Sex differences in the association between vascular factors and cognitive outcomes remain unclear. We aimed to investigate the associations of blood pressure metrics (hypertension, systolic blood pres Show more
Sex differences in the association between vascular factors and cognitive outcomes remain unclear. We aimed to investigate the associations of blood pressure metrics (hypertension, systolic blood pressure [SBP), pulse pressure, ankle and brachial pressures, and ankle to brachial pressure index [ABI]) with the risk of cognitive decline and dementia. We conducted a population-based longitudinal analysis using data from the Atherosclerosis Risk in Communities (ARIC) study (begun in 1987-1989) in the United States. We analyzed a total of 12,268 participants aged 45-64 years who had validated exposure measurements, cognitive function tests (first administrated 1990-1992), and followed up for incidence of dementia through December 2019. Cognitive function was assessed using the Digit Symbol Substitution Test, the Delayed Word Recall Test, and the Word Fluency Test. Dementia cases were identified through a standardized clinical evaluation process, mostly adjudicated by expert reviewers. We performed sex-stratified analyses to examine the associations of blood pressure metrics and APOE ε4 allele with the risk of cognitive decline and dementia. Over a median follow-up of 26.4 years, 2698 participants developed dementia. Women aged 55-64 had a significantly higher incidence of dementia than men aged 55-64 (14.8 vs. 11.8 per 1000 person-years; p < These findings highlight notable sex differences in the association between vascular factors and cognitive decline and dementia risk. Women appear more vulnerable to both genetic and vascular risk factors, emphasizing the need for sex-specific approaches in research, prevention, and intervention strategies for cognitive impairment. NIH. Show less
Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effe Show more
Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effects, which often lead to treatment discontinuation and subsequent relapse in patients with LaBCC. Prolonged remission was previously reported in patients with LaBCCs who underwent surgical debulking before starting vismodegib. In this study, we enrolled 4 patients with LaBCC who underwent debulking followed by vismodegib therapy to assess their clinical outcomes and analyze the cutaneous molecular changes occurring as a result of surgical intervention. After LaBCC debulking, patients underwent a punch biopsy of residual basal cell carcinoma tissue 1 week later. RT-qPCR analysis of 24 Notch and Wnt signaling-associated genes revealed elevated Show less