FBXO6 regulates the anti‐viral immune‐responses via mediating alveolar macrophages survival

alexandrossfakianakis shared this article with you from Inoreader FBXO6 regulates the anti‐viral immune‐responses via mediating alveolar macrophages survival via Journal of Medical Virology Abstract Inducing early apoptosis in alveolar macrophages is one of the strategies influenza A virus (IAV) evolved to subvert host immunity. Correspondingly, the host mitochondrial protein nucleotide-binding oligomerization domain-like receptor (NLR)X1 is reported to interact with virus polymerase basic protein 1-frame 2 (PB1-F2) accessory protein to counteract virus induced apoptosis. Herein, we report that one of the F-box proteins, FBXO6, promotes proteasomal degradation of NLRX1, and thus facilitates IAV-induced alveolar macrophages apoptosis and modulates both macrophage survival and type I interferon (IFN) signaling. We observed that FBXO6-deficient mice infected with IAV exhibited decreased pulmonary viral replication, as well as alleviated inflammatory-associated pulmonary dysfunction and morbidity. Analysis of the lungs of IAV-infected mice revealed markedly reduced leukocyte recruitment but enhanced production of type I IFN in Fbxo6 -/- mice. Furthermore, increased type I IFN production and decreased viral replication were recapitulated in FBXO6 knockdown macrophages and was associated with reduced apoptosis. Through gain- and loss-of-function studies, we found lung resident macrophages but not bone marrow derived macrophages play the key role in the differences FBXO6 signaling pathway brings in the antiviral immune response. In further investigation, we identified that FBXO6 interacted with and promoted the proteasomal degradation of NLRX1. Together, our results demonstrate that FBXO6 negatively regulates immunity against IAV infection by enhancing the degradation of NLRX1 and thus impairs the survival of alveolar macrophages and antiviral immunity of the host. This article is protected by copyright. All rights reserved. View on Web

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Does ACE2 mediate the detrimental effect of exposures related to COVID‐19 risk: A Mendelian randomization investigation

alexandrossfakianakis shared this article with you from Inoreader Does ACE2 mediate the detrimental effect of exposures related to COVID‐19 risk: A Mendelian randomization investigation via Journal of Medical Virology Abstract Objectives Adiposity, smoking and lower socioeconomic position (SEP) increase COVID-19 risk whilst the association of vitamin D, blood pressure, and glycemic traits in COVID-19 risk were less clear. Whether angiotensin-converting enzyme 2 (ACE2), the key receptor for SARS-CoV-2, mediates these associations has not been investigated. We conducted a Mendelian randomization study to assess the role of these exposures in COVID-19 and mediation by ACE2. Methods We extracted genetic variants strongly related to various exposures (vitamin D, blood pressure, glycemic traits, smoking, adiposity and educational attainment (SEP proxy)), and ACE2 cis-variants from genome wide association studies (GWAS, n ranged from 28,204 to 3,037,499) and applied them to GWAS summary statistics of ACE2 (n=28,204) and COVID-19 (severe, hospitalized, and susceptibility, n≤2,942,817). We used inverse variance weighted as the main analyses, with MR-Egger and weighted median as sensitivit y analyses. Mediation analyses were performed based on product of coefficient method. Results Higher adiposity, lifetime smoking index, and lower educational attainment were consistently associated with higher risk of COVID-19 phenotypes whilst there was no strong evidence for an association of other exposures in COVID-19 risk. ACE2 partially mediates the detrimental effects of body mass index (ranged from 4.3% to 8.2%), waist-to-hip ratio (ranged from 11.2% to 16.8%) and lower educational attainment (ranged from 4.0% to 7.5%) in COVID-19 phenotypes whilst ACE2 did not mediate the detrimental effect of smoking. Conclusions We provided genetic evidence that reducing ACE2 could partly lower COVID-19 risk amongst people who were overweight/obese or of lower SEP. This article is protected by copyright. All rights reserved. View on Web

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Imaging of pediatric pancreas tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric pancreas tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer Abstract Primary pancreatic tumors in children are rare with an overall age-adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm, followed by pancreatoblastoma. This paper describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow-up. View on Web

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High-Resolution Single Tooth MRI With an Inductively Coupled Intraoral Coil—Can MRI Compete With CBCT?

