γ-Oryzanol from Rice Bran Antagonizes Glutamate-Induced Excitotoxicity in an In Vitro Model of Differentiated HT-22 Cells.

The excessive activation of glutamate in the brain is a factor in the development of vascular dementia. γ-Oryzanol is a natural compound that has been shown to enhance brain function, but more research is needed to determine its potential as a treatment for vascular dementia. This study investigated if γ-oryzanol can delay or improve glutamate neurotoxicity in an in vitro model of differentiated HT-22 cells and explored its neuroprotective mechanisms. The differentiated HT-22 cells were treated with 0.1 mmol/L glutamate for 24 h then given γ-oryzanol at appropriate concentrations or memantine (10 µmol/L) for another 24 h. Glutamate produced reactive oxygen species and depleted glutathione in the cells, which reduced their viability. Mitochondrial dysfunction was also observed, including the inhibition of mitochondrial respiratory chain complex I activity, the collapse of mitochondrial transmembrane potential, and the reduction of intracellular ATP levels in the HT-22 cells. Calcium influx triggered by glutamate subsequently activated type II calcium/calmodulin-dependent protein kinase (CaMKII) in the HT-22 cells. The activation of CaMKII-ASK1-JNK MAP kinase cascade, decreased Bcl-2/Bax ratio, and increased Apaf-1-dependent caspase-9 activation were also observed due to glutamate induction, which were associated with increased DNA fragmentation. These events were attenuated when the cells were treated with γ-oryzanol (0.4 mmol/L) or the N-methyl-D-aspartate receptor antagonist memantine. The results suggest that γ-oryzanol has potent neuroprotective properties against glutamate excitotoxicity in differentiated HT-22 cells. Therefore, γ-oryzanol could be a promising candidate for the development of therapies for glutamate excitotoxicity-associated neurodegenerative diseases, including vascular dementia.

The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma.

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Extracellular vesicles called exosomes are primarily used as mediators of intercellular signal transmission to control tumor metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with exosome generation in chondrosarcoma motility remains undetermined. Our results found that overexpressing visfatin augments the production of exosomes from chondrosarcoma cells. Visfatin-treated chondrosarcoma exosomes educate macrophage polarization towards the M2 but not M1 phenotype. Interestingly, M2 macrophages polarized by exosomes return to chondrosarcoma cells to facilitate cell motility. According to these findings, chondrosarcoma cells emit more exosomes when treated with visfatin. The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma.

Stereotactic radiotherapy outcomes for intraventricular brain tumours in 11 dogs.

Published radiotherapy data for canine intraventricular tumours are limited. In this retrospective, longitudinal study (9/2011-2018), 11 dogs with intraventricular masses were treated with stereotactic radiotherapy (SRT). Pathologic diagnosis was available from surgery or necropsy in 6/11 cases, revealing choroid plexus papilloma (3) or carcinoma (2), and ependymoma (1). The remainder were magnetic resonance imaging (MRI)-diagnosed as suspected choroid tumours or ependymomas. Tumours were located in the third or lateral ventricle (8), fourth ventricle (2), and cerebellopontine angle (1). Surgery was performed in three dogs prior to radiotherapy, and all showed gross residual/recurrent disease at treatment. Dogs received 8 Gray × 3 fractions (7), or 15 Gray × 1 fraction (4). Ten dogs were deceased at analysis, and one was living. The estimated median overall survival time (OS) from first SRT treatment was 16.9 months (515 days, 95% CI 33-1593 days). The survival time for two pathology-diagnosed carcinoma dogs were 24 and 133 days, respectively, and survival time for dogs with moderate to marked ventriculomegaly (4/11) ranged from 24 to 113 days. A total of 10/11 showed clinical improvement per owner or clinician, but two had short-lived benefits and were euthanized within 6 weeks of SRT. Limited conclusions on radiation-specific complications are possible due to the small dataset and limited follow-up imaging. This study provides preliminary evidence that radiotherapy outcomes are variable with intraventricular tumours, and some long-term survivors are noted.

Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation.

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.

FGF4L2 retrogene copy number is associated with intervertebral disc calcification and vertebral geometry in Nova Scotia Duck Tolling Retrievers.

