Cortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. ...Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.
Cytotoxic CD8+ T cells contribute to neuronal damage in inflammatory and degenerative CNS disorders, such as multiple sclerosis (MS). The mechanism of cortical damage associated with CD8+ T cells is ...not well understood. We developed in vitro cell culture and ex vivo brain slice co-culture models of brain inflammation to study CD8+ T cell-neuron interactions. To induce inflammation, we applied T cell conditioned media, which contains a variety of cytokines, during CD8+ T cell polyclonal activation. Release of IFNγ and TNFα from co-cultures was verified by ELISA, confirming an inflammatory response. We also visualized the physical interactions between CD8+ T cells and cortical neurons using live-cell confocal imaging. The imaging revealed that T cells reduced their migration velocity and changed their migratory patterns under inflammatory conditions. CD8+ T cells increased their dwell time at neuronal soma and dendrites in response to added cytokines. These changes were seen in both the in vitro and ex vivo models. The results confirm that these in vitro and ex vivo models provide promising platforms for the study of the molecular details of neuron-immune cell interactions under inflammatory conditions, which allow high-resolution live microscopy and are readily amenable to experimental manipulation.
Perform an updated systematic review and meta-analysis to determine the cure rate of tonsillectomy and adenoidectomy (T&A) for pediatric obstructive sleep apnea/hypopnea syndrome (OSAHS).
A ...systematic review was performed to identify English-language studies that evaluate the treatment of pediatric (age < 20 years) OSAHS patients with T&A using polysomnography as a metric of cure. Twenty-three studies fit the inclusion criteria and a meta-analysis was performed to determine the overall success. Meta-analysis was also performed to determine the success in obese and comorbid populations vs cohorts of healthy children.
The meta-analysis included 1079 subjects (mean sample size of 42 patients) with a mean age of 6.5 years. The effect measure was the percentage of pediatric patients with OSAHS who were successfully treated (k = 22 studies) with T&A based on preoperative and postoperative PSG data. Random-effects model estimated the treatment success of T&A was 66.3 percent, when cure was defined per each individual study. When "cure" was defined as an apnea-hypopnea index (AHI) of <1 (k = 9 studies), random-effects model estimate for OSAHS treatment success with T&A was 59.8 percent. Postoperative mean AHI was significantly decreased from preoperative levels.
Contrary to popular belief, meta-analysis of current literature demonstrates that pediatric sleep apnea is often not cured by T&A. Although complete resolution is not achieved in most cases, T&A still offers significant improvements in AHI, making it a valuable first-line treatment for pediatric OSAHS.
Long non-coding RNAs (lncRNAs) are emerging as novel diagnostic markers of prostate cancer (PCa) and new determinants of castration-resistant PCa (CRPC), an aggressive and metastatic form of PCa. In ...addition to androgen receptor (AR) signaling, neuroendocrine differentiation (NED) is associated with CRPC. Recent reports demonstrate that the downregulation of repressor element-1 silencing transcription factor (REST) protein is a key step in NED of PCa cells. Here, we report HOTAIR as a novel REST-repressed lncRNA that is upregulated in NED PCa cells and in CRPC. HOTAIR overexpression is sufficient to induce, whereas knockdown of HOTAIR suppressed NED of PCa cells. Gene ontology (GO) analysis of differentially expressed genes under HOTAIR overexpression and in CRPC versus benign prostatic hyperplasia (BPH) suggests that HOTAIR may participate in PCa progression. Taken together, our results provide the first evidence of lncRNA HOTAIR as a driver for NED of PCa cells.
•LncRNA HOTAIR is a novel target of REST.•HOTAIR is upregulated in CRPC during progression.•HOTAIR is a novel driver for NED of PCa cells.
This study is designed to investigate the effects of obstructive sleep apnea/hypopnea syndrome (OSA) surgery on serum leptin levels and metabolic disturbances, both of which contribute to the risk of ...cardiovascular diseases.
Case series with planned data collection.
Tertiary referral medical center.
A retrospective chart review of 101 consecutive patients with OSA who refused or failed conservative therapy and who then underwent upper airway surgery for OSA treatment was conducted. The personal medical history, anthropometric measurements, subjective symptoms, and objective polysomnographic parameters and fasting morning blood samples for leptin and metabolic biomarkers measurements were collected preoperatively and at a minimum of 3 months postoperatively.
Eighty patients with OSA (69 men and 11 women; mean SD age of 42.2 10.2 years) with complete data were included in the final analysis. At least 3 months after surgery, serum leptin, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels and the mean systolic blood pressure (SBP) (night and morning) significantly decreased. According to the classical definition of surgical success, 40 subjects had successful surgery and were categorized as surgical responders, and the other 40 patients who failed surgery were categorized as surgical nonresponders. Significant reductions in serum leptin, total cholesterol, LDL-C, and triglyceride levels and improvement of mean SBP (morning) occurred in surgical responders but not in nonresponders.