alexandrossfakianakis shared this article with you from Inoreader High-Resolution Single Tooth MRI With an Inductively Coupled Intraoral Coil—Can MRI Compete With CBCT? via Investigative Radiology - Current Issue Objectives The aims of this study were to quantify T1/T2-relaxation times of the dental pulp, develop a realistic tooth model, and compare image quality between cone-beam computed tomography (CBCT) and high-resolution magnetic resonance imaging (MRI) of single teeth using a wireless inductively coupled intraoral coil. Methods T1/T2-relaxometry was performed at 3 T in 10 healthy volunteers (283 teeth) to determine relaxation times of healthy dental pulp and develop a realistic tooth model using extracted human teeth. Eight MRI sequences (DESS, CISS, TrueFISP, FLASH, SPACE, TSE, MSVAT-SPACE, and UTE) were optimized for clinically applicable high-resolution imaging of the dental pulp. In model, image quality of all sequences was assessed quantitatively (contrast-to-noise ratio) and qualitatively (visibility of anatomical structures and extent of susceptibility artifacts using a 5-point scoring scale). Cone-beam computed tomography served as the reference modality for qualitative assessment. Statistical analysis was performed using 2-way analysis of variance, Fisher exact test, and Cohen κ. Results In vivo, relaxometry of dental pulps revealed T1/T2 relaxation times at 3 T of 738 ± 100/171 ± 36 milliseconds. For all sequences, an isotropic resolution of (0.21 mm)3 was achieved, with acquisition times ranging from 6:19 to 8:02 minutes. In model, the highest contrast-to-noise ratio values were observed for UTE, followed by TSE and CISS. The best image/artifact quality, however, was found for DESS (mean ± SD: 1.3 ± 0.3/2.2 ± 0.0), FLASH (1.5 ± 0.3/2.4 ± 0.1), and CISS (1.5 ± 0.4/2.5 ± 0.1), at a level comparable to CBCT (1.2 ± 0.3/2.1 ± 0.1). Conclusions Optimized MRI protocols using an intraoral coil at 3 T can achieve an image quality comparable to reference modality CBCT within clinically applicable acquisition times. Overall, DESS revealed the best results, followed by FLASH and CISS. View on Web

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Length of Stay in Patients Undergoing Tracheoplasty: A NSQIP Study

alexandrossfakianakis shared this article with you from Inoreader Length of Stay in Patients Undergoing Tracheoplasty: A NSQIP Study via The Laryngoscope Background Prolonged length of stay (LOS) has been associated with increased morbidity and resource utilization in various surgical procedures. We aim to determine factors associated with increased hospital stay in patient undergoing tracheoplasty. Methods The 2012–2018 National Surgical Quality Improvement Program (NSQIP) database was queried for patients undergoing tracheoplasty. Patient LOS was the primary clinical outcome. A LOS >75th percentile was considered as prolonged and was utilized for bivariate analysis of demographic, comorbidity, and operative characteristics. LOS was utilized as a continuous variable for multivariate linear regression analysis. Results A total of 252 patients were queried. The majority of patients were female (67.5%), white (82.4%), and over the age of 65 (77.0%). Patients had a median LOS of 7 days with the 75th percentile cutoff being defined at 10 days. On bivariate analysis of associated comorbidities, patients with prolonged LOS were more commonly obese (72.4% vs. 53.1%, p = 0.009), diabetic (37.9% vs. 16.5%, p < 0.001), dyspneic (58.6% vs. 40.7%, p = 0.016), and had chronic steroid use (25.9% vs. 12.9%, p = 0.018). Multivariable logistic regression analysis demonstrated significant associations between prolonged LOS and both chronic obstructive pulmonary disorder (COPD) (OR: 3.43, p = 0.020) and chronic steroid use (OR: 3.81, p = 0.018). Conclusions This study elucidates factors associated with prolonged LOS in patients undergoing tracheoplasty. Patients with COPD and chronic steroid use were significantly associated with prolonged LOS. Level of Evidence 4 Laryngoscope, 2022 View on Web

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Phosphatase and tensin homolog determines inflammatory status by differentially regulating the expression of Akt1 and Akt2 in macrophage alternative polarization of periodontitis

alexandrossfakianakis shared this article with you from Inoreader Phosphatase and tensin homolog determines inflammatory status by differentially regulating the expression of Akt1 and Akt2 in macrophage alternative polarization of periodontitis via Journal of Clinical Periodontology Abstract Aims Macrophages are closely involved in periodontitis; however, the molecular mechanism by which macrophages influence periodontitis is not well understood. We investigated the effects of phosphatase and tensin homolog (PTEN) on macrophage polarization, the underlying mechanism, and the regulatory roles in periodontium regeneration. Materials and Methods PTEN expression in periodontitis macrophages was detected ex vivo. The effects of PTEN on macrophage polarization and the underlying mechanisms were investigated in vitro. We also analyzed the ability of PTEN inhibitors to repair periodontitis in vivo, in a ligature-induced mouse model of periodontitis. Results Macrophage PTEN expression in periodontitis patients was significantly higher than that of controls. PTEN inhibition in macrophages induced alternative macrophage polarization, whereas PTEN overexpression facilitated classical polarization. PTEN inhibition facilitated activation of Akt1 while inhibited expression of Akt2. Furthermore, Akt2 overexpression could rescue the effects of PTEN inhibition on NF-κB. Treatment with PTEN inhibitor significantly attenuated the local inflammatory status and prevented alveolar bone resorption in mouse model. Conclusions Our findings suggest that PTEN inhibition could induce alternative macrophage polarization by differentially regulating Akt1 and Akt2. This also changed a pro-inflammatory microenvironment to an anti-inflammatory environment, by subsequently regulating the expression of NF-κB, and thereby attenuated inflammatory alveolar bone resorption induced by ligature. View on Web

