Identification of Hub Genes Associated with Immune Infiltration in Cardioembolic Stroke by Whole Blood Transcriptome Analysis

Cardioembolic stroke (CS) is the most common type of ischemic stroke in the clinic, leading to high morbidity and mortality worldwide. Although many studies have been conducted, the molecular mechanism underlying CS has not been fully grasped. This study was aimed at exploring the molecular mechanism of CS using comprehensive bioinformatics analysis and providing new insights into the pathophysiology of CS. We downloaded the public datasets GSE58294 and GSE16561. Differentially expressed genes (DEGs) were screened via the limma package using R software. CIBERSORT was used to estimate the proportions of 22 immune cells based on the gene expression profiling of CS patients. Using weighted gene correlation network analysis (WGCNA) to cluster the genes into different modules and detect relationships between modules and immune cell types, hub genes were identified based on the intersection of the protein-protein interaction (PPI) network analysis and WGCNA, and their clinical significance was then verified using another independent dataset GSE16561. Totally, 319 genes were identified as DEGs and 5413 genes were clustered into nine modules using WGCNA. The blue module, with the highest correlation coefficient, was identified as the key module associated with stroke, neutrophils, and B cells naïve. Based on the PPI analysis and WGCNA, five genes (MCEMP1, CLEC4D, GPR97, TSPAN14, and FPR2) were identified as hub genes. Correlation analysis indicated that hub genes had general association with infiltration-related immune cells. ROC analysis also showed they had potential clinical significance. The results were verified using another dataset, which were consistent with our analysis. Five crucial genes determined using integrative bioinformatics analysis might play significant roles in the pathophysiological mechanism in CS and be potential targets for pharmaceutic therapies.

Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection

Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.

Neonatal pulmonary hypertension after severe early-onset fetal growth restriction: post hoc reflections on the Dutch STRIDER study

The aim was to reflect on the unexpected finding of persistent pulmonary hypertension of the neonate (PPHN) and pulmonary hypertension in infants born within the Dutch STRIDER trial, its definition and possible pathophysiological mechanisms. The trial randomly assigned pregnant women with severe early-onset fetal growth restriction to sildenafil 25 mg three times a day versus placebo. Sildenafil use did not reduce perinatal mortality and morbidity, but did result in a higher rate of neonatal pulmonary hypertension (PH). The current paper reflects on the used definition, prevalence, and possible pathophysiology of the data on pulmonary hypertension. Twenty infants were diagnosed with pulmonary hypertension (12% of 163 live born infants). Of these, 16 infants had PPHN shortly after birth, and four had pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia. Four infants with PPHN in the early neonatal period subsequently developed pulmonary hypertension associated with bronchopulmonary dysplasia in later life. Infants with pulmonary hypertension were at lower gestational age at delivery, had a lower birth weight and a higher rate of neonatal co-morbidity. The infants in the sildenafil group showed a significant increase in pulmonary hypertension compared to the placebo group (relative risk 3.67; 95% confidence interval 1.28 to 10.51, P = 0.02).Conclusion: Pulmonary hypertension occurred more frequent among infants of mothers allocated to antenatal sildenafil compared with placebo. A possible pathophysiological mechanism could be a “rebound” vasoconstriction after cessation of sildenafil. Additional studies and data are necessary to understand the mechanism of action. What is Known:• In the Dutch STRIDER trial, persistent pulmonary hypertension in the neonate (PPHN) was more frequent among infants after antenatal sildenafil exposure versus placebo. What is New:• The current analysis focuses on the distinction between PPHN and pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia and on timing of diagnosis and aims to identify the infants at risk for developing pulmonary hypertension.• The diagnosis pulmonary hypertension is complex, especially in infants born after severe early-onset fetal growth restriction. The research field could benefit from an unambiguous consensus definition and standardized screening in infants at risk is proposed.

Prenatal stress programs behavioral pattern separation in adult mice

Stress is an unavoidable condition in human life. Stressful events experienced during development, including in utero, have been suggested as one major pathophysiological mechanism for developing vulnerability towards neuropsychiatric and neurodevelopmental disorders in adulthood. One cardinal feature of such disorders is impaired cognitive ability, which may in part rely on abnormal structure and function of the hippocampus. In the hippocampus, the dentate gyrus is a site of continuous neurogenesis, a process that has been recently implicated in spatial pattern separation, a cognitive phenomenon that serves to reduce the degree of overlap in the incoming information to facilitate its storage with minimal interference. We previously reported that adult neurogenesis is altered by prenatal stress allowing us to hypothesize that prenatal stress may possibly lead to impairment in pattern separation. To test this hypothesis, both control (C) and prenatally stressed (PS) adult mice were tested for metric and contextual discrimination abilities. We report for the first time that prenatal stress impairs pattern separation process, a deficit that may underlie their cognitive alterations and that may result in defective behaviors reminiscent of psychiatric illness such as post-traumatic stress disorder.

