Naps and cardiovascular disease risk in different age and sex groups: evidence from a large community cohort.

STUDY OBJECTIVES: This study examined the relationship between naps and cardiovascular disease (CVD) events or death in different age and sex groups. METHODS: A total of 3,069 participants stratified by age (< 65, 65-74, and ≥ 75 years old) and sex, underwent Cox regression analysis to assess nap's impact on CVD risk. Restricted cubic spline plots were used for dose-response relationships. RESULTS: Significant age-stratified interactions were found when exploring the associations between nap frequency or duration and CVD events (Pinteraction = .001, .036, respectively). Individuals younger than 65 years with higher nap frequency or longer nap duration had a significantly increased risk of CVD events (P < .001, P = .001, respectively). The age group of 65-74 years showed significant associations between CVD events and nap frequency or nap duration (P = .017, .016, respectively), together with nap duration and CVD deaths (P = .008). In the subgroup of females aged 65-74, significant associations were found between nap frequency or duration and CVD events (P = .006, .002, respectively). Nap frequency or duration was also significantly associated with CVD deaths (P = .005, .010 respectively). CONCLUSIONS: This study underscores a noteworthy correlation between a higher frequency or longer duration of daytime nap and an increased susceptibility to CVD among individuals aged 65-74 years, particularly in females. However, further research is needed to better understand the underlying mechanisms. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Sleep Heart Health Study; URL: https://clinicaltrials.gov/ct2/show/study/NCT00005275; Identifier: NCT00005275. CITATION: Chen C, Guo Q, Cheng Y, Lan Y, Cheng D, Huang J. Naps and cardiovascular disease risk in different age and sex groups: evidence from a large community cohort. J Clin Sleep Med. 2024;20(8):1339-1348.

Leptin alleviates endoplasmic reticulum stress induced by cerebral ischemia/reperfusion injury via the PI3K/Akt signaling pathway.

BACKGROUND: Cerebral ischemic/reperfusion injury (CIRI) is a key factor for the prognosis of ischemic stroke (IS), the leading disease in terms of global disability and fatality rates. Recent studies have shown that endoplasmic reticulum stress (ERS) may be a target against CIRI and that leptin, a peptide hormone, has neuroprotective activity to mitigate CIRI. METHODS: An in vitro CIRI model was induced in primary cortical neurons by oxygen-glucose deprivation and reoxygenation (OGD/R) after pretreatment with LY294002 (10 µmol/L) and/or leptin (0.4 mg/L), and cell viability, neuronal morphology and endoplasmic reticulum (ER) dysfunction were evaluated. An in vivo CIRI model was established in rats by middle cerebral artery occlusion and reperfusion (MCAO/R) after the injection of LY294002 (10 µmol/L) and/or leptin (1 mg/kg), and neurological function, infarct volume, cerebral pathological changes, the expression of ERS-related proteins and cell apoptosis were examined. RESULTS: In vitro, leptin treatment improved the cell survival rate, ameliorated neuronal pathological morphology and alleviated OGD/R-induced ERS. In vivo, administration of leptin significantly reduced the infarct volume, neurological deficit scores and neuronal apoptosis as well as pathological alterations. In addition, leptin suppressed MCAO/R-induced ERS and may decrease apoptosis by inhibiting ERS-related death and caspase 3 activation. It also regulated expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax in the cortex. Furthermore, the inhibitory effect of leptin on ERS was significantly decreased by the effective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. CONCLUSIONS: These results confirm that ERS plays an important role in CIRI and that leptin can inhibit the activation of ERS through the PI3K/Akt pathway, thereby alleviating CIRI. These findings provide novel therapeutic targets for IS.

The independent risks and specific biomarker of breast cancer-related ischemic stroke.

AIM: This retrospective study was designed to investigate the independent risks and specific biomarker for breast cancer-related ischemic stroke (BCRS). METHODS: Clinical features and laboratory findings were compared between BCRS group and breast cancer group without stroke, and further multivariate analyses were performed to predict independent risks factors for BCRS patients. A receiver operator characteristic (ROC) curve analysis was configured to estimate the diagnostic efficacy of each independent risk and the product of these risks and to obtain the optimal cut-off value of diagnosis, which was termed the BCRS Index. RESULTS: BCRS patients had elevated plasma D-dimer and CA153 levels and platelet-to-lymphocyte ratio (PLR), as well as more patients received endocrine therapy (all p ＜ 0.05). Moreover, multivariate analysis revealed that D-dimer levels (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001-1.003; p = 0.000), CA153 levels (OR: 1.005; 95% CI: 1.001-1.008; p = 0.007), PLR (OR: 1.010; 95% CI: 1.004-1.015; p = 0.001), and endocrine therapy (OR: 1.268; 95% CI: 1.087-1.479; p = 0.003) were identified as independent risks of BCRS. Furthermore, ROC analysis displayed that the product of risks had the best diagnostic efficacy, of which the area under the curve was 0.846 ± 0.28. The optimum cut-off point was 2.37 × 106/mL, which was termed the BCRS Index with higher diagnostic accuracy and validity. CONCLUSIONS: Endocrine therapy, as well as elevated plasma D-dimer and CA153 levels and PLR values may be independent risks for BCRS. Furthermore, BCRS Index should be served as a novel specific biomarker for BCRS, which is useful to distinguish BCRS for clinicians.

