AKAP3-mediated type I PKA signaling is required for mouse sperm hyperactivation and fertility†.

The protein kinase A (PKA) signaling pathway, which mediates protein phosphorylation, is important for sperm motility and male fertility. This process relies on A-kinase anchoring proteins that organize PKA and its signalosomes within specific subcellular compartments. Previously, it was found that the absence of A-kinase anchoring protein 3 (AKAP3) leads to multiple morphological abnormalities in mouse sperm. But how AKAP3 regulates sperm motility is yet to be elucidated. AKAP3 has two amphipathic domains, here named dual and RI, in its N-terminus. These domains are responsible for binding regulatory subunits I alpha (RIα) and II alpha (RIIα) of PKA and for RIα only, respectively. Here, we generated mutant mice lacking the dual and RI domains of AKAP3. It was found that the deletion of these domains caused male mouse infertile, accompanied by mild defects in the fibrous sheath of sperm tails. Additionally, the levels of serine/threonine phosphorylation of PKA substrates and tyrosine phosphorylation decreased in the mutant sperm, which exhibited a defect in hyperactivation under capacitation conditions. The protein levels of PKA subunits remained unchanged. But, interestingly, the regulatory subunit RIα was mis-localized from principal piece to midpiece of sperm tail, whereas this was not observed for RIIα. Further protein-protein interaction assays revealed a preference for AKAP3 to bind RIα over RIIα. Collectively, our findings suggest that AKAP3 is important for sperm hyperactivity by regulating type-I PKA signaling pathway mediated protein phosphorylation via its dual and RI domains.

White Matter Hyperintensity is Associated with Malignant Cerebral Edema in Ischemic Stroke Treated with Thrombectomy.

BACKGROUND: White matter hyperintensity (WMH) burden may lead to poor clinical outcomes after endovascular thrombectomy (EVT). But the relationship between WMH burden and cerebral edema (CED) is unclear. PURPOSE: To examine the association between WMH burden and CED and functional outcome in patients treated with EVT. STUDY TYPE: Retrospective. SUBJECT: 344 patients with acute anterior circulation large-vessel occlusion stroke who received EVT at two comprehensive stroke centers. Mean age was 62.6 ± 11.6 years and 100 patients (29.1%) were female. FIELD STRENGTH/SEQUENCE: 3T, including diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) images. ASSESSMENT: The severity of WMH was evaluated using the Fazekas scale on a FLAIR sequence before EVT. The severity of CED was assessed using CED score (three for malignant cerebral edema [MCE]) and net water uptake (NWU)/time on post-EVT cranial CT. The impact of WMH burden on MCE, NWU/time, and 3-month poor outcome (modified Rankin scale >2) after EVT were assessed. STATISTICAL TESTS: Pearson's chi-squared test, Fisher exact test, 2-tailed t test, Mann-Whitney U test, multivariable logistic regression, multivariate regression analysis, Sobel test. A P value <0.05 was considered statistically significant. RESULTS: WMH burden was not significantly associated with MCE and parenchymal hemorrhage (PH) in the whole population (P = 0.072; P = 0.714). WMH burden was significantly associated with an increased risk of MCE (OR, 1.550; 95% CI, 1.128-2.129), higher NWU/time (Coefficient, 0.132; 95% CI, 0.012-0.240), and increased risk of 3-month poor outcome (OR, 1.434; 95% CI, 1.110-1.853) in the subset of patients without PH. Moreover, the connection between WMH burden and poor outcome was partly mediated by CED in patients without PH (regression coefficient changed by 29.8%). DATA CONCLUSION: WMH burden is associated with CED, especially MCE, and poor outcome in acute ischemic stroke patients treated with EVT. The association between WMH burden and poor outcome may partly be attributed to postoperative CED. TECHNICAL EFFICACY: Stage 5.

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid.

OBJECTIVE: This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. METHODS: We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. RESULTS: The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 µg/mL) compared with that before co-administration (88.8 ± 13.6 µg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 µg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). CONCLUSIONS: In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.

Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study.

