Dynamic increase in neutrophil levels predicts parenchymal hemorrhage and function outcome of ischemic stroke with r-tPA thrombolysis.

BACKGROUND: The higher level of neutrophil on admission has been reported to predict worse 3-month outcomes in ischemic stroke patients. Our study was to explore the dynamic changes of neutrophil and lymphocyte after r-tPA thrombolysis of ischemic stroke and the relationship with parenchymal hemorrhage (PH) and 3-month function outcome. METHODS: A total of 208 acute ischemic stroke (AIS) patients with intravenous thrombolysis were included and then received 3-month follow-up in the present study. Blood samples for neutrophil and lymphocyte counts were obtained on admission, at 24 h and at 7 days after r-tPA infusion. The associations of increase in neutrophil, lymphocyte, and neutrophil to lymphocyte ratio (NLR) with PH or 3-month poor outcome were examined by logistic regression. RESULTS: Increasing trends in the neutrophil and NLR were observed in AIS patients after r-tPA treatment. Increased level of neutrophil at 24 h after r-tPA infusion but not that on admission was associated with PH (OR = 2.86, P = 0.029) and 3-month poorer functional outcomes (OR = 2.67, P = 0.009). Moreover, patients were divided into four groups according to the percent change in neutrophil within 24 h following r-tPA treatment, and we found that there was a trend of incremental OR when compared higher increase group with lower ones. CONCLUSIONS: Dynamic increase in neutrophil and NLR after stroke may predict PH and 3-month poor outcome in AIS patients receiving r-tPA treatment. Therefore, neutrophil and NLR may serve as activity markers for PH and 3-month poor prognosis in AIS patients with intravenous thrombolysis.

The FGG c.952G>A variant causes congenital dysfibrinogenemia characterized by recurrent cerebral infarction: a case report.

Background: Congenital dysfibrinogenemia (CD) is a rare hereditary coagulation disorder resulting from mutations in fibrinogen genes. CD primarily presents with bleeding symptoms, but it can also lead to thrombotic events, including ischemic stroke. Case presentation: This report describes the case of a 52-year-old Chinese man who was admitted to the hospital twice due to recurrent cerebral infarction, characterized by sudden speech impairment and weakness in the right upper extremity. Brain MRI revealed multiple ischemic changes, predominantly in the left frontal and parietal lobes. Coagulation tests demonstrated reduced plasma fibrinogen (Clauss method), prolonged prothrombin time and thrombin time, and an elevated international normalized ratio. However, the ELISA assay indicated elevated levels of fibrinogen γ-chain protein. Despite a 2-month-old treatment regimen with aspirin, clopidogrel, and atorvastatin after the first hospitalization, the patient experienced a second ischemic stroke. Genetic analysis using whole-exome sequencing (WES) and Sanger sequencing identified a rare heterozygous missense variation, FGG c.952G>A (rs267606810), in both the stroke patient and his asymptomatic sister. Both individuals exhibited the same alterations in fibrinogen, characterized by reduced functional levels but increased antigenic protein. Subsequently, the patient was diagnosed with ischemic stroke associated with congenital dysfibrinogenemia. Conclusion: This case report expands the clinical phenotype spectrum associated with FGG c.952G>A (rs267606810) and underscores the significance of considering CD as a potential etiology for unexplained ischemic stroke, particularly in patients with a family history of coagulation disorders.

Coping with racial discrimination: a preliminary examination of coping strategies in college students at a University in Northeastern U.S.

OBJECTIVE: We examined the associations between coping strategies in response to racism and distress symptoms. SAMPLE: One hundred forty-four racially minoritized students at a northeastern university completed an online survey. METHODS: Participants completed self-report active and emotion-focused coping and distress symptom (i.e., depression and anxiety) measures. Hierarchical regressions were conducted to test: 1) correlations between coping strategies in response to racism and distress symptoms, and 2) whether emotional acceptance moderates the association between active coping in response to racism and distress symptoms. RESULTS: Students' self-compassionate responses to their emotional reactions to discrimination uniquely predicted less distress. In contrast, reports of using resistance and education in response to discrimination were positively correlated with distress symptoms; however, these associations were no longer significant when accounting for emotional acceptance. CONCLUSIONS: Our findings suggest that emotional acceptance coping may be associated with lower distress symptoms. Active coping was associated with increased distress symptoms, except when accounting for emotional acceptance coping.

Ataxia with oculomotor apraxia type 2 caused by a novel homozygous mutation in SETX gene, and literature review.