OBJECTIVES: To evaluate the effects of the chondrodystrophy-associated FGF4L2 retrogene on intervertebral disc (IVD) calcification and vertebral geometry. ANIMALS: 22 Nova Scotia Duck Tolling Retrievers (NSDTR) with no FGF4L2 retrogene (n = 7, wild-type dogs), 1 retrogene copy (8, heterozygous dogs), or 2 retrogene copies (7, homozygous dogs). PROCEDURES: Computed tomography (CT) scans of the vertebral column were analyzed using computer-aided design (CAD) software. IVD calcification, vertebral column length, and vertebral geometry of the third cervical (C3), 13th thoracic (T13), and first lumbar (L1) vertebrae were compared. RESULTS: IVD calcification was not found in wild-type dogs. IVD calcification was more frequent in homozygous dogs than heterozygous (P = .008) or wild-type dogs (P < .001) and in heterozygous dogs compared to wild-type dogs (P < .001). Four IVDs were subclinically herniated in 3 dogs (2 homozygous, 1 heterozygous). Calcified IVD had a greater volume and surface area in heterozygous dogs than homozygous dogs. C3 vertebral canal height-to-width ratio was greater in homozygous dogs than heterozygous dogs (P = .044) and wild-type dogs (P = .010). CLINICAL RELEVANCE: IVD calcification and vertebral geometry can be analyzed using CAD software. The presence of 1 or 2 FGF4L2 copies in the absence of the FGF4L1 retrogene has an additive effect on the number of calcified IVD and a minor effect on vertebral geometry in NSDTR dogs. Data support the use of FGF4L2 phenotyping to reduce clinical disease in segregating breeds and to monitor the introduction of wild-type alleles into fixed breed populations.

Horner syndrome as a physiological biomarker of disease in canine cervical myelopathy.

BACKGROUND: Horner syndrome often occurs with cervical myelopathies and might provide insight into the underlying disease and prognosis. OBJECTIVES: To describe the clinical and imaging features of dogs with cervical myelopathy and concurrent Horner syndrome and to determine association of Horner syndrome with diseases or magnetic resonance images (MRI). ANIMALS: Ninety-three client-owned dogs with cervical myelopathy and concurrent Horner syndrome and 99 randomly selected client-owned dogs with cervical myelopathy without Horner syndrome (control cases). METHODS: Retrospective study. Medical records were reviewed to identify Horner and control cases and clinical findings recorded. MRI were reviewed, and lesions characterized and recorded. Descriptive and comparative statistics were performed. RESULTS: Non-compressive disease occurred more frequently in the Horner group compared with controls (58%; 95% CI: 48-68 vs 9%; 95% CI: 5-16; P < .0001). The most common diseases were fibrocartilaginous embolism in the Horner group (44/93; 47%) and intervertebral disc extrusion (76/99; 77%) amongst controls. On MRI, parenchymal hyperintensity was seen more commonly in the Horner group (95%; 95% CI: 88-98) compared with controls (51%; 95% CI: 41-60; P < .0001). In the Horner group, dogs that did not survive to discharge (N = 13) had more extensive MRI lesions relative to the adjacent vertebral length (200%; IQR 110%-575%) compared with survivors (N = 80; 110%; IQR 40%-250%; P = .02). Lateralization of Horner signs and MRI changes matched in 54% of cases. The overall survival rate was high in both Horner (80/93; 86%) and control (95/99; 96%) groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Horner syndrome in cervical myelopathy is commonly associated with noncompressive intraparenchymal disease.

Monoclonal antibody levels and protection from COVID-19

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies in preventing symptomatic SARS-CoV-2 infection. We use data on changes in the in vivo concentration of monoclonal antibodies, and the associated protection from COVID-19, over time to model the dose-response relationship of monoclonal antibodies for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a monoclonal antibody concentration of 54-fold of the in vitro IC50 (95% CI: 16 - 183). This relationship provides a quantitative tool allowing prediction of the prophylactic efficacy and duration of protection for new monoclonal antibodies administered at different doses and against different SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either monoclonal antibody treatment or vaccination. We find no evidence for a difference between the 50% protective titer for monoclonal antibodies and vaccination.

