The reproducibility of clinical OSA subtypes: a population-based longitudinal study

Purpose

The identification of subgroups of obstructive sleep apnea (OSA) is critical to understand disease outcome and treatment response and ultimately develop optimal care strategies customized for each subgroup. In this sense, we aimed to perform a cluster analysis to identify subgroups of individuals with OSA based on clinical parameters in the Epidemiological Sleep Study of São Paulo city (EPISONO). We aimed to analyze whether or not subgroups remain after 8 years, since there is not any evidence showing if these subtypes of clinical presentation of OSA in the same population can change overtime.

Methods

We used data derived from EPISONO cohort, which was followed over 8 years after baseline evaluation. All individuals underwent polysomnography, answered questionnaires, and had their blood collected for biochemical examinations. OSA was defined according to AHI?≥?15 events/h. Cluster analysis was performed using latent class analysis (LCA).

Results

Of the 1042 individuals in the EPISONO cohort, 68% agreed to participate in the follow-up study (n?=?712), and 704 were included in the analysis. We were able to replicate the OSA 3-cluster solution observed in previous studies: disturbed sleep, minimally symptomatic and excessively sleepy in both baseline (36%, 45% and 19%, respectively) and follow-up studies (42%, 43%, and 15%, respectively). The optimal cluster solution for our sample based on Bayesian information criterion (BIC) was 2 cluster for baseline (disturbed sleep and excessively sleepy) and 3 clusters for follow-up (disturbed sleep, minimally symptomatic, and excessively sleepy). A total of 45% of the participants migrated clusters between the two evaluations (and the factor associated with this was a greater delta-AHI (B?=????0.033, df?=?1, p?=?0.003).

Conclusions

The results replicate and confirm previously identified clinical clusters in OSA which remain in the longitudinal analysis, with some percentage of migration between clusters.

     

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R⁺) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D⁺/R⁻). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P < 0.05). During the antiviral prophylaxis, all 20 D⁺/R⁻ KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.     

A High-Fat Diet Increases IL-1, IL-6, and TNF-α Production by Increasing NF-κB and Attenuating PPAR-γ Expression in Bone Marrow Mesenchymal Stem Cells

It is well established that a high-fat diet (HFD) can lead to overweight and ultimately to obesity, as well as promoting low-grade chronic inflammation associated with increased levels of such mediators as TNF-α, IL-1, and IL-6. Bone marrow mesenchymal stem cells (MSCs), which are involved in hematopoietic niches and microenvironments, can be affected by these cytokines, resulting in induction of NF-κB and inhibition of PPAR-γ. Because this phenomenon could ultimately lead to suppression of bone marrow adipogenesis, we set out to investigate the effect of an HFD on the expression of PPAR-γ and NF-κB, as well as the production of IL-1, IL-6, and TNF-α in MSCs. Two-month-old male Wistar rats were fed a HFD diet and evaluated by means of leukograms and myelograms along with blood total cholesterol, triglyceride, and C-reactive protein levels. MSCs were isolated, and PPAR-γ and NF-κB were quantified, as well as IL-1, IL-6, and TNF-α production. Animals that were fed a HFD showed higher levels of blood total cholesterol, triglycerides, and C-reactive protein with leukocytosis and bone marrow hyperplasia. MSCs from HFD animals showed increased production of IL-1, IL-6, and TNF-α and increased NF-κB and reduced PPAR-γ expression. Therefore, ingestion of an HFD induces alterations in MSCs that may influence modulation of hematopoiesis.     

Oligodendrocytes in a dish for the drug discovery pipeline: the risk of oversimplification

正Myelination,remyelination and demyelination: modeling the in vitro drug discovery pipeline: Demyelination is a multifactorial event occurring in diseases primarily involving myelin forming cells(oligodendrocytes, OLs) and their precursors(oligodendrocyte precursor cells, OPCs) such as multiple sclerosis, but is also involved in the pathology of other central nervous system(CNS) injuries and diseases, such as neonatal encephalopathy, brain and spinal     

Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56^–CD16⁺ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.     

Assessment of Hounsfield unit in the differential diagnosis of odontogenic cysts

Objectives:The purpose of this study was to evaluate the usefulness of Hounsfield unit (HU) assessment with multislice-CT in the differentiation of radicular cysts (RCs), dentigerous cysts (DCs) and odontogenic keratocysts (OKCs).Methods:In total, 307 odontogenic cysts (RCs, DCs and OKCs) were included in this study. Cysts with lesion diameter <10 mm, cysts with artefacts affecting measurement of HU values, cysts involving infection and recurrent cysts were regarded as exclusion criteria. Images were acquired in three different types of CT scanners: Aquilion ONE, Discovery CT750 HD and SOMATOM Definition Flash. Differences in HU values among scanners and among types of odontogenic cysts were assessed using one-way analysis of variance; multiple comparisons were performed post hoc, using the Tukey–Kramer honestly significant difference test.Results:In total, 164 cysts were analysed in this study (64 RCs, 57 DCs and 43 OKCs). Regardless of the type of lesion, the Aquilion ONE scanner demonstrated a significant difference in HU value, compared with the Discovery CT750 HD scanner. Regardless of CT scanner model, HU values significantly differed between DCs and OKCs (p < 0.0001), as well as between OKCs and RCs (p < 0.0001).Conclusions:HU values were found to vary among CT scanners and should always be associated with other lesion imaging features while interpreting and elaboration diagnostic hypothesis. Notably, the results suggested that OKCs might be able to be differentiated from DCs and RCs by using HU values.     

Detection of cytokeratins in ghost cells of calcifying cystic odontogenic tumor indicates an altered keratinization and hair follicle differentiation for their development

Calcifying cystic odontogenic tumors (CCOTs) are benign cystic lesions of odontogenic origin characterized by an ameloblastoma-like epithelium and the presence of a group of cells named ghost cells. The pattern of cytokeratin (Ck) expression on these lesions remains unclear and needs to be clarified. To this end, the expression of Ck6, Ck13, Ck14, Ck18, and Ck19 in the epithelium lining of 7 cases of CCOTs was evaluated by immunohistochemistry. For this, the epithelium lining was divided into 3 distinct regions: basal layer, suprabasal layer, and the compartment composed of ghost cells. In this study, 6 cases (85.7%) were classified as type 1 and 1 (14.3%) as type 4. All cases were negative for Ck13 and Ck18, despite the epithelial layer, as well as in the ghost cells. Ck6 was only positive in the ghost cells. Positivity for Ck14 and Ck19 was found in the basal and suprabasal layers, including the ghost cells. The results showing positivity for Ck14 and Ck19 in all of the analyzed cases reinforce CCOT as being of odontogenic origin, and the restricted expression of Ck6 in the ghost cells may be indicative that these cells suffer an altered differentiation into hair follicles in CCOTs.