Objectives: Autosomal recessive inherited ataxia with oculomotor apraxia type 2 (AOA2), caused by SETX gene mutations, is characterized by early-onset, progressive cerebellar ataxia, peripheral neuropathy, oculomotor apraxia and elevated serum α-fetoprotein (AFP). This study aimed to expand and summarize the clinical and genetic characteristics of SETX variants related to AOA2. Methods: The biochemical parameters, electromyogram and radiological findings of the patient were evaluated. Whole-exome sequencing (WES) was performed on the patient using next-generation sequencing (NGS), the variants were confirmed by Sanger sequencing and the pathogenicity of the variants was classified according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. We reviewed 57 studies of AOA2 patients with SETX mutations and collected clinical and genetic information. Results: The patient was a 40-year-old Chinese woman who primarily presented with numbness and weakness of the lower limbs in her teenage years. She had elevated AFP, increased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and decreased anti-Müllerian hormone (AMH) levels. We identified a novel homozygous missense mutation of the SETX gene, c.7118 C>T (p. Thr2373Ile), in the patient via Whole-exome and Sanger sequencing. The variant was located in the DNA/RNA helicase domain and is highly conserved. The protein prediction analysis verified the SETX variant as a damaging alteration and ACMG/AMP guidelines classified it as likely pathogenic. Through a literature review, we identified 229 AOA2 cases with SETX variants, and among the variants, 156 SETX variants were exonic. We found that 107 (46.7%) patients were European, 50 (21.8%) were African and 48 (21.0%) were Asian. Among the Asian patients, five from two families were Mainland Chinese. The main clinical features were cerebellar ataxia (100%), peripheral neuropathy (94.6%), cerebellar atrophy (95.3%) and elevated AFP concentration (92.0%). Most reported SETX mutations in AOA2 patients were missense, frameshift and nonsense mutations. Conclusion: We discovered a novel homozygous variant of the SETX gene as a cause of AOA2 in the current patient and expanded the genotypic spectrum of AOA2. Moreover, the clinical features of AOA2 and genetic findings in SETX were assessed in reported cohorts and are summarized in the present study.

Neutrophil-to-lymphocyte ratio, hyperglycemia, and outcomes in ischemic stroke patients treated with intravenous thrombolysis.

INTRODUCTION: Increased neutrophil-to-lymphocyte ratio (NLR) and hyperglycemia on admission are associated with poor outcomes in acute ischemic stroke (AIS) patients. We sought to evaluate the combined effect of increased NLR and hyperglycemia on the prognosis of ischemia stroke treated with intravenous thrombolysis (IVT). METHODS: Patients with acute ischemic stroke receiving IVT treatment were prospectively enrolled. All participants were followed for 3 months. According to the levels of NLR and blood glucose, patients were categorized into four groups: high NLR or nonhigh NLR with or without hyperglycemia. The associations between NLR values with or without hyperglycemia and outcomes of stroke after thrombolysis were assessed by multivariable logistic regression analysis. RESULTS: Among the 381 stroke patients (median age 68 years, 61.68% man) included, 155 (40.68%) had a poor outcome (modified Rankin Scale score 3-6) during 3 months. After multivariate adjustment, high NLR with hyperglycemia increased the risk of 3-month poor outcome (OR = 4.42; 95% CI, 2.13-9.16), early neurological deterioration (END) (OR = 4.81; 95% CI, 2.08-11.12), and 3-month mortality (OR = 6.56; 95% CI, 1.92-22.40). A significant multiplicative interaction of NLR and blood glucose on 3-month poor outcome in ischemic stroke patients after thrombolysis was observed. CONCLUSIONS: Ischemic stroke patients with concurrent high NLR and hyperglycemia increased risks of END, 3-month poor outcome, and mortality after thrombolysis.

Maternal high fat diet programs hypothalamic-pituitary-adrenal function in adult rat offspring.

Maternal environmental factors such as diet have profound effects on offspring development and later health. The hypothalamic-pituitary-adrenal (HPA) axis is an important stress neuroendocrine system that is subject to programming by early life challenges. The present study was further to investigate whether maternal high fat diet (HFD) exposure during rat pregnancy and lactation can alter the HPA axis activity in adult male offspring. We observed that maternal HFD consumption exerted long-term effects on the basal activity of the HPA axis in adult offspring, with increased mean plasma corticosterone levels that result from elevated steroid pulse frequence and pulse amplitude. More importantly, maternal HFD offspring displayed enhanced corticosterone responses to restraint (1 h) and lipopolysaccharide (25 µg/kg, iv) but not insulin-induced hypoglycemia (0.3U/kg, iv) stress, suggesting a stressor-specific effect of maternal diet on the hyperresponsiveness of the HPA axis to stress. Additionally, maternal HFD exposure markedly attenuated the habituation of HPA responses to repeated restraint stress. These findings demonstrate that perinatal HFD exposure has a potent and long-lasting influence on development of neuroendocrine regulatory mechanisms. Maternal HFD consumption significantly increased basal corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus; nevertheless, similar increments in CRF mRNA levels following restraint were observed between maternal HFD offspring and control rats. Furthermore, the medial and central nuclei of amygdala played a pivotal role in maternal HFD-induced sensitization of the HPA response to psychological and systemic stress, respectively, suggesting that different neural pathways may mediate maternal HFD-induced HPA hyperresponsivity to different types of stressors. Take together, the long-term effects of maternal HFD challenge on the central regulation of the HPA axis, therefore, expose the adult offspring to greater HPA function throughout lifespan, in stressor-specific and region-specific manner.