Characterizing cerebrospinal fluid mobility using heavily T2-weighted 3D fast spin echo (FSE) imaging with improved multi-directional diffusion-sensitized driven-equilibrium (iMDDSDE) preparation.

Cerebrospinal fluid (CSF) flow patterns and their relationship with arterial pulsation can depict the function of glymphatic system (GS). We propose an improved multi-directional diffusion-sensitized driven-equilibrium (iMDDSDE) prepared heavily T2-weighted 3D FSE (iMDDSDE-HT2) magnetic resonance imaging (MRI) method to noninvasively assess the mobility (MO) of CSF distributed in the ventricles and perivascular spaces (PVS). This method could obtain 3D high resolution (1 mm isotropic) imaging of CSF MO with full brain coverage within five min and distinguish the CSF MO across different pulse phases using a peripheral pulse unit (PPU). The MO curves had the largest amplitude value in the PVS of middle cerebral artery (11.11 × 10-9 m2/s) and the largest amplitude growth rate in the posterior cerebral artery (189%). The average coefficient of variations (CVs) in non-pulse trigger and pulse phase 1 and 3 were 0.11, 0.10 and 0.09 respectively. The MO in older healthy participants was lower compared to the young participants, and the MO in cerebral major artery stenosis patients with acute ischemia stroke (AIS) were lower compared to those without AIS in several ventriclar ROIs (P < 0.05). This sequence is a clinically feasible method to effectively evaluate CSF flow patterns in human brain.

Disturbed meningeal lymphatic function associated with malignancy and progression in patients with intracranial malignant tumors.

BACKGROUND: Meningeal lymphatic vessels (mLVs) have proven to bear a relationship with tumor immunity and therapeutic efficacy of intracranial malignant tumors in pre-clinical animal studies. We aimed to explore the association between mLV function and intracranial malignant tumors in clinical participants. METHODS: The participants were allocated to a control group or a group of patients with intracranial tumors. Dynamic enhanced magnetic resonance was used to evaluate the wash-in and wash-out functions of mLVs around the superior sagittal sinus and the sigmoid sinus. FINDINGS: A total of 246 individuals were recruited for our study. The area under curve and wash-in rate of mLVs in the intracranial tumor group were higher than in the control group (2,749 vs. 2,110, p < 0.001 and 3.72 vs. 2.87, p < 0.001, respectively). The wash-out ratio of mLVs was lower in the intracranial tumor group than in the control group (0.65 vs. 0.73, p < 0.001). Decreased wash-out of mLVs was associated with tumor progression (ß = -0.118; p < 0.001). High-grade glioma and isocitrate dehydrogenase wild type were associated with a lower mLV wash-out function (ß = -0.057, p = 0.044 and ß = -0.069, p = 0.047, respectively). CONCLUSIONS: Intracranial malignant tumors were associated with elevated wash-in function and decreased wash-out function of mLVs. High-grade glioma and isocitrate dehydrogenase wild type were associated with low mLV wash-out function, and long-term decreased mLV wash-out function was a risk factor for tumor progression. FUNDING: There was no funding.

Melatonin alleviates depression-like behaviors and cognitive dysfunction in mice by regulating the circadian rhythm of AQP4 polarization.

Depression is a common chronic psychiatric illness, which is resistant to medical treatments. While melatonin may alleviate certain depression symptoms, evidence for its efficacy against core symptoms is lacking. Here, we tested a mechanism whereby melatonin rescues the behavioral outcomes of the chronic unpredictable mild stress (CUMS) mouse model of depression. CUMS mice showed depressive behaviors to tail suspension, open field behavior, and sucrose preference test, and cognitive dysfunction in the Morris water maze. Impairments in these measures were relieved by melatonin treatment. Moreover, CUMS mice had impaired glymphatic function across the sleep-wake cycle due to the astrocytic loss and disturbance of circadian regulation of the polarized expression of aquaporin-4 (AQP4) water channels in perivascular astrocytes. EEG results in CUMS mice showed a reduced total sleep time and non-rapid eye movement (NREM) sleep, due to sleep fragmentation in the light phase. CUMS mice lost the normal rhythmic expressions of circadian proteins Per2, Cry2, Bmal1, Clock, and Per1. However, the melatonin treatment restored glymphatic system function and the polarization of AQP4, while improving sleep structure, and rectifying the abnormal expression of Per2, Bmal1, Clock, and Per1 in CUMS mice. Interestingly, Per2 expression correlated negatively with the polarization of AQP4. Further studies demonstrated that Per2 directed the location of AQP4 expression via interactions with the α-dystrobrevin (Dtna) subunit of AQP4 in primary cultured astrocytes. In conclusion, we report a new mechanism whereby melatonin improves depression outcomes by regulating the expression of the circadian protein Per2, maintaining the circadian rhythm of astrocytic AQP4 polarization, and restoring glymphatic function.

