A novel MAP3K20 mutation causing centronuclear myopathy-6 with fiber-type disproportion in a Pakistani family

alexandrossfakianakis shared this article with you from Inoreader A novel <i>MAP3K20</i> mutation causing centronuclear myopathy-6 with fiber-type disproportion in a Pakistani family via Journal of Human Genetics - Issue - nature.com science feeds View on Web

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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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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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Efficacy of access flap and pocket elimination procedures in the management of peri‐implantitis – a systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Efficacy of access flap and pocket elimination procedures in the management of peri‐implantitis – a systematic review and meta‐analysis via Journal of Clinical Periodontology Abstract Objectives To evaluate the efficacy of access flap and pocket elimination procedures in the surgical treatment of peri-implantitis. Methods Systematic electronic searches (Central/Medline/Embase) up to March 2022 were conducted to identify prospective clinical studies evaluating surgical therapy (access flap or pocket elimination procedures) of peri-implantitis. Primary outcome measures were reduction of probing depth (PD) and bleeding on probing (BOP). Risk of bias was evaluated according to study design. Meta-analysis and meta-regression were performed. Results were expressed as standardized mean effect with 95% confidence intervals (CI). Results Evidence from studies directly comparing surgical with non-surgical therapy is lacking. Based on pre-post data originating from 13 prospective patient cohorts, pronounced reductions of PD (standardized mean effect: 2.2 mm; 95%CI 1.8, 2.7) and BOP% (27.0; 95%CI 19.8, 34.2) as well as MBL gain (0.2 mm; 95%CI -0.0, 0.5) were observed at evaluation time points ranging from 1 to 5 years. Wide prediction intervals suggested a high degree of heterogeneity. Reduction of mean PD increased by 0.7 mm (95%CI 0.5, 0.9) for every mm in increase of mean PD at baseline. During follow-up period ranging from 1 to 5 years, disease recurrence occurred frequently and implant loss was not uncommon. Conclusions Access flap and pocket elimination surgery are effective procedures in the management of peri-implantitis, although rates of disease recurrence during 5 years were high. Treatment outcomes were affected by baseline conditions. 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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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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The pathophysiological and immunological background of the monkeypox virus infection: An update

alexandrossfakianakis shared this article with you from Inoreader The pathophysiological and immunological background of the monkeypox virus infection: An update via Journal of Medical Virology Abstract In addition to the COVID-19 waves, the globe is facing global monkeypox (MPX) outbreak. MPX is an uncommon zoonotic infection characterized by symptoms similar to smallpox. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus that belongs to the genus Orthopoxvirus (OPXV). MPXV, which causes human disease, has been confined to Africa for many years, with only a few isolated cases in other areas. Outside of Africa, the continuing MPXV outbreak in multiple countries in 2022 is the greatest in recorded history. The current outbreak, with over ten thousand confirmed cases in over fifty countries between May and July 2022, demonstrates that MPXV may travel rapidly among humans and pose a danger to human health worldwide. The rapid spread of such outbreaks in recent times has elevated monkeypox to the status of a rising zoonotic disease with significant epidemic potential. While the MPXV is not as deadly or contagious as the variola virus that c auses smallpox, it poses a threat because it could evolve into a more potent human pathogen. This review assesses the potential threat to the human population and provides a brief overview of what is currently known about this re-emerging virus. By analyzing the biological effects of MPXV on human health, its shifting epidemiological footprint, and currently available therapeutic options, this review has presented the most recent insights into the biology of the virus. This study also clarifies the key potential causes that could be to blame for the present MPX outbreak and draw attention to major research questions and promising new avenues for combating the current monkeypox epidemic. This article is protected by copyright. All rights reserved. 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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