INTRODUCTION: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. METHODS: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. RESULTS: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. CONCLUSION: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.

Risk factors for cough after pulmonary resection.

BACKGROUND: To investigate the risk factors for cough after pulmonary resection. METHODS: The PubMed, Embase, Web of Science, ClinicalTrials.gov, and China National Knowledge Network databases were searched from inception to November 2022. The Q tests and I2 statistic were used to evaluate the heterogeneity. Odds ratios (OR) were combined using the inverse variance method. All statistical analyses were performed by RevMan 5.4.1. RESULTS: Nineteen studies with 4755 patients were included, the incidence of postoperative cough was 21.1%-55.8%. The results showed that young age [OR = 0.66, 95% CI (0.46, 0.96), p = 0.03], female sex [OR = 1.69, 95% CI (1.07, 2.66), p = 0.02], preoperative cough [OR = 5.96, 95% CI (2.58, 13.73), p < 0.01], right lobe operation [OR = 2.14, 95% CI (1.44, 3.19), p < 0.01], lobectomy [OR = 3.70, 95% CI (1.73, 7.90), p < 0.01], subcarinal lymph node dissection [OR = 3.45, 95% CI (1.86, 6.39), p < 0.01], mediastinal lymph node removal [OR = 3.49, 95% CI (2.07, 5.89), p < 0.01], closure of bronchial stump with stapler [OR = 5.19, 95% CI (1.79, 15.07), p < 0.01], peritracheal lymph node resection [OR = 3.05, 95%CI (1.40,6.64), p < 0.01], postoperative acid reflux [OR = 11.07, 95%CI (4.38,28.02), p < 0.01] were independent risk factors for cough after pulmonary resection. CONCLUSIONS: Young age, female sex, preoperative cough, right lobe operation, lobectomy, subcarinal lymph node dissection, mediastinal lymph node removal, closure of bronchial stump with stapler, peritracheal lymph node resection, and postoperative acid reflux are independent risk factors for cough after pulmonary resection.

Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis.

BACKGROUND: Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0. RESULTS: A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42-2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27-1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients. CONCLUSIONS: In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.

Genetically predicted testosterone and cancers risk in men: a two-sample Mendelian randomization study.

OBJECTIVE: In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. METHODS: We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. RESULTS: Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09-1.26, P = 2.51E-05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48-0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36-0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001-1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. CONCLUSION: This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

Tigecycline-Associated Coagulopathy: A Single-Center Retrospective Analysis.

INTRODUCTION: The purpose of this study was to assess clinical characteristics and risk factors for tigecycline-associated prothrombin time (PT) and activated partial thromboplastin time (aPTT) prolongation. METHODS: We performed a retrospective analysis on coagulation parameters before and during tigecycline treatment in 55 patients in our hospital with severe infections, mainly pneumonia caused by Acinetobacter baumannii. Patients were divided into different groups according to prolongation of PT and aPTT, and clinical features involved were explored. Univariate and multivariable binary logistic regression analyses were used to identify risk factors for tigecycline-associated PT and aPTT increase. RESULTS: We found that PT values increased from 12.73 ± 1.87 to 13.86 ± 2.06 during the treatment compared with premedication (p < 0.001), and the aPTT level prolonged significantly from 33.63 ± 11.24 to 38.15 ± 11.81 (p < 0.001). The multivariate analyses identified 2 variables that were associated with tigecycline-induced PT prolongation: albumin level (p = 0.018) and weight-adjusted tigecycline dosage (p = 0.005). In addition, treatment duration was the only risk factor for tigecycline-induced aPTT prolongation (p = 0.043). CONCLUSION: Albumin level, weight-adjusted tigecycline dosage, treatment duration may serve as risk indicators for tigecycline-associated coagulation dysfunction. Physicians should be careful with coagulation disorder when prescribing tigecycline in clinical practice, especially in patients with risk factors.

Dynamic changes of neutrophil-to-lymphocyte ratio in brain-dead donors and delayed graft function in kidney transplant recipients.

OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) is a simple parameter implying the inflammatory status. We aimed to explore the association of brain-dead donor NLR change with delayed graft function (DGF) in kidney transplant recipients. METHODS: We retrospectively analyzed the data on 102 adult brain-dead donors and their corresponding 199 kidney transplant recipients (2018 - 2021). We calculated ΔNLR by subtracting the NLR before evaluating brain death from the preoperative NLR. Increasing donor NLR was defined as ΔNLR > 0. RESULTS: Forty-four (22%) recipients developed DGF after transplantation. Increasing donor NLR was significantly associated with the development of DGF in recipients (OR 2.8, 95% CI 1.2 - 6.6; p = .018), and remained significant (OR 2.6, 95% CI 1.0 - 6.4; p = .040) after adjustment of confounders including BMI, hypertension, diabetes, and the occurrence of cardiac arrest. When acute kidney injury (AKI) was included in the multivariable analysis, increasing donor NLR lost its independent correlation with DGF, while AKI remained an independent risk factor of recipient DGF (OR 4.5, 95% CI 2.7 - 7.6; p < .001). The area under the curve of combined increasing NLR and AKI in donors (0.873) for predicting DGF was superior to increasing donor NLR (0.625, p = .015) and AKI alone (0.859, p < .001). CONCLUSIONS: Dynamic changes of donor NLR are promising in predicting post-transplant DGF. It will assist clinicians in the early recognition and management of renal graft dysfunction. Validation of this new biomarker in a large study is needed.

Biomarkers of Unfavorable Outcome in Acute Ischemic Stroke Patients with Successful Recanalization by Endovascular Thrombectomy.

BACKGROUND: We aimed to identify plasma markers of unfavorable outcomes for patients with acute ischemic stroke (AIS) after recanalization by endovascular thrombectomy (EVT). METHODS: From November 2017 to May 2019, we prospectively collected 61 AIS patients due to anterior large vessel occlusion who achieved recanalization by EVT. Plasma samples were obtained between 18 and 24 h after recanalization. Unfavorable outcomes included futile recanalization at 90 days and overall early complications within 7 days after EVT. RESULTS: After adjustment for age and initial National Institute of Health Stroke Scale (NIHSS), matrix metalloproteinase-9 (MMP-9), tenascin-C, thioredoxin, ADAMTS13, and gelsolin were independently associated with both futile recanalization and overall early complications significantly (all p < 0.05), while C-reactive protein (CRP) was independently associated with overall early complications (p = 0.031) but at the limit of significance for futile recanalization (p = 0.051). The baseline clinical model (BCM) (including age and initial NIHSS) demonstrated discriminating ability to indicate futile recanalization (area under the curve [AUC] 0.807, 95% confidence interval [CI] 0.693-0.921) and overall early complications (AUC 0.749, 95% CI 0.611-0.887). BCM+MMP-9+thioredoxin enhanced discrimination (AUC 0.908, 95% CI 0.839-0.978, p = 0.043) and reclassification (net reclassification improvement [NRI] 67.2%, p < 0.001) to indicate futile recanalization. With respect to overall early complications, BCM+MMP-9+tenascin-C, BCM+MMP-9+CRP, BCM+MMP-9+ADAMTS13, BCM+tenascin-C+ADAMTS13, and BCM+CRP+ADAMTS13, all improved discrimination (AUC [95% CI]: 0.868 [0.766-0.970], 0.882 [0.773-0.990], 0.886 [0.788-0.984], 0.880 [0.783-0.977], and 0.863 [0.764-0.962], respectively, all p < 0.05 by the DeLong method) and reclassification (NRI 59.1%, 71.8%, 51.1%, 67.4%, and 38.3%, respectively, all p < 0.05). CONCLUSIONS: The increased levels of MMP-9, tenascin-C, CRP, thioredoxin, and decreased levels of ADAMTS13 and gelsolin were independent predictors of futile recanalization in AIS patients after recanalization by EVT.

Dynamic cerebral autoregulation is an independent outcome predictor of acute ischemic stroke after endovascular therapy.

