Study Objectives: The purpose of this study is to conduct a systematic review and meta-analysis evaluating the effects of respiratory muscle therapy (ie, oropharyngeal exercises, speech therapy, breathing exercises, wind musical instruments) compared with control therapy or no treatment in improving apneahypopnea index ([AHI] primary outcome), sleepiness, and other polysomnographic outcomes for patients diagnosed with obstructive sleep apnea (OSA). Methods: Only randomized controlled trials with a placebo therapy or no treatment searched using PubMed, EMBASE, Cochrane, and Web of Science up to November 2018 were included, and assessment of risk of bias was completed using the Cochrane Handbook. Results: Nine studies with 394 adults and children diagnosed with mild to severe OSA were included, all assessed at high risk of bias. Eight of the 9 studies measured AHI and showed a weighted average overall AHI improvement of 39.5% versus baselines after respiratory muscle therapy. Based on our meta-analyses in adult studies, respiratory muscle therapy yielded an improvement in AHI of −7.6 events/h (95% confidence interval [CI] = −11.7 to −3.5; P ≤.001), apnea index of −4.2 events/h (95% CI = −7.7 to −0.8; P ≤ .016), Epworth Sleepiness Scale of −2.5 of 24 (95% CI= −5.1 to −0.1; P ≤ .066), Pittsburgh Sleep Quality Index of −1.3 of 21 (95% CI= −2.4 to −0.2; P ≤ .026), snoring frequency (P = .044) in intervention groups compared with controls. Conclusions: This systematic review highlights respiratory muscle therapy as an adjunct management for OSA but further studies are needed due to limitations including the nature and small number of studies, heterogeneity of the interventions, and high risk of bias with low quality of evidence.
COVID-19 patients show heterogeneity in clinical presentation and outcomes that makes pandemic control and strategy difficult; optimizing management requires a systems biology approach of understanding the disease. Here we sought to potentially understand and infer complex disease progression, immune regulation, and symptoms in patients infected with coronaviruses (35 SARS-CoV and 3 SARS-CoV-2 patients and 57 samples) at two different disease progression stages. Further, we compared coronavirus data with healthy individuals (n = 16) and patients with other infections (n = 144; all publicly available data). We applied inferential statistics (the COVID-engine platform) to RNA profiles (from limited number of samples) derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, a subset of integrated blood-based gene profiles (signatures) distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalization) from recovering-like patients. These signatures also hierarchically represented multiple (at the system level) parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle observations included PBMC-based increases in cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage showed significantly enhanced TNF, IFN-γ, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, our analysis revealed overlapping genes associated with potential comorbidities (associated diabetes) and disease-like conditions (associated with thromboembolism, pneumonia, lung disease, and septicemia). Overall, our COVID-engine inferential statistics platform and study involving PBMC-based RNA profiling may help understand complex and variable system-wide responses displayed by coronavirus-infected patients with further validation.
Temporomandibular joint disorders (TMDs) range from gross anatomic deformities of the disc and hard tissue to functional disturbances. Traditional treatment of TMDs includes physical therapy, use of appliances, pharmacological, surgical and psychological interventions. However, during the late stage of TMDs, conventional management often results in inadequate relief of symptoms. Stem cell-based tissue regeneration has been studied extensively in joint regeneration, including the Temporomandibular Joint (TMJ). This study aims to review the potential of various human stem cells (HSC) for the regeneration of the TMJ. In vitro studies using human mesenchymal stem cells cultured under different conditions to evaluate regeneration of TMJ related structures were searched on PubMed, EMBASE, Cochrane, and Web of Science up to March 2020. In vitro studies utilized several different types of stem cells under varying conditions. Increased osteogenesis and/ or chondrogenesis were noted with stem cell interventions compared to control groups on Alkaline Phosphatase (ALP) activity, Col-I, Col-II, Col-X, RUNX2, LPL, and Aggrecan mRNA expression. This review emphasizes the potential of stem cell therapies in the regeneration of TMJ-related structures. However, further in vivo studies are required to evaluate the efficacy and safety of these therapies in humans. K E Y W O R D S in vitro, mesenchymal stem cells, review, stem cell therapies, temporomandibular disorders, temporomandibular joint 1 | INTRODUCTION The temporomandibular joint (TMJ) is a complex synovial joint with a unique articulation between the temporal glenoid fossa and the mandibular condyle, which are separated by an articular disc composed of avascular and non-innervated dense fibrous connective tissue with a varying amount of fibrocartilage. The articular disc divides the TMJ cavity into upper and lower chambers. Gliding movement occurs in the upper chamber during the maximal mouth opening, while the lower chamber function primarily as a hinge or rotary movement in the early opening. Because the TMJ has a hinge and sliding movable socket, it is classified as ginglymoarthrodial a joint. The TMJ is surrounded by a fibrous connective tissue capsule attached to muscles and tendons. The capsule is lined by a synovium This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Regenerative medicine holds promise to cure radiation-induced salivary hypofunction, a chronic side effect in patients with head and neck cancers, therefore reliable preclinical models for salivary regenerative outcome will promote progress towards therapies. In this study, our objective was to develop a cone beam computed tomography-guided precision ionizing radiation-induced preclinical model of chronic hyposalivation using immunodeficient NSG-SGM3 mice. Using a Schirmer's test based sialagogue-stimulated saliva flow kinetic measurement method, we demonstrated significant differences in hyposalivation specific to age, sex, precision-radiation dose over a chronic (6 months) timeline. NSG-SMG3 mice tolerated doses from 2.5 Gy up to 7.5 Gy. Interestingly, 5–7.5 Gy had similar effects on stimulated-saliva flow (∼50% reduction in young female at 6 months after precision irradiation over sham-treated controls), however, >5 Gy led to chronic alopecia. Different groups demonstrated characteristic saliva fluctuations early on, but after 5 months all groups nearly stabilized stimulated-saliva flow with low-inter-mouse variation within each group. Further characterization revealed precision-radiation-induced glandular shrinkage, hypocellularization, gland-specific loss of functional acinar and glandular cells in all major salivary glands replicating features of human salivary hypofunction. This model will aid investigation of human cell-based salivary regenerative therapies.
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