Effective OSA surgery improves serum leptin, lipid profiles, and SBP. Further studies are needed to investigate the role of serial measurements of these biomarkers in monitoring surgical outcome of OSA treatment.
To investigate the incidence rate of postextubation dysphagia (PED) in patients with COVID-19, as well as relative factors potentially influencing the clinical course of dysphagia.
Six databases ...including PubMed, MEDLINE, Embase, ScienceDirect, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched with no restriction on the language.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Data were extracted and cross-examined among 3 of the authors. The random-effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of the PED incidence rate. Subgroup analyses, sensitivity analyses, and metaregression were also performed to identify the heterogeneity among the studies.
A total of 594 patients were enrolled and analyzed from the 10 eligible studies. The weighted incidence of PED in patients with COVID-19 was 66.5% (95% CI: 49.7%-79.9%). Age was the potential factor influencing the incidence rate after heterogeneity was adjusted by the metaregression analysis.
Compared to the current evidence reporting only 41% of the non-COVID patients experienced PED, our study further disclosed that a higher 66.5% of COVID-19 patients suffered from PED, which deserves global physicians' attention. With the association between COVID-19 and dysphagia having been more clearly understood, future clinicians are suggested to identify intubated patients' risk factors earlier to strengthen PED care programs in the era of COVID-19.
Objective: Many patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) are incapable of using continuous positive airway pressure. These patients therefore turn to surgical options as a ...salvage treatment. Early studies and reviews focused on the efficacy of uvulopalatopharyngoplasty, a single‐level procedure for the treatment of OSAHS. Since OSAHS is usually caused by multilevel obstructions, the true focus on efficacy should be on multilevel surgical intervention. The purpose of this paper is to provide an overview of the literature on multilevel surgery for OSAHS patients.
Study Design: Systematic review of the literature and meta‐analysis focusing on subjective and objective outcomes of patients with OSAHS treated with multilevel surgery of the upper airway.
Methods: We searched PubMed, the Cochrane database, and MEDLINE bibliographic databases up to March 31, 2007, for studies dealing with multilevel surgical modification of the upper airway for the treatment of OSAHS. Additional studies were identified from their reference lists. Articles were included only if the surgical intervention involved at least two of the frequently involved anatomic sites: nose, oropharynx, and hypopharynx.
Results: After applying specific inclusion criteria, 49 multilevel surgery articles (58 groups) were identified. There were 1,978 patients included in the study. The mean minimal follow‐up time was 7.3 months (range, 1 to 100 months). A meta‐analysis was performed to redefine the success rate to be consistent with the commonly agreed upon criteria, namely “a reduction in the apnea/ hypopnea index (AHI) of 50% or more and an AHI of less than 20.” “Success” implies an improved condition and is not meant to imply cure. The recalculated success rate was 66.4%. The overall complication rate was 14.6%. The evidence‐base medicine (EBM) level of these 49 studies revealed that only one study was EBM level 1, two papers were EBM level 3, and the other 46 papers were ranked as level 4 evidence.
Conclusions: Multilevel surgery for OSAHS is obviously associated with improved outcomes, although this benefit is supported largely by level 4 evidence. Future research should focus on prospective and controlled studies.
Abstract
Objectives
Minimally invasive, single‐staged multilevel surgery (MISS MLS) could be an optimal treatment for selected patients with obstructive sleep apnea (OSA). We aim to systematically ...review the efficacy of MISS MLS for patients with OSA, as well as the clinical outcomes and possible complications in OSA patients before and after MISS MLS.
Design and setting
Systematic review and meta‐analysis. Six databases were searched, and the PRISMA guideline was followed.
Participants
Patients with OSA receiving MISS MLS.
Main outcome measures
The random‐effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of MISS MLS for OSA. Subgroup analyses and sensitivity analyses were also performed to identify the heterogeneity among the studies.
Results
There were initially 154 articles for identification. Eventually, six studies with a total of 848 OSA patients completely met the inclusion criteria and were further enrolled for analysis. The pooled analysis showed statistically significant lower AHI (apnea/hypopnea index, /hr.; mean difference: −8.931, 95% CI: −11.591 to −6.271, I
2
= 87.4%), ESS (mean difference: −2.947, 95% CI: −4.465 to −1.429, I
2
= 94.9%), and snoring severity with 0‐10 visual analog scale after surgery (mean difference: −4.966, 95% CI: −5.804 to −4.128, I
2
= 96.4%). The success rate was 46% in mild/moderate OSA; however, 18% in severe OSA. There were no major complications occurred.
Conclusions
The acceptable surgical outcomes, esp. in mild/moderate OSA, and rare complications are the major advantages of MISS MLS. The evidence of this study could aid the decision making in selecting suitable treatment programs for OSA patients.
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