BACKGROUND: Endovascular therapy (EVT) is increasingly used to improve cerebral reperfusion after moderate-to-severe acute ischemic stroke (AIS). However, the influence of hemodynamic factors on clinical outcome is still unclear after EVT. Dynamic cerebral autoregulation (dCA) is an important brain reserve mechanism and is impaired after AIS. This study aimed to explore the role of dCA in predicting the outcome of AIS patients after EVT. METHODS: AIS patients with severe stenosis/occlusion of unilateral middle cerebral artery (MCA) or internal carotid and treatment with EVT were enrolled to receive dCA examinations at the 24 h, 72 h and 7th day after stroke onset. Healthy volunteers were also recruited as controls. DCA was recorded from spontaneous fluctuations of blood pressure and MCA flow velocity. Transfer function analysis was used to derive dCA parameters, including phase difference (PD) and coherence in the low-frequency range (0.06-0.12 Hz). The clinical outcome was measured using the modified Rankin Scale (mRS) at 90 days after onset. Multivariate logistic regression was performed to reveal the correlation between dCA and clinical outcomes. The receiver operation characteristics (ROC) curve was performed to determine the cut-off point of PD. RESULTS: A total of 62 AIS patients and 77 healthy controls were included. Compared with controls, dCA were impaired bilaterally till to 7th day after onset in patients, presenting as much lower PD value on the ipsilateral side. During follow-up, we found that PD on the ipsilateral side at 24 h after onset was significantly lower in patients with unfavourable outcome (n = 41) than those with favourable outcome (n = 21), even after adjustment of confounding factors (p = 0.009). ROC curve analysis revealed that PD < 26.93° was an independent predictor of unfavourable-outcome. CONCLUSION: In AIS patients after EVT, dCA was impaired on both sides over the first 7 days. PD on the ipsilateral side at 24 h after onset is an independent unfavourable-outcome predictor for AIS after EVT.

Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial.

BACKGROUND: Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome for patients with acute ischemic stroke (AIS), but many of them still have substantial disability. Glibenclamide (US adopted name, glyburide), a long-acting sulfonylurea, shows promising result in treating AIS from both preclinical and clinical studies. This study investigates the safety and efficacy of glibenclamide combined with rtPA in treating AIS patients. METHODS: This is a prospective, randomized, double-blind, placebo-controlled, multicenter trial with an estimated sample size of 306 cases, starting in January 2018. Patients aged 18 to 74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4 to 25 points and treated with intravenous rtPA within the first 4.5 h of their clinical onsets, are eligible for participation in this study. The target time from the onset of symptoms to receive the study drug is of 10 h. Subjects are randomized 1: 1 to receive glibenclamide or placebo with a loading dose of 1.25 mg, followed by 0.625 mg every 8 h for total 5 days. The primary efficacy endpoint is 90-day good outcome, measured as modified Rankin Scale of 0 to 2. Safety outcomes are all-cause 30-day mortality and early neurological deterioration, with a focus on cardiac- and glucose-related serious adverse events. DISCUSSION: This study will provide valuable information about the safety and efficacy of oral glibenclamide for AIS patients treated with rtPA. This would bring benefits to a large number of patients if the agent is proved to be effective. TRIAL REGISTRATION: The trial was registered on September 14th 2017 at www.clinicaltrials.gov having identifier NCT03284463. Registration was performed before recruitment was initiated.

Glutamic acid decarboxylase antibodies in neurocritical patients: a culprit or a bystander?