Sleep duration, daytime napping, and risk of incident stroke: Nuances by metabolic syndrome from the China health and retirement longitudinal study.

Background and purpose: The relationship between sleep duration and stroke are inconclusive in China, especially in those individuals with metabolic syndrome. We aimed to investigate the association between sleep duration and incident stroke in participants with metabolic syndrome or its specific components in China. Materials and methods: Data were taken from the 2011 and 2015 waves of China Health and Retirement Longitudinal Study (CHARLS). Habitual sleep duration (≤6, 6∼8 [reference], >8 h), daytime napping (0, 1∼60 [reference], and >60 min) were determined by self-reported questionnaires. Metabolic syndrome was defined by blood assessment and biomarkers combined with self-reported doctors' diagnosis. Incident stroke was determined by reported stroke from 2011 to 2015 wave. Cross-sectional and longitudinal associations between sleep and (incident) stroke at baseline and 4-year follow-up period were tested among the population with metabolic syndrome and its components. Results: A U-shaped relationship was observed between sleep duration and stroke in cross-sectional analysis. Sleep ≤ 6 h/night had a greater risk of incident stroke (hazard ratio [HR] 1.65; 95% confidence interval [CI] 1.04-2.61) compared with sleep 6∼8 h/night. And the HR of stroke was 1.62 (95%CI, 1.03-2.53) for sleep < 7 h/day compared to 7∼9 h/day. These associations were more evident in the female and individuals aged 45-65 years. Furthermore, the effect of short sleep duration on incident stroke was different in each component of metabolic syndrome, which was more pronounced in participants with elevated blood pressure. And a significant joint effect of sleeping ≤ 6 h/night and no napping on risk of stroke was observed (HR 1.82, 95%CI 1.06-3.12). Conclusion: Short sleep duration was an independent risk factor for incident stroke, especially among females, individuals aged 45-65 years, or those with some components of metabolic syndrome, such as hypertension. Napping could buffer the risk of short sleep duration on incident stroke.

Serum copper decrease and cerebellar atrophy in patients with nitrous oxide-induced subacute combined degeneration: two cases report.

BACKGROUND: Subacute combined degeneration (SCD) is a neurological complication commonly associated with vitamin B12 deficiency. It can result from nitrous oxide (N2O) abuse and cause neuropsychiatric symptoms. However, there has been no literature regarding alterations of serum copper and cerebellum in SCD patients. CASE PRESENTATION: We reported two cases of young SCD patients with histories of N2O abuse. In these cases, elevated homocysteine, macrocytic anemia, spinal cord abnormalities, and peripheral nerve injuries were detected. In addition, decreased serum copper level and cerebellar atrophy were reported for the first time. The patients' symptoms improved after withdrawal of N2O exposure and vitamin B12 supplements. CONCLUSION: We reported two SCD cases with serum copper alteration and cerebellar atrophy after N2O abuse for the first time. These might be crucial complements to the diagnosis of SCD.

Cerebral Small-Vessel Disease and Risk of Incidence of Depression: A Meta-Analysis of Longitudinal Cohort Studies.