Action of the natural compound gomisin a on Ca2+ movement in human prostate cancer cells.

Gomisin A is a dietary lignan compound isolated from the fruit of Schisandra chinensis and has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative activities. However, the benefit of gomisin A is still not well understood. The action of gomisin A is diverse. However, the effect of gomisin A on Ca2+ signaling in prostate cancer cells is unknown. Ca2+ is a pivotal second envoy that triggers and regulates cellular processes such as apoptosis, fertilization, energy transduction, secretion, and protein activation. The goal of this study was to explore the action of gomisin A on [Ca2+]i and cytotoxicity in PC3 prostate cancer cells. Gomisin A at 100-200 µM provoked [Ca2+]i raises. 20% of the response was reduced by removing external Ca2+. The Ca2+ influx provoked by gomisin A was suppressed by 20% by store-caused Ca2+ entry suppressors: econazole, SKF96365, nifedipine; also by phorbol 12-myristate 13 acetate and GF109203X. Without external Ca2+, gomisin A-caused [Ca2+]i raises were abolished by thapsigargin. In contrast, gomisin A suppressed the [Ca2+]i raises caused by thapsigargin. U73122 fell short to change gomisin A-caused [Ca2+]i responses. Gomisin A (20-100 µM) elicited cytotoxicity in a dose-associated fashion. Blockade of [Ca2+] elevations with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl failed to inhibit cytotoxicity of gomisin A. Collectively, gomisin A evoked [Ca2+]i raises and provoked cytotoxicity in a Ca2+-dissociated fashion in prostate cancer cells.