BACKGROUND: Glutamic acid decarboxylase (GAD) is an intracellular enzyme, which is widely expressed in central nervous system (CNS), pancreas, and other organs. GAD antibodies (GAD-Abs) are linked to various neurological disorders. However, the significance of GAD-Abs in neurocritical patients is undetermined. MATERIALS AND METHODS: Patients with serologically positive GAD-Abs and requiring neurocritical care were included. The clinical, laboratory, and outcome data were retrospectively collected. RESULTS: We included 9 patients with serologically positive GAD-Abs. Clinical manifestations involved both CNS and peripheral nervous system (PNS). Six (66.7%) patients had other specific autoimmune antibodies. Non-specific autoimmune responses were observed in 8 (88.9%) patients. All patients clinically responded well to immunotherapy. The titers of GAD-Abs decreased in 7 (77.8%) patients but remained unchanged in the other 2 patients. One (11.1%) patient awoke before the negative conversion of GAD-Abs, and 3 (33.3%) patients remained unconscious and/or under mechanical ventilation for several weeks after the vanishing of GAD-Abs. CONCLUSIONS: Most neurocritical patients with serologically positive GAD-Abs had other specific autoimmune antibodies. All patients responded well to immunotherapy, but not parallel to the titers of GAD-Abs. These results indicated that GAD-Abs might be more a bystander than a culprit in neurocritical patients, suggesting that an underlying autoimmune disease should be explored.

Different memory patterns of digits: a functional MRI study.

BACKGROUND: Psychological investigations and functional imaging technology have been used to describe neural correlations of different types of memory with various stimuli. Memory with limited storage capacity and a short retention time can be classified as short-term memory (STM) while long-term memory (LTM) can be life-long without defined capacity. METHODS: To identify brain activation pattern associated with different modes of memory for numerical figures, we detected brain activities from twenty-two healthy subjects when performing three types of memory tasks for numbers, namely STM, LTM and working memory (WM), by using functional magnetic resonance imaging (fMRI) technique. RESULTS: The result revealed variable patterns of activation in different brain regions responding to different types of memory tasks. The activation regions with primary processing and transient maintenance of STM for numerical figures are located in the visual cortex and mainly encoded by visual representations, while LTM was encoded by semantics and mainly recruiting left frontal cortex. We also found that subcortical structures, such as the caudate nucleus and the marginal division of the striatum, plays important roles in working memory. CONCLUSIONS: Activation of different brain regions in these three kinds of memories, indicating that different kinds of memories rely on different neural correlates and mental processes.

Exploratory analysis of oral glibenclamide in acute ischemic stroke.

OBJECTIVES: Intravenous glibenclamide (GBC) exerts neuroprotection in both preclinical and preliminary clinical studies. This study explored the safety and potential efficacy of oral GBC in patients with acute hemispheric infarction. MATERIALS & METHODS: During January 2017 and August 2017, adult volunteers were recruited to receive oral GBC treatment, if they presented with an acute anterior ischemic stroke and a National Institute of Health Stroke Score of ≥8. Controls were those who met the above inclusion criteria and had not been on GBC or other sulfonylureas prior to stroke or after hospitalization. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary endpoint was the score on the modified Rankin Scale (mRS) at 6 months. RESULTS: We included 213 patients in the unmatched cohort (20 in the GBC group and 193 in the control group) and 40 patients (20 in each group) in the matched cohort. In both cohorts, GBC treatment did not increase the risks of early death, hypoglycemia, and early neurological deterioration. Although GBC did not substantially improve 6-month functional outcome that measured in shift analysis of mRS, a slight trend toward less severe disability and death (mRS 5-6) was observed. In the matched cohort, GBC treatment was associated with lighter brain edema, when CED score was used for evaluation. CONCLUSIONS: In this study, oral GBC is safe in treating acute hemispheric infarction and might have potential in preventing brain edema and consequential severe disability and death. An adequately powered and randomized trial is warranted.

Toxicokinetics and toxic effects of a Chinese PFOS alternative F-53B in adult zebrafish.