Background Results of several longitudinal cohort studies suggested an association between cerebral small-vessel disease and depression. Therefore, we performed a meta-analysis to explore whether cerebral small-vessel disease imparts increased risk for incident depression. Methods and Results We searched prospective cohort studies relevant to the relationship between cerebral small-vessel disease and incident depression published through September 6, 2019, which yielded 16 cohort studies for meta-analysis based on the relative odds ratio (OR) calculated with fixed- and random-effect models. Baseline white matter hyperintensities (WMHs) (pooled OR, 1.37; 95% CI, 1.14-1.65), enlarged perivascular spaces (pooled OR, 1.33; 95% CI, 1.03-1.71), and cerebral atrophy (pooled OR, 2.83; 95% CI, 1.54-5.23) were significant risk factors for incident depression. Presence of deep WMHs (pooled OR, 1.47; 95% CI, 1.05-2.06) was a stronger predictor of depression than were periventricular WMHs (pooled OR, 1.31; 95% CI, 0.93-1.86). What's more, the pooled OR increased from 1.20 for the second quartile to 1.96 for the fourth quartile, indicating that higher the WMH severity brings greater risk of incident depression (25th-50th: pooled OR, 1.20; 95% CI, 0.68-2.12; 50th-75th; pooled OR, 1.42; 95% CI, 0.81-2.46; 75th-100th: OR, 1.96; 95% CI, 1.06-3.64). These results were stable to subgroup analysis for age, source of participants, follow-up time, and methods for assessing WMHs and depression. Conclusions Cerebral small-vessel disease features such as WMHs, enlarged perivascular spaces, and cerebral atrophy, especially the severity of WMHs and deep WMHs, are risk factors for incident depression.

Coronavirus Disease 2019 (COVID-2019) Infection Among Health Care Workers and Implications for Prevention Measures in a Tertiary Hospital in Wuhan, China.

Importance: Health care workers (HCWs) have high infection risk owing to treating patients with coronavirus disease 2019 (COVID-19). However, research on their infection risk and clinical characteristics is limited. Objectives: To explore infection risk and clinical characteristics of HCWs with COVID-19 and to discuss possible prevention measures. Design, Setting, and Participants: This single-center case series included 9684 HCWs in Tongji Hospital, Wuhan, China. Data were collected from January 1 to February 9, 2020. Exposures: Confirmed COVID-19. Main Outcomes and Measures: Exposure, epidemiological, and demographic information was collected by a structured questionnaire. Clinical, laboratory, and radiologic information was collected from electronic medical records. A total of 335 medical staff were randomly sampled to estimate the prevalence of subclinical infection among a high-risk, asymptomatic population. Samples from surfaces in health care settings were also collected. Results: Overall, 110 of 9684 HCWs in Tongji Hospital tested positive for COVID-19, with an infection rate of 1.1%. Of them, 70 (71.8%) were women, and they had a median (interquartile range) age of 36.5 (30.0-47.0) years. Seventeen (15.5%) worked in fever clinics or wards, indicating an infection rate of 0.5% (17 of 3110) among first-line HCWs. A total of 93 of 6574 non-first-line HCWs (1.4%) were infected. Non-first-line nurses younger than 45 years were more likely to be infected compared with first-line physicians aged 45 years or older (incident rate ratio, 16.1; 95% CI, 7.1-36.3; P < .001). The prevalence of subclinical infection was 0.74% (1 of 135) among asymptomatic first-line HCWs and 1.0% (2 of 200) among non-first-line HCWs. No environmental surfaces tested positive. Overall, 93 of 110 HCWs (84.5%) with COVID-19 had nonsevere disease, while 1 (0.9%) died. The 5 most common symptoms were fever (67 [60.9%]), myalgia or fatigue (66 [60.0%]), cough (62 [56.4%]), sore throat (55 [50.0%]), and muscle ache (50 [45.5%]). Contact with indexed patients (65 [59.1%]) and colleagues with infection (12 [10.9%]) as well as community-acquired infection (14 [12.7%]) were the main routes of exposure for HCWs. Conclusions and Relevance: In this case series, most infections among HCWs occurred during the early stage of disease outbreak. That non-first-line HCWs had a higher infection rate than first-line HCWs differed from observation of previous viral disease epidemics. Rapid identification of staff with potential infection and routine screening among asymptomatic staff could help protect HCWs.

Neutrophil to high-density lipoprotein ratio has a superior prognostic value in elderly patients with acute myocardial infarction: a comparison study.