Mechanism of Depression through Brain Function Imaging of Depression Patients and Normal People

In recent years, functional magnetic resonance technology has discovered that abnormal connections in different brain regions of the brain may serve as the pathophysiological mechanism of mental illness. Exploring the mechanism of information flow and integration between different brain regions is of great significance for understanding the pathophysiological mechanism of mental illness. This article aims to analyze the mechanism of depression by comparing human brain images of normal people and patients with depression and conduct research. Fluoxetine, a selective 5-HT reuptake inhibitor (SSRI) widely used in clinical practice, can selectively inhibit 5-HT transporter and block the reuptake of 5-HT by the presynaptic membrane. The effect of 5-HT is prolonged and increased, thereby producing antidepressant effects. It has low affinity for adrenergic, histaminergic, and cholinergic receptors and has a weaker effect, resulting in fewer adverse reactions. This paper uses the comparative experiment method and the Welch method and uses the average shortest path length L to describe the average value of the shortest path length between two nodes in the network. Attention refers to the ability of a person’s mental activity to point and to concentrate on something. Sustained attention means that attention is kept on a certain cognitive object or activity for a certain period of time, which is also called the stability of attention. The research on attention of depression patients generally focuses on continuous attention, and the results obtained show inconsistencies. Most studies have shown that the sustained attention of the depression group is significantly worse than that of the healthy control group. An overview of magnetic resonance imaging technology and an analysis of depression based on resting state were carried out. The key brain areas of the sample core network were scanned, and the ALFF results were analyzed. The data showed that the severity of depression in the depression group was negatively correlated with the ReHo value in the posterior left cerebellum ( P = 0.010 ). The sense of despair was negatively correlated with the ReHo value in the posterior right cerebellum ( P = 0.013 ). The diurnal variation was negatively correlated with the ReHo value of the left ring ( P = 0.014 ). It was positively correlated with the ReHo value of the left ventricle ( P = 0.048 ). This experiment has better completed the research on the mechanism of depression by analyzing the functional images of patients with depression and normal human brain.

Midbrain injury in patients with subarachnoid hemorrhage: a diffusion tensor imaging study

We investigated the characteristics of midbrain injuries in patients with spontaneous subarachnoid hemorrhage (SAH) by using diffusion tensor imaging (DTI). Twenty-seven patients with SAH and 25 healthy control subjects were recruited for this study. Fractional anisotropy (FA) and mean diffusivity (MD) data were obtained for four regions of the midbrain (the anterior ventral midbrain, posterior ventral midbrain, tegmentum area, and tectum) in 27 hemispheres that did not show any pathology other than SAH. The mean FA and MD values of the four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) of the patient group were significantly lower and higher than those of the control group, respectively (p < 0.05). The mean FA values of the patient group were significantly different among the anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum regions (ANOVA; F = 3.22, p < 0.05). Post hoc testing showed that the mean FA value of the anterior ventral midbrain was significantly lower than those of the posterior ventral midbrain, tegmentum, and tectum (p < 0.05); in contrast, there were no differences in mean FA values of the posterior ventral midbrain, tegmentum, and tectum (p > 0.05). However, differences were not observed among four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) in the mean MD values. We detected evidence of neural injury in all four regions of the midbrain of patients with SAH, and the anterior ventral midbrain was the most severely injured among four regions of the midbrain. Our results suggest that a pathophysiological mechanism of these neural injuries might be related to the occurrence of a subarachnoid hematoma.

Novel urinary markers: taurine, dopamine and L-fucose levels in predicting neonatal seizures

Introduction and Aim: Neonatal seizure is an age specific neurological emergency. Their unique pathophysiological mechanism has become subject of interest for many research studies. The recurrence risk for seizures is high during neonatal period and currently used treatment strategies have limited efficacy in preventing it. From past decades although the treatment has not changed, there is a gradual progress in various mechanisms that are involved in generation of seizures and their response to anti-epileptics. With the emergence of new biochemical parameters for risk assessment in patients with seizures, there is a strong need for their comparative evaluation in order to evaluate their potential clinical application. So, this study was carried out to compare the urine levels of taurine, dopamine and fucose in assessing their role in mechanism of seizure. Materials and Methods: After obtaining ethical approval and consent from parents total 43 neonates, urine taurine, dopamine and fucose were measured in 24 cases of seizures and 19 apparently healthy normal controls. Dopamine and Taurine were measured using ELISA and L-fucose by Dische and Shettles method. Results: The median level of urine fucose was significantly higher in male neonates, taurine was significantly decreased in cases compared to that of controls. Males had higher preponderance to develop seizures. The median levels of urine dopamine were high in cases compared to controls but has not showed any significance. Conclusion: Amino acid like taurine, carbohydrate moiety like fucose and a neuromodulator like dopamine may have a mechanistic role in development of seizures in neonatal period.

Endothelial Dysfunction: From a Pathophysiological Mechanism to a Potential Therapeutic Target

The endothelium is considered the largest organ of the body, composed of a monolayer of endothelial cells (ECs) lining the interior surface of blood and lymphatic vessels [...]

Primary Orthostatic Tremor in Adolescence

Tremor is an involuntary rhythmic muscle contraction, which causes a regular oscillation of a part of the body. Orthostatic tremor is a rare neurological movement disorder characterized by unsteadiness while standing that is relieved when sitting, walking, or lying down. Neurological examination of primary orthostatic tremor is reported to be normal. The pathophysiological mechanism of this condition is not entirely unknown. Symptoms usually start in the sixth decade. Clonazepam is widely used as a first-line medication in the treatment. A 14-year-old girl patient was admitted due to tremor activated on standing, absent while seated or lying, and improved by walking or leaning. Her brain magnetic resonance imaging and laboratory workup were normal. Tremor completely disappeared with clonazepam in 10 days. I report a case of primary orthostatic tremor in adolescence.