Recurrent episodes of reversible posterior leukoencephalopathy in three Chinese families with GJB1 mutations in X-linked Charcot-Marie-tooth type 1 disease: cases report.

BACKGROUND: The X-linked form of Charcot-Marie-Tooth disease type 1 (CMTX1) is an inherited peripheral neuropathy that arises in patients with mutations in the gap-junction beta-1 gene (GJB1). CASE PRESENTATION: Three young male patients from Southern China with pes cavus experienced multiple episodes of transient central nervous system (CNS) dysfunction. Three patients all had reversible posterior leukoencephalopathy as detected by brain diffusion-weighted magnetic resonance imaging (MRI-DWI). Nerve conduction velocity (NCV) showed sensorimotor polyneuropathy with mixed demyelinating and axonal features. Genetic testing indicated a c.425G > A (p.Arg142Glu) or c.563 C > T (p.Thr188Ile) or c.103G > C (p.Val35Leu) mutation in GJB1. The unique feature of this report is the identification of two novel mutations: c.563 C > T and sc.103G > C of the GJB1 gene detected in two families respectively. Another unique feature is that peripheral neuropathy symptoms in the three patients were insidious and found at the onset of CNS symptoms. CONCLUSIONS: Posterior leukoencephalopathy is involved in CMTX1 patients. The white matter changes in MRI of CMTX1 patients are reversible and recover later than CNS symptoms.

Specific Biomarkers of Prostate Cancer-Associated Ischemic Stroke: A Case-Control Study.

BACKGROUND Ischemic stroke in cancer patients is associated with poor prognosis. However, the specific biomarkers of cancer-associated ischemic stroke (CaIS) have not been well defined. MATERIAL AND METHODS A retrospective study was conducted on PCaIS patients. Clinical data and laboratory and imaging findings were collected. Multivariable logistic regression analysis was used to analyze the independent risk factors for PCaIS. A multiple model combining the independent risk factors of PCaIS was developed using the receiver operating characteristic (ROC) and area under the ROC curve (AUC). RESULTS A total of 83 PCaIS patients and 83 prostate cancer (PCa) patients were included. PCaIS patients had higher levels of D-dimer, neutrophil-to-lymphocyte ratio (NLR), and total prostate-specific antigen (T-PSA). In the multivariate analysis, D-dimer [OR=1.001, 95% CI: 1.00,1.00, P=0.002], NLR [OR=1.12, 95% CI: 1.04,1.22, P=0.005], and T-PSA [OR=6.275, 95% CI: 2.57,15.31, P<0.001] were independent risk factors of PCaIS. Additionally, the AUC of the multiple model of PCaIS was 0.815 (95% CI, 0.750-0.869), with sensitivity of 81.71% and specificity of 70.21%. CONCLUSIONS Elevated levels of D-dimer and T-PSA and increased NLR are independent risk factors of PCaIS. The multiple model of PCaIS can be a specific biomarker and is a reliable predictor of development of PCaIS.

Leptin attenuates cerebral ischemic injury in rats by modulating the mitochondrial electron transport chain via the mitochondrial STAT3 pathway.

BACKGROUND: According to recent studies, leptin may exert a neuroprotective function by affecting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). During stress, STAT3 regulates mitochondrial oxidative stress and reduces apoptosis. OBJECTIVE: In the present study, we hypothesized that leptin increases STAT3 phosphorylation in the mitochondria and protects against mitochondrial oxidative stress in rats subjected to permanent middle cerebral artery occlusion (MCAO). RESULTS: Leptin reduced reactive oxygen species (ROS) production, and we confirmed that the mechanism underlying this change involved the enzymatic activities of mitochondrial respiratory chain complexes I and II. In addition, leptin increased the level of STAT3 Ser727 phosphorylation in the mitochondria. CONCLUSIONS: Based on these results, leptin may regulate mitochondrial respiratory chain enzymatic activities via mitochondria-targeted STAT3 to reduce ROS production and protect brain tissues from mitochondrial oxidative stress during cerebral ischemia.

Cerebral hemorrhage as the initial manifestation in patients with systemic cancer.

