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Κυριακή 30 Οκτωβρίου 2022

Computational fluid dynamics and NOSE scale to assess nasal respiratory function, and correlation with linear maxillary measurements after surgically assisted rapid maxillary expansion

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Nasal obstruction is common in patients with a transverse maxillary deficiency. The aim of this study was to determine the variation in nasal airway resistance in adult patients with a transverse maxillary deficiency before and after surgically assisted rapid maxillary expansion (SARME) by computational fluid dynamics (CFD) using computed tomography scans, and to correlate this variation with maxillary linear measurements obtained by means of plaster models. The subjective symptoms of nasal obstruction were also analysed using a visual analogue scale (VAS) for nasal breathing and the Nasal Obstruction Symptom Evaluation (NOSE) scale. (Source: International Journal of Oral and Maxillofacial Surgery)
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Παρασκευή 28 Οκτωβρίου 2022

Cytosolic DNA Sensors Activation Inhibits HIV Infection of Macrophages

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Abstract

Cytosolic recognition of microbial DNA in macrophages results in the activation of the interferon (IFN) dependent antiviral innate immunity. Here, we examined whether activating DNA sensors in peripheral blood monocyte-derived macrophages (MDMs) can inhibit HIV. We observed that the stimulation of MDMs with poly(dA:dT) or poly(dG:dC) (synthetic ligands for the DNA sensors) inhibited HIV infection and replication. MDMs treated with poly(dA:dT) or poly(dG:dC) expressed higher levels of both type I and type III IFNs than untreated cells. Activation of the DNA sensors in MDMs also induced the expression of the multiple intracellular anti-HIV factors, including IFN-stimulated genes (ISGs: ISG15, ISG56, Viperin, OAS2, GBP5, MxB and Tetherin) and the HIV restriction microRNAs (miR-29c, miR-138, miR-146a, miR-155, miR-198, and miR-223). In addition, the DNA sensor activation of MDM upregulated the expression of the CC chemokines (RANTES, MIP-1α, MIP-1β), the ligan ds for HIV entry coreceptor CCR5. These observations indicate that the cytosolic DNA sensors have a protective role in the macrophage intracellular immunity against HIV and that targeting the DNA sensors has therapeutic potential for immune activation-based anti-HIV treatment.

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Impact of Serial Intralesional Steroid Injections on Idiopathic Subglottic Stenosis

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Objectives

Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea.

Methods

Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan–Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score. Within patients undergoing SILSI, demographics, time from last procedure, and PEF at initiation of SILSI were evaluated to determine the effect on recurrence.

Results

Two hundred and ninety patients were included, 238 undergoing endoscopic dilation alone and 52 undergoing dilation and SILSI. No differences in baseline characteristics were observed. There was no difference in time to recurrence (hazard ratio: 0.64; p = 0.183). There were no differences in PEF or CCQ across the 2.5-year study period. Among 52 patients undergoing SILSI, PEF at the time of starting SILSI did not affect recurrence (χ 2 = 0.09, p = 0.77).

Conclusion

Patients undergoing and not undergoing SILSI had similar times to recurrence, PEF, and CCQ. Factors predicting recurrence among patients undergoing SILSI were not identified. These results support a randomized controlled trial with a uniform SILSI protocol to quantify the effects of SILSI on objective and subjective outcomes and help determine which iSGS patients benefit most.

Level of Evidence

3 Laryngoscope, 2022
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Diagnostic performance of magnetic resonance imaging for degenerative temporomandibular joint disease

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Abstract

Background

Degenerative joint disease (DJD) of the temporomandibular joint (TMJ) is an important type of temporomandibular disorders (TMDs) potentially leading to orofacial pain and jaw dysfunction. Magnetic resonance imaging (MRI) is important in TMD diagnosis; however, its diagnostic ability for DJD remains unknown.

Objective

To explore the utility of MRI in diagnosing DJD according to the latest diagnostic criteria for TMD and detecting condylar bone abnormalities and their severity.