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The development and initial validation of self‐report measures of ICD‐11 depressive episode and generalized anxiety disorder: The International Depression Questionnaire (IDQ) and the International Anxiety Questionnaire (IAQ)

alexandrossfakianakis shared this article with you from Inoreader The development and initial validation of self‐report measures of ICD‐11 depressive episode and generalized anxiety disorder: The International Depression Questionnaire (IDQ) and the International Anxiety Questionnaire (IAQ) via Journal of Clinical Psychology Abstract Background The new International Classification of Diseases came into effect in 2022 (ICD-11; World Health Organization, 2022) and included updated descriptions and diagnostic rules for "Depressive Episode" and "Generalized Anxiety Disorder." No self-report measures align with these disorders so this study reports the development and initial validation of the "International Depression Questionnaire" (IDQ) and "International Anxiety Questionnaire" (IAQ). Methods Items were developed that aligned to the ICD-11 descriptions and their performance was assessed using data from a community sample (N = 2058) that was representative of the United Kingdom adult population. Results Item response theory models indicated that the two scales were unidimensional, and the items performed well in terms of difficulty and discrimination. Estimates of internal reliability were high. Based on ICD-11 derived diagnostic algorithms, 7.4% met requirements for ICD-11 Depressive Episode and 7.1% for Generalized Anxiety Disorder. Conclusions The IDQ and the IAQ are short, easy to use, self-report measures aligned to the new and updated ICD-11 diagnostic descriptions. This study provides initial evidence that the scales produce scores that are reliable and valid. View on Web

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Bone vitality and vascularization of mandibular and maxillary bone grafts in maxillary sinus floor elevation: A retrospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Bone vitality and vascularization of mandibular and maxillary bone grafts in maxillary sinus floor elevation: A retrospective cohort study via Clinical Implant Dentistry and Related Research Abstract Objectives Mandibular retromolar (predominantly cortical) and maxillary tuberosity (predominantly cancellous) bone grafts are used in patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement. The aim of this retrospective cohort study was to investigate whether differences exist in bone formation and vascularization after grafting with either bone source in patients undergoing MSFE. Methods Fifteen patients undergoing MSFE were treated with retromolar (n = 9) or tuberosity (n = 6) bone grafts. Biopsies were taken 4 months postoperatively prior to dental implant placement, and histomorphometrically analyzed to quantify bone and osteoid area, number of total, apoptotic, and receptor activator of nuclear factor-κB ligand (RANKL)-positive osteocytes, small and large-sized blood vessels, and osteoclasts. The grafted area was divided in three regions (caudal-cranial): RI, RII, and RIII. Results Bone volume was 40% (RII, RIII) higher and osteoid volume 10% (RII) lower in retromolar compared to tuberosity-grafted areas. Total osteocyte number and number of RANKL-positive osteocytes were 23% (RII) and 90% (RI, RII) lower, but osteoclast number was higher (retromolar: 12, tuberosity: 0) in retromolar-grafted areas. The total number of blood vessels was 80% (RI) to 60% (RIII) lower, while the percentage of large-sized blood vessels was 86% (RI) to 25% (RIII) higher in retromolar-grafted areas. Number of osteocyte lacunae and apoptotic osteocytes were similar in both bone grafts used. Conclusions Compared to the retromolar bone, tuberosity bone showed increased bone vitality and vascularization in patients undergoing MSFE, likely due to faster bone remodeling or earlier start of new bone formation. Therefore, tuberosity bone grafts might perform better in enhancing bone regeneration. View on Web

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SARS‐CoV‐2 evolves to reduce but not abolish neutralizing action

alexandrossfakianakis shared this article with you from Inoreader SARS‐CoV‐2 evolves to reduce but not abolish neutralizing action via Journal of Medical Virology Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the hACE2 (human angiotensin-converting enzyme 2) receptor on the surface, and an eGFP reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivima b, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7-fold and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutr alization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants. This article is protected by copyright. All rights reserved. View on Web

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Efficacy and Safety of Radiofrequency Ablation of Thyroid Nodules: A Multi-institutional Prospective Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Efficacy and Safety of Radiofrequency Ablation of Thyroid Nodules: A Multi-institutional Prospective Cohort Study via Annals of Surgery - Most Popular Articles Background: Radiofrequency ablation (RFA) has been recently adopted into the practice of thyroidology in the United States, although its use as an alternative to traditional thyroid surgery in Asia and Europe came near the turn of the 21st century. In the United States, only a few studies with small sample sizes have been published to date. We examined outcomes of benign thyroid nodules treated with RFA from 2 North American institutions. Methods: We performed a prospective, multi-institutional cohort study of thyroid nodules treated with RFA between July 2019 and January 2022. Demographics, sonographic characteristics of thyroid nodules, thyroid function profiles, procedural details, complications, and nodule volume measurements at 1, 3, 6, and 12 months follow-up were evaluated. Adjusted multivariate logistic regression analysis was performed to identify sonographic features associated with treatment failure. Results: A total of 233 nodules were included. The median and interquartile range of volume reduction rate (VRR) at 1, 3, 6, and 12 months were 54% [interquartile range (IQR): 36%–73%], 58% (IQR: 37%–80%), 73% (IQR: 51%–90%), and 76% (IQR: 52%–90%), respectively (P View on Web

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