Πέμπτη 28 Απριλίου 2022

Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis ‐ an umbrella review

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Abstract

Background

The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated.

Objectives

This umbrella review aimed to (i) analyse the available relevant systematic reviews in an attempt to determine the association between genotype and allelic distribution of different single nucleotide polymorphisms (SNPs) and the development of AP, (ii) report deficiencies and gaps in knowledge in this area, and (iii) present recommendations to conduct future clinical studies and systematic reviews.

Methods

A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Database of Systematic Reviews, from inception to October 2021, with no language restrictions, including a grey literature search. Systematic reviews with/without meta-analysis evaluating genotype and allelic distribution of different SNPs between adult patients with/ without AP were included. All other type of studies were excluded. The methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) - 2 tool. Two independent reviewers were involved in study selection, data extraction, and appraising the included reviews; disagreements were resolved by a third reviewer.

Results

The current study includes five systematic reviews. Three reviews performed meta-analysis. Three reviews were graded by AMSTAR 2 as 'critically low' quality, whereas other two were graded as 'low' and 'moderate' quality. Two reviews indicated that carriers of specific genotypes and alleles of tumour necrosis factor – alpha (TNF-α) -308 G>A and interleukin 1-beta (IL-1β) +3954 C/T gene polymorphisms are more susceptible to an acute and persistent form of AP. However, high heterogeneity was observed.

Discussion

The statistical heterogeneity within included systematic reviews was a consequence of clinical and methodological diversity amongst primary studies. Although some of included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G>A and IL-1β +3954 C/T SNPs are more susceptible to AP, their conclusions should be interpreted with caution.

Conclusions

No candidate genes could be identified as a definitive genetic risk or protective factor for the development and progression of AP, and further high-quality genome-wide association studies are warranted.

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Inverse co-expression of EZH2 and acetylated H3K27 in prostatic tissue

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Publication date: Available online 27 April 2022

Source: Annals of Diagnostic Pathology

Author(s): Andrii Puzyrenko, Suresh N. Kumar, Cooley G. Pantazis, Kenneth A. Iczkowski

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Airflow patterns in double occupancy patient rooms may contribute to roommate-to-roommate transmission of severe acute respiratory syndrome coronavirus 2

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Abstract
Background
Hospitalized patients are at risk to acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from roommates with unrecognized coronavirus disease 2019 (COVID-19). We hypothesized that airflow patterns might contribute to SARS-CoV-2 transmission in double occupancy patient rooms.
Methods
A device emitting condensed moisture was used to identify airflow patterns in double occupancy patient rooms. Simulations were conducted to assess transfer of fluorescent microspheres, 5% sodium chloride aerosol, and aerosolized bacteriophage MS2 between patient beds 3 meters apart and to assess the effectiveness of privacy curtains and portable air cleaners in reducing transfer.
Results
Air flowed from inlet vents in the center of the room to an outlet vent near the door, resulting in air currents flowing toward the bed adjacent to the outlet vent. Fluorescent microspheres (212-250 µm diameter), 5% sodium chlor ide aerosol, and aerosolized bacteriophage MS2 released from the inner bed were carried on air currents toward the bed adjacent to the outlet vent. Closing curtains between the patient beds reduced transfer of each of the particles. Operation of a portable air cleaner reduced aerosol transfer to the bed adjacent to the outlet vent but did not offer a benefit over closing the curtains alone, and in some situations resulted in an increase in aerosol exposure.
Conclusion
Airflow patterns in double occupancy patient rooms may contribute to risk for transmission of SARS-CoV-2 between roommates. Keeping curtains closed between beds may be beneficial in reducing risk.
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Cochlear Fluid Spaces and Structures of the  Gerbil High-Frequency Region Measured Using Optical Coherence Tomography (OCT)

