Citations

Objectives Ruptured anterior communicating artery (ACoA) aneurysms occur more frequently in men. The purpose of the study was to investigate sex difference in aneurysm morphologies and clinical outcomes in patients with ruptured ACoA aneurysms. Setting A tertiary referral hospital. Participants A total of 574 consecutive patients with ACoA aneurysms were admitted to our hospital from December 2007 to February 2015. In all, 474 patients (257 men and 217 women) with ruptured ACoA aneurysms were included in the study. Main outcome measures Aneurysm morphologies were measured using computed tomographic angiography and clinical outcomes were measured with Glasgow coma score at discharge. Results The aneurysm sizes (p=0.001), aneurysm heights (p=0.011), size ratios (p<0.001), flow angles (p=0.047) and vessel angles (p=0.046) were larger in the male patients than in the females. The female patients more often had larger vessel sizes (p=0.002). Multivariate logistic analysis revealed that significant differences in aneurysm morphologies between men and women were aneurysm size (OR 1.1, 95% CI 1.0 to 1.3; p=0.036), aneurysm height (OR 0.8, 95% CI 0. to 0.9; p=0.006) and size ratio (OR 1.4, 95% CI 0.5 to 1.7; p=0.001). There were no statistically significant differences in the outcomes between men and women (OR 1.0, 95% CI 0.6 to 1.7, p=0.857). Conclusions The men were independently associated with larger aneurysm sizes, greater aneurysm heights and larger size ratios. Sex was not a risk factor for poor outcome in patients with ruptured ACoA aneurysms.

Abstract Background: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by multitudes of expanding renal cysts associated with mononuclear interstitial infiltrates. Monocyte chemotactic protein-1 is produced in the kidneys and excreted in the urine (uMCP1) of these patients in increased amounts. In the TEMPO 3:4 trial, tolvaptan slowed the rate of increase in total kidney volume (TKV) and the rate of decline in estimated glomerular filtration rate (eGFR). In a sub-analysis, we determined whether tolvaptan administration for up to 3 years changed the urinary excretion of MCP-1 referenced to creatinine in 869 treated subjects compared with 438 placebo subjects. Methods: Treatment group differences of uMCP1 at 0.75, 12, 24 and 36 months were evaluated by ANCOVA with factor of treatment and covariate baseline. Results: At baseline, mean uMCP1 was 429 ± 224 pg/mg in the tolvaptan and 434 ± 233 pg/mg in the placebo groups, ∼4-fold greater than normal. Log uMCP1 associated positively with log TKV (r = 0.2645, P &lt; 0.0001) and negatively with eGFR (r = −0.1555 P &lt; 0.0001) and fasting urine osmolality (r = −0.1933, P &lt; 0.0001). Tolvaptan reduced uMCP1 13.8 ± 4.4% (P &lt; 0.0001) below placebo-treated subjects at 24 months and 14.4 ± 3.7% (P &lt; 0.0001) at 36 months, and to the same extent in females and males. The effect of tolvaptan on uMCP1 excretion at 36 months extended across CKD Stage 1 (11.1 ± 6.4%, P = 0.0595), CKD 2 (13.9 ± 5.4%, P = 0.0050) and CKD 3 (21.4 ± 8.0%, P = 0.0020). Conclusion: Tolvaptan, administered for 3 years to patients with ADPKD, caused a sustained reduction in the urinary excretion of MCP-1 relative to placebo.

Background Women electing endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) report higher symptom burden but have lower computed tomography (CT) scores. Gender‐specific analysis of outcomes from ESS therefore merits further study. The objective of this work was to study gender‐specific differences in outcomes from ESS for CRS by analyzing preoperative and postoperative 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Methods Data from adult CRS patients electing ESS (2011‐2013) were retrospectively collected. SNOT‐22 total, rhinologic/nonrhinologic subdomain, and individual item scores were analyzed for gender‐specific differences. Results Two hundred and forty‐eight patients met study criteria (mean age 55.4 years; 49.6% female). Preoperatively, mean Lund‐Mackay CT score was 11.1; average total SNOT‐22 score was 41.9. Compared to men, women had lower CT score (10.2 vs 12.0; p = 0.004) but higher total SNOT‐22 score (44.7 vs 39.1; p = 0.02). Both genders showed significant improvement in total SNOT‐22 scores at 3, 6, 12, and 24 months following ESS ( p < 0.001), with largely similar slopes of improvement. The greatest improvement occurred at 3 months (SNOT‐22 decreased by 25.4 points), with stable improvement after 12 months (SNOT‐22 decreased by 21.3 points). Higher total SNOT‐22 scores in females were noted preoperatively and until 6 months post‐ESS; these were driven by rhinologic and nonrhinologic‐otolaryngic subdomain items. No gender differences in anxiety/depression prevalence or psychological subdomain scores were noted preoperatively or postoperatively. Conclusion Both male and female CRS patients showed significant and durable symptom relief following ESS. Women reported higher symptom burden prior to surgery, and in the early postoperative period. However, after 1‐year post‐ESS, both genders showed similar symptom scores. The trend and magnitude of improvement were similar in both genders.

Summary Background and Purpose Sprawling ( Swl ) is a radiation‐induced mutation which has been identified to have a nine base pair deletion in dynein heavy chain 1 (DYNC1H1: encoded by a single gene Dync1h1 ). This study is to investigate the phenotype and the underlying mechanism of the Dync1h1 mutant. Methods and Results To display the phenotype of Swl mutant mice, we examined the embryos of homozygous ( Swl/Swl ) and heterozygous ( Swl /+) mice and their postnatal dorsal root ganglion (DRG) of surviving Swl /+ mice. The Swl /+ mice could survive for a normal life span, while Swl/Swl could only survive till embryonic (E) 8.5 days. Excessive apoptosis of Swl/ + DRG neurons was revealed during E11.5–E15.5 days, and the peak rate was at E13.5 days. In vitro study of mutated DRG neurons showed impaired retrograde transport of dynein‐driven nerve growth factor (NGF). Mitochondria, another dynein‐driven cargo, demonstrated much slower retrograde transport velocity in Swl/+ neurons than in wild‐type (WT) neurons. Nevertheless, the Swl , Loa, and Cra mutations did not affect homodimerization of DYNC1H1. Conclusion The Swl/Swl mutation of Dync1h1 gene led to embryonic mal‐development and lethality, whereas the Swl/+ DRG neurons demonstrated deficient retrograde transport in dynein‐driven cargos and excessive apoptosis during mid‐ to late‐developmental stages. The underlying mechanism of the mutation may not be due to impaired homodimerization of DYNC1H1.

Abstract Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo. We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro. Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1–FOXO1–MMP-2 axis. Cancer Prev Res; 9(7); 567–80. ©2016 AACR.

Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focuses on novel and unique aspects of cardiovascular health in women and sex differences as they relate to clinical practice in the prevention, diagnosis, and treatment of cardiovascular disease. This review also provides current approaches to the evaluation and treatment of acute coronary syndromes that are more prevalent in women, including myocardial infarction associated with nonobstructive coronary arteries, spontaneous coronary artery dissection, and stress-induced cardiomyopathy (Takotsubo Syndrome). Other cardiovascular disease entities with higher prevalence or unique considerations in women, such as heart failure with preserved ejection fraction, peripheral arterial disease, and abdominal aortic aneurysms, are also briefly reviewed. Finally, recommendations for cardiac rehabilitation are addressed.