6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a Chinese PFOS alternative, has recently been identified in river water, sewage sludge, wildlife and humans, causing great concerns about its potential toxic effects. Here, we report the first investigation of the toxicokinetics and oxidative stress of F-53B in adult zebrafish. Adult male and female zebrafish were exposed to 10 and 100 µg/L of F-53B for 7 days followed by a 5-d depuration period to examine bioaccumulation, distribution, and depuration of F-53B in fish. The results showed that F-53B was readily accumulated in fish tissues with log BCF values of 2.36-3.65, but was eliminated slowly (t1/2 = 152.4-358.5 h). F-53B accumulation was greater in males than in females and the concentration in tissues decreased in the following order: gonad ≈ liver ≫ gill ≫ brain in females and liver ≈ gill ≫ gonad ≫ brain in males, showing sex- and tissue- specific accumulation of F-53B in fish. After chronic exposure to F-53B for 28 days, a significant dose-dependent increase in histopathological changes in the liver were mainly manifested by vacuolation. Furthermore, F-53B also significantly reduced the enzyme activity (or content) of most of the measured oxidative stress-related markers (e.g., SOD, CAT and MDA) except for an increase in GSH-Px activity, indicating that oxidative stress was induced in zebrafish after treatment with F-53B. The results of this study provide important information on the toxicokinetics and toxic effects of F-53B, which will contribute to the ecological risk assessments of F-53B released into surface waters.

Glibenclamide Prevents Water Diffusion Abnormality in the Brain After Cardiac Arrest in Rats.

BACKGROUND: Glibenclamide (GBC) improves neurological outcome after cardiac arrest (CA) in rats. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of GBC by using a high-field MRI system. METHODS: Male Sprague-Dawley rats were subjected to 10-min asphyxial CA followed by cardiopulmonary resuscitation (CPR). Diffusion-weighted imaging (DWI) as well as conventional T2-weighted imaging was conducted prior to CA and at 24, 48, and 72 h after resuscitation. Afterward, histological examination was performed. RESULTS: Twelve rats were randomized to receive GBC (n = 6) or vehicle (n = 6) at 15 min after return of spontaneous circulation, while four rats were set as sham control. Rats that underwent CA/CPR and received vehicle exhibited distinct neurological deficit, which was alleviated by GBC treatment. Marked water diffusion abnormality as demonstrated by hyperintense DWI in vulnerable regions of the brain was detected after CA/CPR, with the most prominent hyperintense DWI observed in the hippocampal CA1 region at 72 h. Consistently, histological examination revealed neuronal swelling, dendritic injury, and activation of astrocytes and microglia in the hippocampal CA1 region in vehicle-treated rats. Correlation analysis revealed that the ADC values in the hippocampus were significantly correlated with the histological findings (all p < 0.05). CONCLUSION: These results suggest that the neuroprotective effects of GBC after CA was exerted, as least in part, through prevention of water diffusion abnormality, namely brain edema.

[Povidone-iodine versus the benzethonium chloride wipe for penile skin disinfection before semen collection from sperm donors].

Objective: To study the influence of povidone-iodine (PI) versus that of the benzethonium chloride wipe (BCW) on semen collection and semen quality of sperm donors undergoing penile skin disinfection and provide some evidence for the selection of disinfection methods for semen collection. METHODS: We used PI from August to December 2015 and BCWs from January to July 2016 for penile skin disinfection before semen collection, with two samples from each donor, one collected with and the other without penis skin disinfection (the blank control group). After semen collection, we conducted a questionnaire investigation on the influence of the two disinfection methods on semen collection and compared the semen parameters between the two groups of sperm donors. RESULTS: Totally, 185 sperm donors were included in this study, of whom 63 underwent penile skin disinfection with PI and the other 122 with BCWs before semen collection. Statistically significant differences were found between the PI and BCW groups in the adaptability to the disinfectant and rigid disinfection procedures (P <0.05), but not in the other items of the questionnaire (P >0.05). Compared with the sperm donors of the blank control group, those of the PI group showed statistically significant difference in the percentage of progressively motile sperm (PMS) (ï¼»63.02 ± 3.18ï¼½% vs ï¼»61.45 ± 4.78ï¼½%, P<0.05), but not in the abstinence time (ï¼»4.97 ± 1.79ï¼½ vs ï¼»4.7 ± 0.94ï¼½ d, P >0.05), semen volume (ï¼»4.11 ± 1.54ï¼½ vs ï¼»4.15 ± 1.61ï¼½ ml, P >0.05), sperm concentration (ï¼»110 ± 29.6ï¼½ vs ï¼»107.5 ± 31.79ï¼½ ×106/ml, P >0.05), or total sperm count (ï¼»439.10 ± 170.13ï¼½ vs ï¼»434.02 ± 186.91ï¼½ ×106/ejaculate, P >0.05), while those of the BCW group exhibited no remarkable difference in any of the above parameters (P >0.05). Among the samples with abnormal semen quality, significantly fewer were found with abnormal PMS in the BCW than in the PI group (1.64% ï¼»2/122ï¼½ vs 9.68% ï¼»6/62ï¼½, P <0.05). However, there were no significant differences between the PI and BCW groups in the abnormal semen volume, abnormal sperm concentration, or the rate of semen bacterial contamination (P >0.05). CONCLUSIONS: Before semen collection from donors, penile skin disinfection with povidone-iodine may affect both the semen collection process and the quality of donor sperm, while the benzethonium chloride wipe can reduce the influence on the semen collection process and does not affect the semen parameters.

