Parvalbumin neurons in the anterior nucleus of thalamus control absence seizures.

OBJECTIVE: Anterior nucleus of thalamus (ANT) has been widely accepted as a potential therapeutic target for drug-resistant epilepsy. Although increased volume of the ANT was also reported in patients with absence epilepsy, the relationship between the ANT and absence epilepsy has been barely illustrated. METHODS: Using chemogenetics, we evaluated the effect of ANT parvalbumin (PV) neurons on pentylenetetrazole (PTZ)-induced absence seizures in mice. RESULTS: We found that intraperitoneal injection of PTZ (30 mg/kg) can stably induce absence-like seizures characterized by bilaterally synchronous spike-wave discharges (SWDs). Selective activation of PV neurons in the ANT by chemogenetics could aggravate the severity of absence seizures, whereas selective inhibition of that cannot reverse this condition and even promote absence seizures as well. Moreover, chemogenetic inhibition of ANT PV neurons without administration of PTZ was also sufficient to generate SWDs. Analysis of background EEG showed that chemogenetic activation or inhibition of ANT PV neurons could both significantly increase the EEG power of delta oscillation in the frontal cortex, which might mediate the pro-seizure effect of ANT PV neurons. SIGNIFICANCE: Our findings indicated that either activation or inhibition of ANT PV neurons might disturb the intrinsic delta rhythms in the cortex and worsen absence seizures, which highlighted the importance of maintaining the activity of ANT PV neurons in absence seizure.

Effects of Self-Management Intervention Programs Based on the Health Belief Model and Planned Behavior Theory on Self-Management Behavior and Quality of Life in Middle-Aged Stroke Patients.

OBJECTIVES: To study the effect of self-management intervention programs based on the health belief model and planned behavior theory on self-management behavior and quality of life in middle-aged stroke patients. Most of the intervention studies on the self-management of middle-aged stroke patients focus on traditional Chinese medicine nursing and continuous nursing, lacking theoretical support. In particular, there is a lack of interventions based on the integration of two or more theories. METHOD: The middle-aged stroke patients were divided into the control group and the intervention group according to the disease area. A total of 70 patients were included, and 35 patients were included in the control group and the intervention group, respectively. The control group received routine neurological treatment and health education during hospitalization and continued to receive routine health education for 3 months after discharge. On this basis, the intervention group received an intervention program based on an integrated model of health beliefs and planned behavior theory, including 3 health education sessions during hospitalization and 3 months of postdischarge health education. A self-administered stroke general information questionnaire was used to collect basic information on patients' age, gender, and comorbidities. The Stroke Self-Management Behavior Rating Scale and Stroke-Specific Quality-of-Life Scale (SS-QOL) were used to evaluate the management behavior and quality of life of the patients in both groups before and after the intervention. RESULTS: Before the intervention, there was no statistically significant difference between the two groups in terms of self-management score, quality of life total score, and scores of each dimension (P > 0.05). At different periods after the intervention, the total score of self-management, total score of quality of life, and scores of each dimension were significantly higher in both groups than before the intervention (P < 0.05). In particular, the self-management and quality of life scores of the intervention group were higher than those of the control group at 1 and 3 months after the intervention (P < 0.05). CONCLUSION: The self-management intervention scheme based on the integrated model of health belief and planned behavior theory is beneficial to improve the self-management ability and quality of life of stroke patients. It provides basis for clinical nurses to further improve the self-management ability and quality of life of stroke patients. Our findings may also serve as a reference for caregivers in other countries to improve the self-management and quality of life of stroke patients.

The role of orexin in Alzheimer disease: From sleep-wake disturbance to therapeutic target.

Accumulating evidence has shown that sleep disturbance is a common symptom in Alzheimer's disease (AD), which is regarded as a modifiable risk factor for AD. Orexin is a key modulator of the sleep-wake cycle and has been found to be dysregulated in AD patients. The increased orexin in cerebrospinal fluid (CSF) is associated with decreased sleep efficiency and REM sleep, as well as cognitive impairment in AD patients. The orexin system has profuse projections to brain regions that are implicated in arousal and cognition and has been found to participate in the progression of AD pathology. Conversely the orexin receptor antagonists are able to consolidate sleep and reduce AD pathology. Therefore, improved understanding of the mechanisms linking orexin system, sleep disturbance and AD could make orexin receptor antagonists a promising target for the prevention or treatment of AD.

Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a non-inferiority randomized controlled trial.

BACKGROUND: Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients. METHODS: A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg-1·day-1) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o'clock, 11 to 13 o'clock, and 17 to 19 o'clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups. RESULTS: There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3-10.3] vs. 10.7 [9.1-12.1] mmol/L, Z = -2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1-63.7]% vs. 11.8 [3.0-36.7]%, Z = -2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050). CONCLUSIONS: In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03439618; https://clinicaltrials.gov/ct2/show/record/NCT03439618.