BACKGROUND: The importance of the lipid-related biomarkers has been implicated in the pathological process and prognosis of acute myocardial infarction (AMI). Our work was conducted to discuss and compare the predictive ability of the neutrophil to high-density lipoprotein cholesterol (HDL-C) ratio (NHR) with other existing prognostic indices, for instance, the monocyte to HDL-C ratio (MHR) and the low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (LDL-C/HDL-C) in elderly patients with AMI. METHODS: Our population was 528 consecutive elderly AMI patients (65-85 years) who were enrolled from Tongji Hospital and grouped according to the cutoff points which were depicted by the receiver operating characteristic (ROC). The Kaplan-Meier curves were plotted with the survival data from the follow-up to investigate the difference between cutoff point-determined groups. Moreover, we assessed the impact of NHR, MHR, LDL-C/HDL-C on the long-term mortality and recurrent myocardial infarction (RMI) with Cox proportional hazard models. RESULTS: Mean duration of follow-up was 673.85 ± 14.32 days (median 679.50 days). According to ROC curve analysis, NHR ≥ 5.74, MHR ≥ 0.67, LDL-C/HDL-C ≥ 3.57 were regarded as high-risk groups. Kaplan-Meier analysis resulted that the high-NHR, high-MHR and high-LDL-C/HDL-C groups presented higher mortality and RMI rate than the corresponding low-risk groups in predicting the long-term clinical outcomes (log-rank test: all P < 0.050). In multivariate analysis, compared with MHR and LDL-C/HDL-C, only NHR was still recognized as a latent predictor for long-term mortality (harzard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.02 to 3.75, P = 0.044) and long-term RMI (HR: 2.23, 95% CI: 1.04 to 4.79, P = 0.040). Furthermore, the positive correlation between NHR and Gensini score (r = 0.15, P < 0.001) indicated that NHR was relevant to the severity of coronary artery to some extent. CONCLUSIONS: NHR, a novel laboratory marker, might be a predictor of the long-term clinical outcomes of elderly patients with AMI, which was superior to MHR and LDL-C/HDL-C.

Could platelet-to-lymphocyte ratio be a predictor for contrast-induced nephropathy in patients with acute coronary syndrome?: A systematic review and meta-analysis.

BACKGROUND: Contrast-induced nephropathy (CIN) is acute renal failure observed after administration of iodinated contrast media during angiographic or other medical procedures. In recent years, many studies have focused on biomarkers that recognize CIN and/or predict its development in advance. One of the many biomarkers studied is the platelet-to-lymphocyte ratio (PLR). We performed a systematic review and meta-analysis to evaluate the correlation between PLR level and CIN. METHODS: Relevant studies were searched in PUBMED, EMBASE, and Web of Science until September 15, 2018. Case-control studies reporting admission PLR levels in CIN and non-CIN group in patients with acute coronary syndrome (ACS) were included. The pooled weighted mean difference (WMD) and 95% confidence intervals (95%CI) were calculated to assess the association between PLR level and CIN using a random-effect model. RESULTS: Six relevant studies involving a total of 10452 ACS patients (9720 non-CIN controls and 732 CIN patients) met our inclusion criteria. A meta-analysis of 6 case-control studies showed that PLR levels were significantly higher in CIN group than those in non-CIN group (WMD = 33.343, 95%CI = 18.863 to 47.823, P < .001, I = 88.0%). CONCLUSION: For patients with ACS after contrast administration, our meta-analysis shows that on-admission PLR levels in CIN group are significantly higher than those of non-CIN group. However, large and matched cohort studies are needed to validate these findings and assess whether there is a real connection or just an association.

Association between fetuin-A and prognosis of CAD: A systematic review and meta-analysis.

BACKGROUND: Fetuin-A is an anti-inflammation and anti-calcification factor involved in the course of coronary artery disease (CAD). But the association between serum fetuin-A level and the prognosis of CAD patients was still controversial. To clarify the association between serum fetuin-A level and the prognosis of CAD patients, we conducted the present meta-analysis. METHODS: The included studies should be potentially relevant prospective studies published in English language before January 2019. The target population of the present meta-analysis was restricted to patients with CAD. The results of studies must report hazard ratio (HR) or Kaplan-Meier survival curve for all-cause mortality or incidence of secondary cardiovascular disease (CVD) events. The pooled HRs were analysed by the method of meta-analysis. RESULTS: A total of four prospective studies, including 4256 participants with CAD disease, were chosen to be included. The pooled HR for all-cause mortality was 0.57 (95% CI: 0.37-0.87), showing a statistically significant association between high serum fetuin-A level and low all-cause mortality in CAD patients. For the incidence of secondary CVD events, the pooled HR was 0.86 (95% CI: 0.60-1.23), indicating no statistically significant association between serum fetuin-A level and incidence of secondary CVD events in CAD patients. CONCLUSION: High serum fetuin-A level associated with lower all-cause mortality in patients with CAD. No association between serum fetuin-A level and incidence of secondary CVD events was found in patients with CAD.