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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Crescent‐shaped skin paddle for a fibular flap: Avoiding skin grafting at the donor site

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Abstract

A fibular osteocutaneous flap is the mainstay of oromandibular reconstruction. This report aimed to present a crescent-shaped skin paddle, a novel fibular skin paddle designed to achieve both sufficient intraoral lining and primary closure of the donor site. A 3–5-cm-wide crescent-shaped skin paddle was harvested according to the locations of the distal septocutaneous perforators on preoperative color Doppler sonography. This narrow skin paddle fits well morphologically into the mucosal defect, enabling a reliable intraoral lining. This advantage becomes more evident when the mandibular defect crosses the midline or extends posteriorly to the maxillary tuberosity as the shape of the mucosal defect becomes arcuate. Primary closure of the donor site is easier to achieve because the required width of the crescent-shaped skin paddle is minimized. This method reduces donor-site morbidity associated with skin grafting while ensuring safe intraoral closure with a fibular osteocutaneous flap.

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Prognostic and therapeutic significance of XPO1 in T-cell lymphoma

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Publication date: Available online 27 April 2022

Source: Experimental Cell Research

Author(s): Danian Nie, Xiaohui Xiao, Jiaoting Chen, Shuangfeng Xie, Jie Xiao, Wenjuan Yang, Hongyun Liu, Jieyu Wang, Liping Ma, Yumo Du, Kezhi Huang, Yiqing Li

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Is inhaled zanamivir non-inferior to oral oseltamivir in the treatment of outpatients with influenza?

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Potentiation of antibiotic activity, and efflux pumps inhibition by (2E)‐1‐(4‐aminophenyl)‐3‐(4‐fluorophenyl)prop‐2‐en‐1‐one

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Abstract

In recent years, bacterial resistance to traditional drugs has increased, and the need to find new effective antibiotics to treat infections caused by multidrug-resistant bacteria has consequently become more important. The current study aimed to evaluate the potentiation of antibiotic activity and efflux pumps inhibition by (2E)-1-(4-aminophenyl)-3-(4-fluorophenyl)prop-2-en-1-one (PA-Fluorine) against the standard and resistant bacterial strains of Staphylococcus aureus and Escherichia coli. The association between PA-Fluorine and ampicillin reduced the MIC, showing a synergistic effect against Staphylococcus aureus. For Escherichia coli, PA-Fluoride did not show any significant results when associated with ampicillin. Ciprofloxacin and chlorpromazine showed synergy with PA-Fluorine on the two studied strains. An efflux pump mechanism was involved in the mechanism of action of chlorpromazine, norfloxacin, and ethidium bromide. PA-Fluorine synerg istically modulated norfloxacin and bromide. It was thus concluded that PA-Fluorine has the potential to enhance antibacterial activity when combined with antibiotics. Molecular docking studies showed the effect of intermolecular interactions of PA-Fluorine on the NorA and MepA efflux pumps. Physicochemical and pharmacokinetic properties were also obtained by ADMET studies for this chalcone, which presents be a strong candidate as an efflux pump inhibitor.

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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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