Determinants of passive antibody effectiveness in SARS-CoV-2 infection

BackgroundA large number of studies have been carried out involving passive antibody administration for the treatment and prophylaxis of COVID-19 and have shown variable efficacy. However, the determinants of treatment effectiveness have not been identified. Here we aimed to aggregate all available data on randomised controlled trials of passive antibody treatment for COVID-19 to understand how the dose and timing affect treatment outcome. MethodsWe analysed published studies of passive antibody treatment from inception to 7 January 2022 that were identified after searching various databases such as MEDLINE, Pubmed, ClinicalTrials.gov. We extracted data on treatment, dose, disease stage at treatment, and effectiveness for different clinical outcomes from these studies. To compare administered antibody levels between different treatments, we used data on in vitro neutralisation of pseudovirus to normalise the administered dose of antibody. We used a mixed-effects regression model to understand the relationship between disease stage at treatment and effectiveness. We used a logistic model to analyse the relationship between administered antibody dose (normalised to the mean convalescent titre) and outcome, and to predict efficacy of antibodies against different Omicron subvariants. FindingsWe found that clinical stage at treatment was highly predictive of the effectiveness of both monoclonal antibodies and convalescent plasma therapy in preventing progression to subsequent stages (p<0.0001 and p=0.0089, respectively, chi-squared test). We also analysed the dose-response curve for passive antibody treatment of ambulant COVID-19 patients to prevent hospitalisation. Using this quantitative dose-response relationship, we predict that a number of existing monoclonal antibody treatment regimens should maintain clinical effectiveness in infection with currently circulating Omicron variants. InterpretationEarly administration of passive antibody therapy is crucial to achieving high efficacy in preventing clinical progression. A dose-response curve was derived for passive antibody therapy administered to ambulant symptomatic subjects to prevent hospitalisation. For many of the monoclonal antibody regimens analysed, the administered doses are estimated to be between 7 and >1000 fold higher than necessary to achieve 90% of the maximal efficacy against the ancestral (Wuhan-like) virus. This suggests that a number of current treatments should maintain high efficacy against Omicron subvariants despite reduction in in vitro neutralisation potency. This work provides a framework for the rational assessment of future passive antibody prophylaxis and treatment strategies for COVID-19. FundingThis work is supported by an Australian government Medical Research Future Fund awards GNT2002073 and MRF2005544 (to MPD, SJK), MRF2005760 (to MPD), an NHMRC program grant GNT1149990 (SJK and MPD), and the Victorian Government (SJK). SJK is supported by a NHMRC fellowship. DC, MPD, ZKM and EMW are supported by NHMRC Investigator grants and ZKM and EMW by an NHMRC Synergy grant (1189490). DSK is supported by a University of New South Wales fellowship. KLC is supported by PhD scholarships from Monash University, the Haematology Society of Australia and New Zealand and the Leukaemia Foundation. TT, HW and CB are members of the National COVID-19 Clinical Evidence Taskforce which is funded by the Australian Government Department of Health. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe identified randomised controlled trials (RCTs) evaluating the effectiveness of SARS-CoV-2-specific neutralising monoclonal antibodies, hyperimmune immunoglobulin and convalescent plasma in the treatment of participants with a confirmed diagnosis of COVID-19 and in uninfected participants with or without potential exposure to SARS-CoV-2. The RCTs were identified from published searches conducted by the Cochrane Haematology living systematic review teams. A total of 37 randomised controlled trials (RCT) of passive antibody administration for COVID-19 were identified. This included 12 trials on monoclonal antibodies, 21 trials of convalescent plasma treatment, and 4 trials of hyperimmune globulin. These trials involved treatment of individuals either prophylactically or at different stages of infection including post-exposure prophylaxis, symptomatic infection, and hospitalisation. The level of antibody administered ranged from a 250 ml volume of convalescent plasma through to 8 grams of monoclonal antibodies. Data for analysis was extracted from the original publications including dose and antibody levels of antibody administered, disease stage and timing of administration, primary outcome of study and whether they reported on our prespecified outcomes of interest, which include protection against symptomatic infection, hospitalisation, need for invasive mechanical ventilation (IMV) and death (all-cause mortality at 30 days). Added value of this studyOur study included data across all 37 RCTs of passive antibody interventions for COVID-19 and aggregated the studies by the stage of infection at initiation of treatment. We found that prophylactic administration or treatment in earlier stages of infection had significantly higher effectiveness than later treatment. We also estimated the dose-response relationship between administered antibody dose and protection from progression from symptomatic ambulant COVID-19 to hospitalisation. We used this relationship to predict the efficacy of different monoclonal antibody treatment regimes against the Omicron subvariants BA.1, BA.2, and BA.4/5. We also used this dose-response relationship to estimate the maximal efficacy of monoclonal antibody therapy in the context of pre-existing endogenous neutralising antibodies. Implications of all the available evidenceThis work identifies that both prophylactic therapy and treatment in the early stages of symptomatic infection can achieve significant protection from infection or hospitalisation respectively. The dose-response relationship provides a quantitative means to predict the change in efficacy of different monoclonal antibodies against new variants and in semi-immune populations based on in vitro neutralisation data. We predict a number of existing monoclonal antibodies will be effective for preventing severe outcomes when administered early in BA.4/5 infections. It is likely that these therapies will provide little protection in individuals with high levels of endogenous neutralising antibodies, such as healthy individuals who have recently received a third dose of an mRNA vaccine.

Effect of track body weight support walking training on lower limb motor function in stroke patients: based on ICF Core Set for Stroke / 中国康复理论与实践

ObjectiveTo evaluate the effect of track body weight support walking training on lower limb motor function in stroke patients using International Classification of Functioning, Disability and Health (ICF) Core Sets for Stroke. MethodsFrom April to October, 2021, 15 stroke patients from Wudang Mountain Hospital received track body weight support walking training everyday for 30 minutes, five times a week for four weeks. Before and after treatment, they were evaluated with Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Berg Balance Scale (BBS), 6-minute Walking Test (6MWT), ICF Core Set for Stroke (gait), and three-dimensional gait analysis. ResultsAfter treatment, the ICF gait function qualifier, FMA-LE score, BBS score, the distance of 6MWT, gait speed, gait symmetry and and the maximum motion angle of hip and knee increased (|t| > 4.141, P < 0.01). ConclusionTrack body weight support walking training could improve the lower limb motor function and gait of stroke patients.

Serum phosphorylated neurofilament heavy chain as a diagnostic biomarker for progressive myelomalacia in dogs with thoracolumbar intervertebral disc herniation.

