Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Tuesday, October 11, 2022

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

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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.

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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)

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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.

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

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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.

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The pathophysiological and immunological background of the monkeypox virus infection: An update

alexandrossfakianakis shared this article with you from Inoreader

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.

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

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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.

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

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imageBackground: 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
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Prevention of Incisional Hernias by Prophylactic Mesh-augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: Five-year Follow-up of a Randomized Controlled Trial

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imageIntroduction: The incidence of incisional hernias (IHs) after open repair of an abdominal aortic aneurysm (AAA) is high. Several randomized controlled trials have reported favorable results with the use of prophylactic mesh to prevent IHs, without increasing complications. In this analysis, we report on the results of the 60-month follow-up of the PRIMAAT trial. Methods: In a prospective, multicenter, open-label, randomized design, patients were randomized between prophylactic retrorectus mesh reinforcement (mesh group), and primary closure of their midline laparotomy after open AAA repair (no-mesh group). This article reports on the results of clinical follow-up after 60 months. If performed, ultrasonography or computed tomography were used for the diagnosis of IHs. Results: Of the 120 randomized patients, 114 were included in the intention-to-treat analysis. Thirty-three patients in the no-mesh group (33/58—56.9%) and 34 patients in the mesh group (34/56—60.7%) were evaluated after 5 years. In each treatment arm, 10 patients died between the 24-month and 60-month follow-up. The cumulative incidence of IHs in the no-mesh group was 32.9% after 24 months and 49.2% after 60 months. No IHs were diagnosed in the mesh group. In the no-mesh group, 21.7% (5/23) underwent reoperation within 5 years due to an IH. Conclusions: Prophylactic retrorectus mesh reinforcement after midline laparotomy for the treatment of AAAs safely and effectively decreases the rate of IHs. The cumulative incidence of IHs after open AAA repair, when no mesh is used, continues to increase during the first 5 years after surgery, which leads to a substantial rate of hernia repairs.
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