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In this study, optical coherence tomography was employed to obtain volumetric images of the high-frequency hook region of the gerbil cochlea, as viewed through the round window, with far better resolution capability than had been possible before. The anatomical structures and fluid spaces of the organ of Corti were segmented and quantified in vivo and over a 90-min postmortem period. We find that the arcuate-zone and pectinate-zone widths change very little postmortem. The volume of the scala tympani between the round-window membrane and basilar membrane and the volume of the inner spiral sulcus decrease in the first 60-min postmortem. While textbook drawings of the  mammalian organ of Corti and cortilymph prominently depict the tunnel of Corti, the outer tunnel is typically missing. This...
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Electrical and Immunohistochemical Properties of Cochlear Fibrocytes in 3D Cell Culture and in the Excised Spiral Ligament of Mice

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AbstractFibrocyte degeneration in the cochlear lateral wall is one possible pathology of age-related metabolic hearing loss (presbycusis). Within the lateral wall fibrocytes play a role in potassium recycling and maintenance of the endocochlear potential. It has been proposed that cell replacement therapy could prevent fibrocyte degeneration in the CD/1 mouse model of hearing loss. For this to work, the replacement fibrocytes would need to take over the structural and physiological role of those lost. We have grown lateral wall fibrocytes from neonatal CD/1 mice in a 3D-collagen gel culture with the aim of assessing their functional similarity to native lateral wall fibrocytes, the latter in a slice preparation and in excised spiral ligament pieces. We have compared cultured and native fib...
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Evidence for Loss of Activity in Low-Spontaneous-Rate Auditory Nerve Fibers of Older Adults

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This study is the first to successfully assess forward-masked recovery functions in both younger and older adults and provides important insights into the structural and functional changes occurring in the AN with increasing age. (Source: JARO - Journal of the Association for Research in Otolaryngology)
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Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones During Bone Conduction Stimulation

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AbstractBone conduction (BC) is heavily relied upon in the diagnosis and treatment of hearing loss, but is poorly understood. For example, the relative importance and frequency dependence of various identified BC sound transmission mechanisms that contribute to activate the cochlear partition remain unknown. Recently, we have developed techniques in fresh human cadaveric specimens to directly measure scalae pressures with micro-fiberoptic sensors, enabling us to monitor the input pressure drive across the cochlear partition that triggers the cochlear traveling wave during air conduction (AC) and round-window stimulation. However, BC stimulation poses challenges that can result in inaccurate intracochlear pressure measurements. Therefore, we have developed a new technique described here tha...
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gom1 Mutant Mice as a Model of Otitis Media

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AbstractOtitis media (OM) disease is a common cause of hearing loss that is primarily the result of middle ear infection. At present, our understanding of the mechanisms leading to OM is limited due to the lack of animal models of OM with effusion (OME). Here, we report that the mice withgenetic otitis media one (gom1) mutants are prone to OM.gom1 Mice were produced by theN-ethyl-N-nitrosourea (ENU) mutagenesis program as an animal model to study OM. These mice demonstrate many common features of OM, such as middle ear effusion and hearing impairment. We revealed thatgom1 mice display various signs of middle ear and inner ear dysfunctions, including elevated thresholds of auditory-evoked brainstem response (ABR) and lack of cochlear microphonic responses. Decreased compliance in  tympanom...
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Influence of Grading on Management and Outcome in Mucoepidermoid Carcinoma of the Parotid—A Multi‐institutional Analysis

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Objective

To evaluate clinical outcome of low (G1), intermediate (G2), and high-(G3) grade mucoepidermoid carcinomas (MEC) of the parotid gland.

Study Design

Retrospective chart review including 212 patients. Clinicopathological data was statistically analyzed regarding grading, overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS).

Results

105 (49.5%) G1, 73 (34.5%) G2, and 34 (16%) G3 MEC were included and 56 (26.4%) patients presented with neck node metastases. The risk of occult nodal metastases was significantly associated with grading and increased from 9.2% in G1 to 26.7% and 27.8% in G2 and G3 tumors, respectively (p = 0.008). Elective periparotid and cervical lymph node dissection was performed in 170 (80.2%) and 70 (33%) patients, respectively. All patients with positive periparotid nodes when subjected to an additional neck dissection had associated cervical neck node involvement (p < 0.001). Grading was an independent significant prognostic factor for OS (HR 4.05; 95%CI: 1.15–14.35; p = 0.030) and DSS (HR 17.35; 95%CI: 1.10–273.53; p = 0.043). In a subgroup analysis, elective neck dissection (END) was also significantly associated with a better DFS (p = 0.041) in neck node-negative G1 MECs.