BACKGROUND: Serum phosphorylated neurofilament-heavy chain (pNF-H) has not been longitudinally evaluated in dogs that develop progressive myelomalacia (PMM) after Type I intervertebral disc herniation (IVDH). OBJECTIVES: To determine if serum pNF-H concentrations would predict outcome of neuroligical disease in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH. ANIMALS: Thirty-nine client-owned dogs with thoracolumbar myelopathy secondary to IVDH. METHODS: Prospective controlled cohort study. Serum was collected from dogs undergoing hemilaminectomy at multiple timepoints. Final neurological status was established at 12 months and groups were stratified accordingly. Comparisons between outcome and pNF-H concentration at each timepoint was examined using Kruskal-Wallis analysis of variance on ranks and receiver operator characteristics curve analysis. RESULTS: Median serum pNF-H concentrations were not significantly different between deep pain negative dogs that did or did not recover at any timepoint (baseline: 0.37 ng/mL [0-0.9 ng/mL] vs 0 ng/mL [0-0.9 ng/mL], P > 1; 24 hours: 1.25 ng/mL [0.35-7.23 ng/mL] vs 1.53 ng/mL [0-11.94 ng/mL], P > 1; 48 hours: 1.22 ng/mL [0.63-6.62 ng/mL] vs 2.12 ng/mL [0-20.72 ng/mL], P > 1; 72 hours: 2.77 ng/mL [1.33-6.62 ng/mL] vs 16.69 ng/mL [4.02-40.12 ng/mL], P > 1). Dogs that developed PMM had significantly higher serum pNF-H concentrations after surgery compared to all other cohorts at 24 hours: 39.88 ng/mL (25.74-50.68 ng/mL); P < .05 and 72 hours: 223.9 ng/mL (155.4-263.7 ng/mL); P < .05. A serum pNF-H concentration ≥31.39 ng/mL was 83.33% sensitive and 100% specific for identifying PMM in this cohort. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum pNF-H is a promising biomarker for antemortem diagnosis of PMM in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH.

Disseminated Rasamsonia argillacea species complex infections in 8 dogs.

BACKGROUND: Clinical features, treatment, and outcome of opportunistic infections with Rasamsonia spp., a nonpigmented filamentous mold, are not well documented in dogs. OBJECTIVES: Describe clinical, radiographic, pathologic features, and outcome of dogs with disseminated Rasamsonia species complex infections. ANIMALS: Eight client-owned dogs. METHODS: Retrospective case series. Medical records were reviewed to describe signalment, history, clinicopathologic and imaging findings, microbiologic and immunologic results, cyto- and histopathologic diagnoses, treatment, and outcome. RESULTS: Presenting complaints were nonspecific with anorexia (n = 5) and back pain (n = 4) most common. Five dogs were German Shepherd dogs. Six dogs had multifocal discospondylitis and 2 had pleural effusion. Six dogs had Rasamsonia piperina and 2 had Rasamsonia argillacea infections with isolates identified using DNA sequencing. Rasamsonia spp. were isolated by urine culture in 5 of 7 dogs. Five of 6 dogs had positive serum Aspergillus galactomannan antigen enzyme immunoassay (EIA) results. Median survival time was 82 days, and 317 days for dogs that survived to discharge. Four died during initial hospitalization (median survival, 6 days). All isolates had low minimum effective concentrations (MECs) to echinocandins with variable minimum inhibitory concentrations (MICs) for azole antifungal drugs. CONCLUSIONS AND CLINICAL IMPORTANCE: Rasamsonia spp. infections in dogs are associated with multisystemic disease involving the vertebral column, central nervous system, kidneys, spleen, lymph nodes, lungs, and heart. The infection shares clinical features with other systemic mold infections and can be misidentified when using phenotypical microbiologic methods. Molecular techniques are required to identify the organism and guide appropriate antifungal treatment.

Glioma-associated microglia/macrophages augment tumorigenicity in canine astrocytoma, a naturally occurring model of human glioma.

