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Κυριακή 30 Οκτωβρίου 2022

Characterization of Leuconostoc mesenteroides MJM60376 as an oral probiotic and its anti‐biofilm activity

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Abstract

Lactic acid bacteria have been widely used as probiotics for improving gut health. However, studies on oral probiotics were very limited. In this study, 67 lactic acid bacteria (LAB) were isolated from fermented food and screened for antagonistic activity against Streptococcus mutans, the causative pathogen of dental caries. Leuconostoc mesenteroides MJM60376 showed the highest antagonistic activity against S. mutans KCTC3065. L. mesenteroides MJM60376 also showed oral probiotic characteristics including weak acid production, lysozyme tolerance, adhesion to oral epithelial cell (YD-38), antibiotic susceptibility, and good co-aggregation ability with S. mutans. Furthermore, the biofilm formation of S. mutans was significantly reduced when co-cultured with L. mesenteroides. Scanning electron microscopy analysis showed that amounts of attached bacteria of S. mutans and network-like structures were significantly reduced by L. mesenteroides MJM60376. Cell-free supernatant (CFS) of L. mesenteroides MJM60376 also greatly inhibited biofilm formation of S. mutans from the adherent stage, the activity remained even after it was treated with catalase, trypsin, or pH neutralized. Expression levels of biofilm formation-related genes were significantly reduced in S. mutans when it was treated with the CFS of L. mesenteroides MJM60376. Therefore, L. mesenteroides MJM60376 has great potential to be used as a multifunctional oral health ingredient.

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The Influence of Age on the Frequency of Rhythmic Masticatory Muscle Activity During Sleep in General Population differs from that in Clinical Research Samples

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Abstract

Introduction

During sleep, limb and jaw muscle motor activity can be quantified by electromyography (EMG). The frequency of periodic limb activity during sleep increases with age in both the general and clinical research populations. The literature is controversial regarding stability, over age, of the frequency of rhythmic masticatory muscle activity (RMMA), which is one biomarker of sleep bruxism (SB). The purpose of this retrospective sleep laboratory study was to assess if any change in RMMA frequency occurs over age in the general population (GP) and two clinical research (CR) samples.

Method

RMMA signals from polysomnography (PSG) recordings of 465 individuals, irrespective of SB awareness, were analysed. The sample comprised 164 individuals from the GP of Sao Paulo, and 301 individuals from Montreal and Osaka CR samples.

Data were divided into two subgroups, younger (15–39) and older (40–80) participants. RMMA was classified as low frequency (<2 events/hr) or high (>2 events/hr). Pearson correlation (R) and B (slope) analyses were performed with power estimations.

Results

In the GP sample, no significant change over age was noted in the RMMA index/year. In the CR samples, a significant reduction was observed in the RMMA index/year (-0.05) with age (R2=0.042; p<0.001; 3.5 to 1.5 RMMA/hr from 20 to 60 years old).

Conclusions

In the GP, the RMMA index remained stable over age. In the CR samples, a significant, reduction was observed. Prospective studies with multiple home sleep recordings, in both general and clinical research populations, are needed before extrapolating from the present findings.
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The evolution of fertility preservation care models in a large pediatric cancer and blood disorders center

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Abstract

Background

Children and adolescents who receive gonadotoxic treatments are at risk for future infertility. While there is a growing focus on integrating fertility preservation (FP) within pediatric cancer and blood disorder centers, wide variations in care models and methods exist across institutions. The purpose of this work is to describe the evolution of FP care models within a large pediatric hematology/oncology center.

Methods

Models of care and associated timeframes are described, including a pre-FP program model, establishment of a formal FP program, integration of nurse navigators, and the addition of FP consult stratification based on urgency (urgent/nonurgent). The number of patient consults within each model, patient sex, diagnosis (oncologic/hematologic), and consult timing (pre-gonadotoxic treatment/posttreatment completion) were abstracted from the clinical database.

Results

The number of annual consults increased from 24 during the pre-FP program model (2015) to 181 during the current care model (2020). Over time, the proportion of consults for females and patients with nonmalignant hematologic disorders increased. Patient stratification reduced the proportion of consults needing to be completed urgently from 75% at the advent of the FP program to 49% in the current model.

Conclusions

The evolution of care models within our FP program allowed for growth in the number of consults completed, expansion of services to more patients with nonmalignant hematologic disorders, and more consults for female patients. Nurse navigators play a critical role in care facilitating referrals, coordination, and patient education. Urgency stratification has allowed FP team members to manage increasing FP-related encounters.
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Off‐label pharmacological treatment for neuropathic pain: A Delphi study by the Spanish Pain Society Neuropathic Pain Task Force

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Abstract

Objectives

The use of off-label pharmacotherapies for neuropathic pain (NP) is growing relating to the many unmet needs of patients. However, clinical guidelines fail to address it, and the available evidence is sparse and fragmented. We arranged a formal expert consensus to address this controversial issue and provide some guidance on judicious use.

Methods

A two-round standard Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 40-item questionnaire prepared by the authors. Consensus on each statement was defined as at least either 80% endorsement or rejection after the second round.

Results

Forty-three and thirty-seven panelists participated in the first and second round, respectively. Consensus was reached in 34 out of 40 statements. Endorsed alternatives for unresponsive patients include non-gabapentinoid antiepileptics (oxcarbazepine and eslicarbazepine), venlafaxine, intravenous lidocaine (when doses can be optimized), and some vaporized cannabinoids (under appropriate surveillance). In addition, lacosamide, low-dose naltrexone, propofol or ketamine could prove beneficial if subjected to more research. Other options were rejected, and there was controversy about the usefulness of topical preparations.

Discussion

For patients who do not respond to standard NP treatments, some other viable pharmacological options can be attempted before advancing to other therapeutic stages. This may help patients who are reluctant to or have some contraindication for interventional therapies.
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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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