Amyloid-Beta (Aβ) D7H Mutation Increases Oligomeric Aβ42 and Alters Properties of Aβ-Zinc/Copper Assemblies

Amyloid precursor protein (APP) mutations associated with familial Alzheimer's disease (AD) usually lead to increases in amyloid β-protein (Aβ) levels or aggregation. Here, we identified a novel APP mutation, located within the Aβ sequence (AβD7H), in a Taiwanese family with early onset AD and explored the pathogenicity of this mutation. Cellular and biochemical analysis reveal that this mutation increased Aβ production, Aβ42/40 ratio and prolonged Aβ42 oligomer state with higher neurotoxicity. Because the D7H mutant Aβ has an additional metal ion-coordinating residue, histidine, we speculate that this mutation may promote susceptibility of Aβ to ion. When co-incubated with Zn2+ or Cu2+, AβD7H aggregated into low molecular weight oligomers. Together, the D7H mutation could contribute to AD pathology through a “double punch” effect on elevating both Aβ production and oligomerization. Although the pathogenic nature of this mutation needs further confirmation, our findings suggest that the Aβ N-terminal region potentially modulates APP processing and Aβ aggregation, and further provides a genetic indication of the importance of Zn2+ and Cu2+ in the etiology of AD

The Effects of a Guided Mindful Walk on Mental Health in University Students

International Journal of Exercise Science 17(5): 590-601, 2024. College campuses in the United States are experiencing high levels of mental distress without adequate psychological resources to address the need. In addition, the majority of university students do not meet the physical activity guidelines for mental and physical health. Effective and time efficient resources are needed to address poor mental health and low physical activity among university students on college campuses. Mindful walking may be a promising solution. The purpose was to 1) measure change in mental health and 2) estimate physical activity from participation in a guided mindful walk in a diverse student sample. Students participated in a mindful walking route which included seven stops (0.85 miles) during the Spring 2022 semester. Undergraduate students (n = 44) were mean ± SD age 20.9 ± 3.8 years and 68% female. Validated surveys were given pre- and post-participation measuring mental health constructs of state mindfulness (Toronto Mindfulness Scale; TMS), state anxiety (visual analogue scale), and state stress (Short Stress State Questionnaire; SSSQ). Physical activity was estimated via steps on a Yamax pedometer worn at the hip. After the guided mindful walk, total state mindfulness score significantly improved (mean ± SD) (pre: 27.5 ± 8.2, post: 32.8 ± 9.5; p \u3c 0.001); state anxiety significantly decreased (pre: 3.7 ± 2.4, post: 2.4 ± 2; p \u3c 0.0001) and total state stress score was reduced (pre: 66.1 ± 10.7, post: 63.4 ± 8.3; p = 0.03). Physical activity averaged 1,726 ± 159 steps. Completion of a guided mindful walk can reduce anxiety and stress, while increasing mindfulness among university students

Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.

BACKGROUND: The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. METHODS: An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. RESULTS: The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. CONCLUSION: The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575