BACKGROUND: Glioma-associated microglia/macrophages (GAMs) markedly influence glioma progression. Under the influence of transforming growth factor beta (TGFB), GAMs are polarized toward a tumor-supportive phenotype. However, neither therapeutic targeting of GAM recruitment nor TGFB signaling demonstrated efficacy in glioma patients despite efficacy in preclinical models, underscoring the need for a comprehensive understanding of the TGFB/GAM axis. Spontaneously occurring canine gliomas share many features with human glioma and provide a complementary translational animal model for further study. Given the importance of GAM and TGFB in human glioma, the aims of this study were to further define the GAM-associated molecular profile and the relevance of TGFB signaling in canine glioma that may serve as the basis for future translational studies. METHODS: GAM morphometry, levels of GAM-associated molecules, and the canonical TGFB signaling axis were compared in archived samples of canine astrocytomas versus normal canine brain. Furthermore, the effect of TGFB on the malignant phenotype of canine astrocytoma cells was evaluated. RESULTS: GAMs diffusely infiltrated canine astrocytomas. GAM density was increased in high-grade tumors that correlated with a pro-tumorigenic molecular signature and upregulation of the canonical TGFB signaling axis. Moreover, TGFB1 enhanced the migration of canine astrocytoma cells in vitro. CONCLUSIONS: Canine astrocytomas share a similar GAM-associated immune landscape with human adult glioma. Our data also support a contributing role for TGFB1 signaling in the malignant phenotype of canine astrocytoma. These data further support naturally occurring canine glioma as a valid model for the investigation of GAM-associated therapeutic strategies for human malignant glioma.

Economic evaluation of diagnostic sleep studies for obstructive sleep apnoea: a systematic review protocol.

BACKGROUND: Obstructive sleep apnoea (OSA) is a significant public health problem affecting a large proportion of the population and is associated with adverse health consequences and a substantial economic burden. Despite the existence of effective treatment, undiagnosed OSA remains a challenge. The gold standard diagnostic tool is polysomnography (PSG), yet the test is expensive, labour intensive and time-consuming. Home-based, limited channel sleep study testing (levels 3 and 4) can advance and widen access to diagnostic services. This systematic review aims to summarise available evidence regarding the cost-effectiveness of limited channel tests compared to laboratory and home PSG in diagnosing OSA. METHODS: Eligible studies will be identified using a comprehensive strategy across the following databases from inception onwards: MEDLINE, PsychINFO, SCOPUS, CINAHL, Cochrane Library, Emcare and Web of Science Core Collection and ProQuest databases. The search will include a full economic evaluation (i.e. cost-effectiveness, cost-utility, cost-benefit, cost-consequences and cost-minimisation analysis) that assesses limited channel tests and PSG. Two reviewers will screen, extract data for included studies and critically appraise the articles for bias and quality. Meta-analyses will be conducted if aggregation of outcomes can be performed. Qualitative synthesis using a dominance ranking matrix will be performed for heterogeneous data. DISCUSSION: This systematic review protocol uses a rigorous, reproducible and transparent methodology and eligibility criteria to provide the current evidence relating to the clinical and economic impact of limited channel and full PSG OSA diagnostic tests. Evidence will be examined using standardised tools specific for economic evaluation studies. TRIAL REGISTRATION: PROSPERO (CRD42020150130).

Altered swallowing biomechanics in people with moderate-severe obstructive sleep apnea.