Methods

Overall, 122 participants were examined using cone-beam computed tomography (CBCT) and MRI. The sensitivity, specificity, and accuracy of MRI for detecting DJD and different types of TMJ condylar bone abnormalities were calculated (considering CBCT as gold standard); in addition, we tested MRI and CBCT's consistency in scoring five types of condylar bone abnormalities.

Results

The sensitivity and specificity of MRI for DJD were 95.3% and 43.1%, respectively.The MRI sensitivities for condylar flattening, erosion, osteophytes, sclerosis, and cysts were 98.6%, 96.2%, 79.4%, 50%, and 79.2% (specificity, 53.6%, 48.3%, 81.6%, 83.3%, and 88.2%, respectively), respectively. The consistency between MRI and CBCT in assessing the severity of condylar bone abnormalities was fair-to-moderate (kappa coefficient: 0.278-0.491). The inter-observer consistency for CBCT was good, whereas for MRI it was relatively poor.

Conclusion

MRI can detect DJD and condylar bone abnormalities. However, MRI could not efficiently detect the severity of condylar bone abnormalities.
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Broadly Neutralizing Antibodies for HIV Treatment: Broad in Theory, Narrow in Reality

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Abstract
In this viewpoint we briefly review the status of antiretroviral therapy, its unmet needs, and the role that broadly neutralizing antibodies (bNAbs) might have in the near future for the treatment of HIV. We summarize advances in the development of bNAbs as antiretroviral therapy, the results of main clinical trials of bNAbs for HIV treatment and prevention, and its role in cure trials. The limitations of broadly neutralizing antibodies are the current need for primary re sistance testing, the still unclear number of antibodies that must be combined, the lack of penetration in anatomical reservoirs and the role they might play in cure studies. We compare the advantages and disadvantages of "classical ART" and therapy based on broadly neutralizing antibodies. We conclude that broadly neutralizing antibodies still need considerable improvements before they can be considered an alternative to "classical ART".
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Τετάρτη 26 Οκτωβρίου 2022

LANA regulates miR‐155 /GATA3 signaling axis by enhancing c‐Jun/c‐Fos interaction to promote the proliferation and migration of KSHV‐infected cells

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Abstract

Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA-binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV-infected cells, while microRNA-155 (miR-155) was highly expressed in KS serum and KSHV-infected cells. miR-155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV-encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV-infected cells by regulating the miR-155/GATA3 axis. Regarding the molecular mechanism, c-Jun and c-Fos interact to form a complex. LANA up-regulates the expression of c-Jun and c-Fos and enhances the formation of c-Jun/c-Fos complex. The complex binds to the -95 ~ -100 bp site of miR-155 promoter and transcriptionally activates miR-155. All in a ll, LANA enhances the c-Jun/c-Fos interaction, resulting in enhanced transcriptional regulation of miR-155 by the c-Jun/c-Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV-infected cells. The discovery of LANA/c-Jun/c-Fos/miR-155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS.

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Changes in the syphilis reactive plasma regain (RPR) titre between diagnosis and treatment

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Abstract
Background
We compared the reactive plasma regain (RPR) titre on the day of initial presentation to the day of syphilis treatment to inform clinical practice as to whether a repeat RPR test should be recommended.
Methods
We undertook a retrospective study between 1-March-2011 and 31-December-2020 at the Melbourne Sexual Health Centre in Australia among individuals who received syphilis serology on the day of initial presentation and the day of treatment, if it were within 14 days after initial presentation. We calculated the percentage of individuals with a four-fold or greater RPR change, stratified by the time between initial presentation and treatment, and syphilis stages.
Results
Of the 766 included syphilis cases, the median number of days between initial presentation and treatment was 6 (IQR = 5-7). There were 14.8% (n = 113) of cases that had a four-fold increase o r decrease between the day of initial presentation and the day of treatment. The number of cases with a 4-fold increase or decrease in RPR titre increased with increasing number of days between the day of initial presentation and day of treatment, i.e., 4.1% (n = 6) within 1-3 days after initial presentation to 25.7% (n = 27) with 10-14 days after initial presentation (ptrend < 0.0001). There was no significant difference in the number of cases with 4-fold increase or decrease in RPR between syphilis stages (p = 0.37).
Conclusion
Our data support the recommendation of repeating the RPR titre if the day of initial presentation and treatment are different, even when treatment is within a few days of the initial presentation.
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Exhaled Breath Aerosol Shedding by Highly Transmissible Versus Prior SARS-CoV-2 Variants