Cognitive Effects of Treating Obstructive Sleep Apnea: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cognitive impairment and increased risks of dementia. However, the effect of continuous positive airway pressure (CPAP) on cognitive function in patients with OSA is still controversial. OBJECTIVE: To evaluate the cognitive effects of CPAP treatment on OSA. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials (RCT) in the corresponding fields. RESULTS: Totally 14 studies and 1,926 participants were included in our meta-analysis. Standardized mean difference (SMD) or weighted mean difference (WMD) were calculated for subjective sleepiness and cognitive domains including attention and speed of information processing, executive function, and memory. Individual cognitive scale and subgroup analyses according to OSA severity, length of trial, and RCT design type were further conducted. Significant treatment effect on attention and speed of information processing was only observed in severe OSA patients (SMD, 0.17; 95% CI, 0.02 to 0.31; p = 0.025; I2 = 0%). CONCLUSIONS: Therefore, our meta-analysis indicates that CPAP treatment can partially improve cognitive impairment in the population of severe OSA.

Single nucleotide polymorphism array analysis uncovers a large, novel duplication in Xq13.1 in a floppy infant syndrome patient.

OBJECTIVE: To identify candidate genes for the clinical diagnosis of floppy infant syndrome (FIS) using single nucleotide polymorphism (SNP) array in a specific FIS family. METHODS: SNP array analysis of the whole chromosome copy number was performed in the proband (III1). Multiple polymerase chain reaction (PCR) combined with denaturing high-performance liquid chromatography (DHPLC) was used to validate the array data. RESULTS: A large 5.818182 Mb duplication (Xq13.1: 67987646-73805828), which encompasses 66 known genes, was found in III1. The start and end points of the duplication were confirmed with an SNP array. Duplicated genes with potential roles in central and/or peripheral nervous system development (HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1, and SLC16A2) were confirmed by multiple PCR-DHPLC in III1. The patient's mother and grandmother carry duplications in these eight genes, but only on one X chromosome, while the patient's aunt does not carry any of the duplications. CONCLUSION: Based on the location of the eight candidate genes in Xq13.1, the large duplication found by SNP array does indeed exist and is predicted to be both novel and pathogenic. Moreover, we recommend SNP array as the first option for genetic diagnosis of both large-scale and rare/complicated diseases, such as FIS.

Acute intermittent porphyria presenting with seizures and posterior reversible encephalopathy syndrome: Two case reports and a literature review.

INTRODUCTION: Acute intermittent porphyria (AIP) is a rare and challenging hereditary neurovisceral disease with no specific symptoms. Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome with bilateral reversible posterior gyriform lesions that can be associated with many different conditions, including AIP. Usually, peripheral neuropathy is considered the most common neurological manifestation of AIP. However, AIP should also be considered when seizures and PRES are associated with unexplained abdominal pain. CASE PRESENTATION: Both the patients were presented with seizures and PRES on brain magnetic resonance imaging (MRI). Unexplained abdominal pain occurred before the onset of seizures. The AIP diagnosis was made after repeated Watson-Schwartz tests. Hematin was not available for these 2 patients. However, supportive treatment including adequate nutrition and fluid therapy as well as specific antiepileptic drugs aided the patient's recovery and no acute attacks had occurred by the 3-year follow-up. CONCLUSION: In contrast to other causes of PRES patients, seizure is the most common symptom in AIP patients with PRES. This is a strong diagnostic clue for AIP when ambiguous abdominal pain patients presented with seizures and PRES on brain MRI. A positive prognosis can be achieved with the combination of early recognition, supportive and intravenous hematin therapy, and withdrawal of precipitating factors, including some antiepileptic drugs.

RAGE and its emerging role in the pathogenesis of Parkinson's disease.

Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays crucial roles in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE involves in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy. In CNS, RAGE was primarily expressed in neurons, microglia and vascular endothelial cells. Interacting with ligands, RAGE induces a series of signal transduction cascades and leads to the activation of transcription factor NF-κB as well as increased expression of cytokines like TNF-α, IL-1. Moreover, binding to RAGE can also stimulate the generation of reactive oxygen species (ROS), which is implicated in neuron death. It was reported that RAGE were highly expressed in PD patients when compared to age-matched controls. And RAGE ablation protected nigral dopaminergic neurons against cell death in MPTP treated mice. Here we review this article to elucidate the role of RAGE in PD pathogenesis and highlight the anti-RAGE strategies in the treatment of PD.

Association between TBK1 mutations and risk of amyotrophic lateral sclerosis/frontotemporal dementia spectrum: a meta-analysis.

Recently, mutations in TBK1 (TANK-binding kinase 1) have been reported to be a cause of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) spectrum, but the relationship between them remains unclear owing to the small sample size and low mutation rate. Therefore, we performed a two-stage meta-analysis to investigate the frequency of TBK1 mutations in ALS/FTD patients and the association between the mutations and risk of ALS/FTD spectrum. In the first stage, 12 studies involving 4173 ALS/FTD patients were included. The frequencies of loss of function (LoF) and missense mutations were 1.0% (95% CI 0.6-1.7%) and 1.8% (95% CI 0.9-3.4%) in ALS/FTD patients respectively. Subgroup analysis suggested a higher prevalence of TBK1 mutations in European patients than that in Asian patients. In the second stage, 7 studies involving 3146 cases and 4856 controls were enrolled. Results showed that TBK1 LoF mutations were associated with a significant increased risk for ALS/FTD spectrum (OR 11.78; 95% CI 4.21-33.00; p < 0.0001), while TBK1 missense mutations were associated with a moderately increased susceptibility for ALS/FTD spectrum (OR 1.62; 95% CI 1.19-2.19; p = 0.002). In conclusion, TBK1 LoF and missense mutations are not frequently found in ALS/FTD patients, and both of them are associated with an increased risk for ALS/FTD spectrum.