrence of early post-stroke seizures (PSS) in patients with acute ischemic stroke (AIS). Background: Reperfusion therapies are paramount to the treatment of stroke in the acute phase. However, their effect on the incidence of early seizures after an AIS remains unclear. Design and Methods: The stroke database at Hamad Medical Corporation was used to identify all patients who received reperfusion therapies for AIS from 2016 to 2019. They were matched with patients of similar diagnosis, gender, age, and stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS) who did not receive such treatment. The rates of early PSS were calculated for each group. Results: The results showed that 508 patients received reperfusion therapies (342 had IV thrombolysis only, 70 had thrombectomies only, and 96 had received both), compared with 501 matched patients receiving standard stroke unit care. Patients who received reperfusion therapies were similar to their matched controls for mean admission NIHSS score (9.87 vs. 9.79; p = 0.831), mean age (53.3 vs. 53.2 years; p = 0.849), and gender distribution (85 vs. 86% men; p = 0.655). The group receiving reperfusion therapies was found to have increased stroke cortical involvement (62 vs. 49.3%, p < 0.001) and hemorrhagic transformation rates (33.5 vs. 18.6%, p < 0.001) compared with the control group. The rate of early PSS was significantly lower in patients who received reperfusion therapies compared with those who did not (3.1 vs. 5.8%, respectively; p = 0.042). When we excluded seizures occurring at stroke onset prior to any potential treatment implementation, the difference in early PSS rates between the two groups was no longer significant (2.6 vs. 3.9%, respectively; p = 0.251). There was no significant difference in early PSS rate based on the type of reperfusion therapy either (3.2% with thrombolysis, 2.9% with thrombectomy, and 3.1% for the combined treatment, p = 0.309). Conclusions: Treatment of AIS with either thrombectomy, thrombolysis, or both does not increase the risk of early PSS.

Strategies in the Management of Adolescent Obesity.

PURPOSE OF REVIEW: We review the current options to manage adolescent obesity which include nutrition, physical activity, behavior modification, sleep management, pharmacotherapy and surgery. Since lifestyle interventions alone are often not effective in adolescents, a multi-disciplinary treatment approach is necessary in management. RECENT FINDINGS: Medications (often used off-label) and metabolic/bariatric surgery are effective treatment strategies to treat adolescents with severe obesity. SUMMARY: The use of pharmacotherapy and surgery is limited due to lack of pediatric obesity tertiary care centers. With more centers, the treatment of adolescent obesity will improve and aid to decrease the prevalence of adult obesity.

Comparison of Short and Long-Term Outcomes of Metabolic and Bariatric Surgery in Adolescents and Adults.

Objective: We sought to compare the short and long-term outcomes of MBS in adolescents vs. adults who have undergone a Roux-en-Y gastric bypass (RYGB) or Sleeve gastrectomy (SG). Design: Retrospective cohort study. Setting: Single tertiary care academic referral center. Participants: One hundred fifty adolescent (≤ 21-years) and adult (>21-years) subjects with severe obesity between 15 and 70 years of age who underwent RYGB or SG. Outcomes: Metabolic parameters, weight and height measures were obtained pre-and post-surgery (at 3 and 6 months, and then annually for 4 years). Results: Median pre-surgical body mass index (BMI) was higher in adolescents (n = 76) vs. adults (n = 74): 50 (45-57) vs. 44 (40-51) kg/m2 (p < 0.0001). However, obesity related complications were greater in adults vs. adolescents: 66 vs. 21% had hypertension, 68 vs. 28% had dyslipidemia, and 42 vs. 21% had type 2 diabetes mellitus (all p < 0.010). % BMI reduction and % weight loss (WL) were greater in adolescents vs. adults at all time points (p < 0.050). %WL was higher in adolescents who underwent SG at each time point (p < 0.050), and trended higher among adolescents who underwent RYGB (p = 0.060), compared to adults with the respective procedure. Follow-up data showed greater resolution of type 2 diabetes and hypertension in adolescents than adults (87.5 vs. 54.8%; p = 0.04, and 68.7 vs. 35.4%; p = 0.040). Conclusion: Adolescents compared to adults had greater reductions in BMI and weight, even at 4 years, and greater resolution of type 2 diabetes and hypertension. Earlier intervention in the treatment of severe obesity with MBS may lead to better outcomes.

Obesity and Hypogonadism-A Narrative Review Highlighting the Need for High-Quality Data in Adolescents.

The prevalence of obesity continues to rise in adult and pediatric populations throughout the world. Obesity has a direct impact on all organ systems, including the reproductive system. This review summarizes current knowledge about the effects of obesity on the male reproductive system across age, highlighting the need for more data in children and adolescents. Male hypogonadism is commonly seen in patients with obesity and affects the onset, duration, and progression of puberty. Different pathophysiologic mechanisms include increased peripheral conversion of testosterone to estrone and increased inflammation due to increased fat, both of which lead to suppression of the hypothalamic-pituitary-gonadotropin (HPG) axis and delayed development of secondary sexual characteristics in adolescent males. Evaluation of the HPG axis in obesity includes a thorough history to exclude other causes of hypogonadism and syndromic associations. Evaluation should also include investigating the complications of low testosterone, including increased visceral fat, decreased bone density, cardiovascular disease risk, and impaired mood and cognition, among others. The mainstay of treatment is weight reduction, but medications such as testosterone and clomiphene citrate used in adults, remain scarcely used in adolescents. Male hypogonadism associated with obesity is common and providers who care for adolescents and young adults with obesity should be aware of its impact and management.

MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways.

MicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here, we describe a neuroprotective function of miR-132, the miRNA most significantly downregulated in neurons in Alzheimer's disease. We demonstrate that miR-132 protects primary mouse and human wild-type neurons and more vulnerable Tau-mutant neurons against amyloid ß-peptide (Aß) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopathies, promotes neurite elongation and branching, and reduces neuronal death. Similarly, miR-132 attenuates PHF-Tau pathology and neurodegeneration, and enhances long-term potentiation in the P301S Tau transgenic mice. The neuroprotective effects are mediated by direct regulation of the Tau modifiers acetyltransferase EP300, kinase GSK3ß, RNA-binding protein Rbfox1, and proteases Calpain 2 and Caspases 3/7. These data suggest miR-132 as a master regulator of neuronal health and indicate that miR-132 supplementation could be of therapeutic benefit for the treatment of Tau-associated neurodegenerative disorders.