Development and Validation of a Grading Scale for Primary Pontine Hemorrhage.

BACKGROUND AND PURPOSE: We aimed to develop and validate a grading scale for predicting 30-day mortality and 90-day functional outcome in patients with primary pontine hemorrhage (PPH). METHODS: We retrospectively reviewed records of consecutive patients with first-ever pontine hemorrhage from 3 teaching hospitals between 2005 and 2012. Independent factors associated with 30-day mortality were identified by logistic regression to establish a risk stratification scale, named the new PPH score. For validation of the new PPH score, we prospectively recruited subjects from 10 units between December 2014 and November 2015. The performance of the new PPH score was presented as discrimination and calibration, measured by area under the curve of the receiver operating characteristic and Hosmer-Lemeshow goodness-of-fit, respectively. RESULTS: Data of 171 patients were available for scale development. The new PPH score consisted of 2 independent factors with individual points assigned as follows: Glasgow Coma Scale score 3 to 4 (=2 points), 5 to 7 (=1 point), and 8 to 15 (=0 point); PPH volume >10 mL (=2 points), 5 to 10 mL (=1 point), and <5 mL (=0 point). An independent cohort of 98 patients was applied as an external validation of the new PPH score. Results showed that the new PPH score was discriminative in predicting both 30-day mortality (area under the curve, 0.902) and 90-day good outcome (area under the curve, 0.927). Furthermore, the new PPH score revealed a good calibration (χ2=1.387; P=0.846) in 30-day mortality prediction. CONCLUSIONS: The new PPH score is simple and reliable in predicting short-term and long-term outcome for PPH patients. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn. Unique identifier: ChiCTR-OOC-14005533.

Characterizing cell surface of blooming Microcystis in Lake Taihu, China.

Microcystis occurs as colonies in the natural environment but disaggregates into single cells in laboratory cultures. In order to explore the mechanism of how Microcystis forms colonies, the zeta potentials of Microcystis cells from the laboratory and the field were studied, and the hydrophobicity of Microcystis colonies in different sizes was investigated in Lake Taihu. The incubation experiment indicated that the zeta potentials of Microcystis cells were affected by growth phase and species. The absolute values in exponential phase were lower than those in stationary phase, suggesting that the cells with rapid growth easily formed colonies due to more instability on the cell surface. The values of Microcystis aeruginosa were higher than those of Microcystis flos-aquae, which confirmed that M. aeruginosa prevailed in waters for a longer time and at a larger size compared with M. flos-aquae. In another aspect, the absolute zeta potentials of Microcystis spp. at pH 7.0 decreased from spring to autumn in the field; the values in spring were higher than those in summer, suggesting that a large-sized Microcystis colony would more easily form in summer. Additionally, differences in hydrophobicity exist among Microcystis colonies of various sizes. The surface hydrophobicity of colonies in the <20 µm size class was higher than that of larger colonies. This characteristic allowed small colonies to easily form large colonies to survive better. These results would be helpful to understand the mechanism of the bloom formation, especially the colony formation, in Microcystis.