STUDY OBJECTIVES: Dysphagia is a common but under-recognized complication of obstructive sleep apnea (OSA). However, the mechanisms remain poorly described. Accordingly, the aim of this study was to assess swallowing symptoms and use high-resolution pharyngeal manometry to quantify swallowing biomechanics in patients with moderate-severe OSA. METHODS: Nineteen adults (4 female; mean (range) age, 46 ± 26-68 years) with moderate-severe OSA underwent high-resolution pharyngeal manometry testing with 5-, 10-, and 20-mL volumes of thin and extremely thick liquids. Data were compared with 19 age- and sex-matched healthy controls (mean (range) age, 46 ± 27-68 years). Symptomatic dysphagia was assessed using the Sydney Swallow Questionnaire. Swallow metrics were analyzed using the online application swallowgateway.com. General linear mixed model analysis was performed to investigate potential differences between people with moderate-severe OSA and controls. Data presented are means [95% confidence intervals]. RESULTS: Twenty-six percent (5 of 19) of the OSA group but none of the controls reported symptomatic dysphagia (Sydney Swallow Questionnaire > 234). Compared with healthy controls, the OSA group had increased upper esophageal sphincter relaxation pressure (-2 [-1] vs 2 [1] mm Hg, F = 32.1, P < .0001), reduced upper esophageal sphincter opening (6 vs 5 mS, F = 23.6, P < .0001), and increased hypopharyngeal intrabolus pressure (2 [1] vs 7 [1] mm Hg, F = 19.0, P < .05). Additionally, upper pharyngeal pressures were higher, particularly at the velopharynx (88 [12] vs 144 [12] mm Hg⋅cm⋅s, F = 69.6, P < .0001). CONCLUSIONS: High-resolution pharyngeal manometry identified altered swallowing biomechanics in people with moderate-severe OSA, which is consistent with a subclinical presentation. Potential contributing mechanisms include upper esophageal sphincter dysfunction with associated upstream changes of increased hypopharyngeal distension pressure and velopharyngeal contractility. CITATION: Schar MS, Omari TI, Woods CM, et al. Altered swallowing biomechanics in people with moderate-severe obstructive sleep apnea. J Clin Sleep Med. 2021;17(9):1793-1803.

Characteristics of metachronous gastric neoplasms after curative endoscopic submucosal dissection for early gastric neoplasms / 中华医学杂志(英文版)

BACKGROUND@#With the wide application of endoscopic submucosal dissection (ESD) for early gastric neoplasms, metachronous gastric neoplasms (MGN) have gradually become a concern. This study aimed to analyze the characteristics of MGN and evaluate the treatment and follow-up outcomes of MGN patients.@*METHODS@#A total of 814 patients were retrospectively enrolled. All these patients were treated by ESD for early gastric cancer or gastric dysplasia between November 2006 and September 2019 at The First Medical Center of Chinese People's Liberation Army General Hospital. The risk factors for MGN were analyzed using Cox hazard proportional model. Moreover, the cumulative incidence, the correlation of initial lesions and MGN lesions, and the treatment and follow-up outcomes of MGN patients were analyzed.@*RESULTS@#A total of 4.5% (37/814) of patients had MGN after curative ESD. The 3-, 5-, and 7-year cumulative incidences of MGN were 3.5%, 5.1%, and 6.9%, respectively, and ultimately reaching a plateau of 11.3% at 99 months after ESD. There was no significant correlation between initial lesions and MGN lesions in terms of gross type (P = 0.178), location (long axis: P = 0.470; short axis: P = 0.125), and histological type (P = 0.832). Cox multivariable analysis found that initial multiplicity was the only independent risk factor of MGN (hazard ratio: 4.3, 95% confidence interval: 2.0-9.4, P < 0.001). Seventy-three percent of patients with MGN were treated by endoscopic resection. During follow-up, two patients with MGN died of gastric cancer with lymph node metastasis. The disease-specific survival rate was significantly lower in patients with MGN than that in patients without MGN (94.6% vs. 99.6%, P = 0.006).@*CONCLUSIONS@#The MGN rate gradually increased with follow-up time within 99 months after curative gastric ESD. Thus, regular and long-term surveillance endoscopy may be helpful, especially for patients with initial multiple neoplasms.

Gender differences in self-harm and drinking behaviors among high school students in Beijing, China.