BACKGROUND: Cerebral hemorrhage as well as ischemic stroke is one of the common complications among patients with cancer. Ischemic stroke could be the initial manifestation in some patients with cancer. Meanwhile, some patients with cancer also could present cerebral hemorrhage as the initial manifestation, and further studies are required to determine whether these patients have their unique clinical features. AIM: To investigate the clinical features and underlying pathogenesis of concealed systemic cancer patients with cerebral hemorrhage as the initial manifestation. METHODS: The clinical data of patients with concealed systemic cancer who presented cerebral hemorrhage as the initial manifestation registered at the First Affiliated Hospital of Guangxi Medical University from January 2010 to December 2015 were prospectively collected and analyzed. RESULTS: Seventeen systemic cancer patients with cerebral hemorrhage as the initial manifestation (0.02%) were ultimately enrolled from 8,326 patients with cerebral hemorrhage. Three patients had traditional risk factors, but the other 14 patients did not. The common subtypes of malignancy were lung cancer, liver cancer, gastric carcinoma, rectal cancer and melanoma. Most patients (11/17, 64.7%) had elevated plasma levels of cancer biochemical markers, including cancer antigen (CA)125, CA153 and CA199, carcino-embryonic antigen, and alpha fetal protein. Coagulopathy was observed in 15 patients. CONCLUSION: The concealed systemic cancer patients with cerebral hemorrhage as the initial manifestation may lack conventional vascular risk factors but did present coagulopathy and elevated plasma levels of cancer biochemical markers. Coagulopathy might be responsible for the cerebral hemorrhage.

Potential Pathogenesis and Biomarkers of Kidney Cancer-Related Stroke.

BACKGROUND Stroke risk and stroke recurrence are increased in cancer patients, but the pathogenesis and biomarkers of kidney cancer-related stroke (KCS) are generally unclear. The aim of the present research was to investigate the pathogenesis and plasma biomarkers of kidney cancer-related stroke. MATERIAL AND METHODS A retrospective review was conducted on acute stroke patients with kidney cancer (KC) who were admitted to the hospital between January 2006 and December 2015. A total of 106 patients with KCS (active KC patients with acute stroke but without conventional vascular risks) were identified. In addition, 106 age- and sex-matched patients with KC alone were recruited. RESULTS KCS patients had higher plasma D-dimer, cancer antigen (CA) 125, and CEA levels and greater proteinuria levels than did KC patients. Multiple logistic regression analysis showed that the risk of stroke in patients with KC increased independently by 0.8% (odds ratio [OR] 1.008; 95% confidence interval [CI] 1.002, 1.013; p=0.004) with a 1 ng/mL increase in D-dimer levels, by 1.2% (OR 1.012; 95% CI 1.007, 1.018; p=0.000) with a 1 U/mL increase in CA125, by 2.5% (OR 1.025; 95% CI 1.012, 1.038; p=0.000) with a 1 U/mL increase in CEA by 1.4% (OR 1.014; 95% CI 1.005, 1.024; p=0.004) with a 1 mg increase in urine protein in 24 hours. CONCLUSIONS Elevated plasma D-dimer, CA125 and CEA levels, and increased urine protein levels might lead to hypercoagulability and then KCS; however, they may also be biomarkers of KCS.

Associations of TNFα-308G/A and TNFα-238G/A Polymorphisms with Ischemic Stroke in East Asians and Non-East Asians: A Meta-Analysis.

AIMS: Two well-characterized polymorphisms in the tumor necrosis factor (TNF) gene, TNFα-308G/A and TNFα-238G/A, are thought to play important roles in the etiology and pathogenesis of ischemic stroke. Due to ethnic diversity, studies of the associations between these polymorphisms and ischemic stroke are inconclusive. Thus, we conducted a meta-analysis to derive more precise estimates of these associations in East Asians and non-East Asians. MATERIALS AND METHODS: We searched relevant publications in the PubMed, Embase, and Medline databases. A total of 18 studies with 8075 patients and 8217 controls were included. The odds ratios (OR) and 95% confidence intervals (CIs) were evaluated to identify associations. RESULTS: Analyses of the full dataset failed to identify any significant association between ischemic stroke and the TNFα-308G/A (A vs. G: OR = 0.86, 95% CI: 0.72-1.02, p = 0.08) or TNFα-238G/A (A vs. G: OR = 0.94, 95% CI: 0.67-1.32, p = 0.72) polymorphism. In subgroup analysis by ethnicity, TNFα-308G/A was found to be a protective factor (A vs. G: OR = 0.69, 95% CI: 0.56-0.85, p = 0.01) against ischemic stroke in the East Asians. No significant association was detected between ischemic stroke risk and TNFα-238G/A in the East Asians (A vs. G: OR = 0.82, 95% CI: 0.57-1.16, p = 0.26) or non-East Asians (A vs. G: OR = 1.61, 95% CI: 0.90-2.88, p = 0.11). CONCLUSIONS: The results of this meta-analysis suggest that there is no significant relationship between ischemic stroke and TNFα-308G/A or TNFα-238G/A. However, according to subgroup analysis of East Asians, TNFα-308G/A is a protective factor against ischemic stroke.