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Abstract
Background
Aerosol inhalation is recognized as the dominant mode of SARS-CoV-2 transmission. Three highly transmissible lineages evolved during the pandemic. One hypothesis to explain increased transmissibility is that natural selection favors variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. We aimed to measure the infectivity and rate of SARS-CoV-2 shedding into exhaled breath aerosol (EBA) by individuals during the Delta and Omicron waves and compared those rates with those of prior SARS-CoV-2 variants from our previously published work.
Methods
COVID-19 cases (n = 93, 32 vaccinated and 20 boosted) were recruited to give samples, including 30-minute breath samples into a Gesundheit-II exhaled breath aerosol sampler. Samples were quantified for viral RNA using RT-PCR and cultured for virus.
Results
Alpha (n = 4), Delta ( n = 3), and Omicron (n = 29) cases shed significantly more viral RNA copies into exhaled breath aerosols than cases infected with ancestral strains and variants not associated with increased transmissibility (n = 57). All Delta and Omicron cases were fully vaccinated and most Omicron cases were boosted. We cultured virus from the EBA of one boosted and three fully vaccinated cases.
Conclusions
Alpha, Delta, and Omicron independently evolved high viral aerosol shedding phenotypes, demonstrating convergent evolution. Vaccinated and boosted cases can shed infectious SARS-CoV-2 via EBA. These findings support a dominant role of infectious aerosols in transmission of SARS-CoV-2. Monitoring aerosol shedding from new variants and emerging pathogens can be an important component of future threat assessments and guide interventions to prevent transmission.
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The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: a prospective case‐control study

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Abstract

Aim

To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction.

Methodology

This is a prospective case-control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators were examined longitudinally in all subjects during 6 visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analyzed by linear regression analyses and linear mixed model analyses.

Results

A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, G-CSF (P<0.001), IL-1β (P=0.03) and IL-4 (P=0.01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e., three months after the tooth extraction, showed a significant reduction in IL-10 (P=0.03) and IL-12p70 (P=0.01).

Conclusions

The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low-grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis.
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Subgingival host‐microbiome metatranscriptomic changes following scaling and root planning in Grade II/III Periodontitis

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Abstract

Aims

To assess the effects of scaling and root planning (SRP) on the dynamics of gene expression by the host and the microbiome in subgingival plaque samples.

Methods

Fourteen periodontitis patients were closely monitored in the absence of periodontal treatment for 12 months. During this period, comprehensive periodontal examination and subgingival biofilm sample collection were performed bi-monthly. After 12 months, clinical attachment level (CAL) data was compiled and analyzed using linear mixed models (LMM) fitted to longitudinal CAL measurements for each tooth site. LMM classified sites as stable (S), progressing (P), or fluctuating (F). After 12 month visit, subjects received SRP and at 15 months they received comprehensive examination and supportive periodontal therapy (SPT). Those procedures were repeated at the 18 month visit, when patients were also sampled. Each patient contributed with one S, one P and one F site collected at 12 and 18 month visits. Samples were analyzed using Dual RNA-Sequencing to capture host and bacterial transcriptomes simultaneously.

Results

Microbiome and host response behavior were specific to the site's progression classification (i.e., S, P or F). Microbial profiles of pre and post-treatment samples exhibited specific microbiome changes, with progressing sites showing the most significant changes. Among them, P. gingivalis was reduced after treatment, while F. nucleatum showed an increase in proportion. Transcriptome analysis of the host response showed that IL-17, TNF signaling pathways, and neutrophil extracellular trap (NETs) formation were the primary immune response activities impacted by periodontal treatment.

Conclusion

Scaling and root planing resulted in a significant "rewiring" of host and microbial activities in the progressing sites, while in stable and fluctuating sites, the restructuring of the microbiome was minor.

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