BACKGROUND: Self-harm and drinking are both serious problems in adolescents and many studies presented evidence of their association. However, gender differences in this association are seldom deeply discussed. Our study aimed to evaluate the prevalence of self-harm and explore its association with drinking behaviors by gender and investigate the extent to which the gender differences exist in the association between self-harm and drinking. METHODS: A total of 32,362 students in grades 7 to 12 in Beijing, China were anonymously surveyed and included in our study using two-stage, stratified probability proportion sampling. Self-harm, drinking behaviors and other basic information were obtained from an anonymous questionnaire. Demographic variables, self-harm and drinking behaviors were analyzed using the Chi-square test and the Gamma test between genders and the gender differences in this association were analyzed by Log-binomial regression. RESULTS: The total prevalence of self-harm was 13.7% with no significant gender difference (χ2 =0.352, P = 0.553). The prevalence of self-harm in girls decreased with age (G = -0.163, P < 0.001). Self-harm was associated with drinking behaviors in both boys and girls. The Log-binomial regression demonstrated that girls in the 16-19 years old group were at lower risk of self-harm than girls in the 12-15 years old group while this association was weaker in boys (1.493 vs 1.128). The higher OR for self-harm was found among girls with early drinking experiences compared with boys (2.565 vs 1.863). Girls who had previously drunk (i.e. drunk at least once) (2.211 vs 1.636), were currently drinking (3.400 vs 2.122) and performed binge drinking (6.357 vs 3.924) were at greater risk of self-harm than boys. CONCLUSION: Among high school students, self-harm has a significant positive association with drinking and girls with drinking behaviors are at higher risk of suffering self-harm. Identifying adolescents' drinking behaviors is of vital importance to self-harm prevention and special attention should be focused on younger girls.

Oral Treatment of Central Serous Chorioretinopathy Patients Using Propranolol Tablets.

PURPOSE: To evaluate the pharmacological effects of propranolol treatment of patients with central serous chorioretinopathy (CSCR) over 4 months. RESULTS: Among the 89 male and 31 female patients, the mean BCVA decreased to 0.42 ± 0.08 logMAR during CSCR attacks. Oral propranolol showed good effectiveness in reducing CSCR signs after at least 4 months of treatment. The final BCVA of the patients in groups 1 and 2 was 0.09 ± 0.01 and 0.19 ± 0.03 logMAR, respectively (p < 0.05). Moreover, the mean complete remission time in groups 1 and 2 was 1.9 and 3.5 months, respectively (p < 0.05), while the "success" rate in groups 1 and 2 was 95.0% (57/60) and 78.3% (47/60), respectively (p < 0.05). The recurrence rate in groups 1 and 2 was 5.3% (3/57) and 25.5% (12/47) after a further 5 months of follow-up, respectively (p < 0.05). MATERIALS AND METHODS: One hundred and twenty patients were enrolled and randomly divided into two groups that both underwent a visual acuity test and optical coherence tomography (OCT) scanning, between April and December 2017. The 60 patients in group 1 were requested to take propranolol for 4 months, while the other 60 subjects (group 2) received placebo therapy during the same period. The best-corrected visual acuity (BCVA) of every volunteer and an OCT image of each patient were checked and recorded at the beginning of the study and each week thereafter. If the signs of CSCR disappeared completely from the OCT scans, the case was considered a "success" and treatment stopped at once. However, the "success" subjects were further evaluated in follow-ups throughout the next 5 months to determine the rate of recurrence in groups 1 and 2. The time of total complete remission of CSCR from the OCT scans was also measured in groups 1 and 2. CONCLUSION: CSCR patients revealed an excellent prognosis and success rate of 95.0% after taking propranolol. The treatment was able to enhance subretinal fluid (SRF) absorption, shorten the time to total complete remission, and significantly decrease CSCR recurrence. As such, we suggest that taking propranolol may be an alternative and viable choice for CSCR patients, given that the new method was shown to be safe, cheap, effective, well tolerated and convenient.

Diagnosis and clinical outcome following surgical resection of an intracranial grade III anaplastic gemistocytic astrocytoma in a cat.

CASE SUMMARY: A 10-year-old Maine Coon cat was presented for acute onset seizures and cerebrothalamic signs. An intracranial mass, suspected to be a meningioma, was diagnosed on MRI and surgically excised. Histopathology appeared consistent with an atypical meningioma. However, following rapid regrowth of the neoplasm, the patient was humanely euthanized 3 months later. On post-mortem histopathology, the neoplasm was diagnosed as a grade III anaplastic gemistocytic astrocytoma. RELEVANCE AND NOVEL INFORMATION: Gemistocytic astrocytomas are rare brain tumors in the feline patient. This case represents the first report of a feline grade III anaplastic gemistocytic astrocytoma in the cerebrum of a cat with surgical excision and recurrence. The challenging nature of ante-mortem diagnosis and the guarded prognosis, despite surgical intervention, are presented in this report.