Conclusion

The risk of occult nodal metastasis in intermediate-grade MEC is as high as in high-grade MEC and that END in G1 tumors is associated with a prolonged DFS. Additionally, periparotid node involvement seems to be a predictor for positive neck node involvement. This study presents some preliminary data to consider END in clinically neck node negative patients with parotid MEC; however, larger series are needed.

Level of Evidence

3 Laryngoscope, 2022

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Blinatumomab overcomes poor prognostic impact of measurable residual disease in pediatric high‐risk first relapse B‐cell precursor acute lymphoblastic leukemia

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Abstract

Background

Blinatumomab, a CD3/CD19 BiTE® (bispecific T cell engager) molecule, was superior to high-risk third course consolidation chemotherapy (HC3) in prolonging event-free survival (EFS) in children with high-risk first relapse B-cell precursor acute lymphoblastic leukemia (B-ALL). Here, we report results from a post hoc measurable residual disease (MRD) analysis of this phase 3 study (NCT02393859).

Procedure

Children >28 days and <18 years with high-risk first-relapse B-ALL in cytomorphological complete remission (M1 marrow, <5% blasts) or with M2 marrow (≥5% and <25% blasts) after induction and two cycles of high-risk consolidation chemotherapy (baseline) were enrolled in this trial. Patients received one cycle of blinatumomab (15 μg/m2/day, 4 weeks, continuous intravenous infusion) or HC3. The primary endpoint was EFS. In this post hoc analysis, patients with MRD <10–4 by PCR were grouped as having positive but not quantifiable (pbnq) or undetectable disease.

Results

A higher proportion of patients with MRD <10–4 had undetectable versus pbnq disease after blinatumomab (day 29) than after HC3 (p = 0.0367). Of the 22 patients with MRD ≥10–4 at baseline who achieved MRD remission after blinatumomab, 20 (91%) achieved MRD <10–4 remission by day 15. Patients treated with blinatumomab had improved EFS and overall survival compared with those treated with HC3 independent of end-of-induction or baseline (end-of-second consolidation) MRD levels.

Conclusions

Blinatumomab was more efficacious than HC3 regardless of MRD status before treatment. These data support the role of blinatumomab in inducing deep MRD remission, negating the poor prognostic value of MRD.

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Τετάρτη 27 Απριλίου 2022

Cell pyroptosis in picornavirus and its potential for treating viral infection

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Abstract

Cell pyroptosis has received increased attention due to the associations between innate immunity and disease, and it has become a major focal point recently due to in-depth studies of cancer. With increased research on pyroptosis, scientists have discovered that it has an essential role in viral infections, especially in the occurrence and development of some picornavirus infections. Many picornaviruses, including Coxsackievirus, a71 enterovirus, human rhinovirus, encephalomyocarditis virus, and foot-and-mouth disease virus induce pyroptosis to varying degrees. This review summarized the mechanisms by which these viruses induce cell pyroptosis, which can be an effective defense against pathogen infection. However, excessive inflammasome activation or pyroptosis also can damage the host's health or aggravate disease progression. Careful approaches that acknowledge this dual effect will aid in the exploration of picornavirus infections and the mechanisms that produce the inflammatory response. This information will promote the development of drugs that can inhibit cell pyroptosis and provide new avenues for future clinical treatment.

This article is protected by copyright. All rights reserved.

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Impact of SARS‐CoV‐2 Mu variant on vaccine effectiveness: a comparative genomics study at the peak of the third wave

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Abstract

We assessed the circulation of SARS-CoV-2 variants amongst vaccinated military personnel in Bogotá, Colombia to evaluate the mutations of certain variants and their potential for breakthrough infection in vaccinated subjects. We observed that in vaccinated individuals the most frequent infecting lineage was Mu (B.1.621 and B.1.621.1). The above possibly associated with specific mutations that confers it with vaccine-induced immune escape ability. Our findings highlight the importance of how genomic tracking coupled with epidemiological surveillance can assist in the study of novel emerging variants (e.g. Omicron) and their impact on vaccination efforts worldwide.

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