Δευτέρα 7 Νοεμβρίου 2022

Evaluation of the transdentinal capability of the intrinsic antibacterial cetylpyridinium chloride/cholesterol sterosomes in vitro and in vivo

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Abstract

Abstract

Aim

Dentinal tubules serve as disease-causing channels for infiltration and penetration of bacteria and their by-products; which are regarded as the major driver of pathogenesis in pulpal inflammation and infection. In this study, we aimed to evaluate the transdentinal potential of nanoscale cetylpyridinium chloride/cholesterol (CPC/Chol) sterosomes, which are a recently developed type of cationic non-phospholipid liposomal nanocarrier; as well as their intrinsic and universal antibacterial activity.

Methodology

CPC/Chol sterosomes were formulated, with a hydrodynamic diameter of 134 ± 4 nm, a low polydisperse index of 0.161 ± 0.007, and a positive zeta potential of 41 ± 3 mV at pH 7.4. Transdentinal diffusion ability of sterosomes was evaluated using human dentine blocks in vitro, and Wistar rat molar teeth in vivo. The intrinsic antibacterial activities of CPC/Chol sterosomes against E. faecalis, S. mutans, F. nucleatum, and P. gingivalis were further examined.

Results

CPC/Chol sterosomes successfully penetrated through the dentinal tubules, and diffused into the pulp, which could be internalized by dental pulp cells with a high efficiency. Additionally, they exhibited substantial levels of intrinsic antibacterial activity against these Gram-positive and Gram-negative endodontic bacteria and their biofilms.

Conclusions

Given its high penetration and diffusion ability through the dentine and pulp, great potential for multi-drug delivery, and distinct intrinsic antibacterial activity; sterosome-based nanocarriers might serve as a promising therapeutic strategy aimed at targeting various specific pathways associated with pulpal diseases. This will help determine and characterize the most appropriate prophylactic and therapeutic targets for early intervention in our future dentistry practice.

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Κυριακή 6 Νοεμβρίου 2022

Characteristics of Orbital Injuries Associated with Maxillofacial Trauma

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Introduction

The incidence of ocular injury associated with maxillofacial trauma remains poorly defined, with reported rates ranging from 0.8% to 92%. Our study aims to more accurately characterize ocular injuries associated with midface fractures.

Methods

We performed a retrospective review of 1677 patients from 2015 to 2020 with midface fractures at a Level I trauma center. Isolated nasal bone and frontal process of the maxilla fractures were excluded. Demographic information, mechanism of injury, need for surgery, and ophthalmologic findings were documented. Statistical analysis was conducted using SPSS.

Results

773 patients between the ages of 15 and 92 were identified. Trauma most commonly resulted from assault (63.8%). The association between the mechanism of injury and ocular injury was statistically significant (p = 0.003), with 78.6% of gunshot wounds and 44.3% of assault patients having an ocular injury. The Ophthalmology service evaluated 62.6% of cases preoperatively. Minor ocular injury occurred in 36% of patients, including 46.1% of isolated orbital floor, and 28.2% of zygomaticomaxillary complex fractures. Major ocular injury occurred in 10.5% of patients.

Conclusions

Over 10% of patients with midface fractures were found to have major ocular injuries. Ophthalmologic exams should be performed for all patients with midface fractures to guide clinical decision making and prevent further intraoperative ocular insults.

Level of Evidence

Level 4. This study represents a retrospective cohort study analyzing ocular injuries detected in patients presenting to a Level I trauma center with maxillofacial fractures between 2015 and 2020 Laryngoscope, 2022

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Improving Methods of Identifying Anaphylaxis for Medical Product Safety Surveillance Using Natural Language Processing and Machine Learning

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Abstract
We sought to determine whether machine learning and natural language processing (NLP) applied to electronic medical records could improve performance of automated healthcare claims-based algorithms to identify anaphylaxis events using data on 516 patients with outpatient, emergency department, or inpatient anaphylaxis diagnosis codes during 2015-2019 in two integrated healthcare institutions in the Northwest United States. We used one site's manually reviewed gold standard outcomes data for model development and the other's for external validation based on cross-validated (cv) area under the receiver operating characteristic curve (cv AUC), positive predictive value (PPV), and sensitivity. In the development site 154 (64%) of 239 potential events met adjudication criteria for anaphylaxis compared to 180 (65%) of 277 in the validation site. Logistic regression models using only structured claims data achieved a cv-AUC of 0.58 (95% CI: 0.54, 0. 63). Machine learning improved cv-AUC to 0.62 (0.58, 0.66); incorporating NLP-derived covariates further increased cv AUCs to 0.70 (0.66, 0.75) in development and 0.67 (0.63, 0.71) in external validation data. A classification threshold with cv-PPV of 79% and cv-sensitivity of 66% in development data had cv-PPV of 78% and cv-sensitivity of 56% in external data. Machine learning and NLP-derived data improved identification of validated anaphylaxis events.
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Transcriptional analysis of the mfa‐cluster genes in Porphyromonas gingivalis strains with one and two mfa5 genes

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Abstract

The Porphyromonas gingivalis Mfa1 fimbria is composed of the Mfa1 to Mfa5 proteins, encoded by the mfa1 to mfa5 genes, respectively, which are tandemly arranged on chromosomes. A recent study discovered that many P. gingivalis strains possess two mfa5 genes (called herein mfa5-1 and mfa5-2), which are also in tandem. This study examined the transcriptional unit and activity of mfa-cluster genes in strains with one (the ATCC 33277 and TDC60 strains) and two (the HG66 and A7436 strains) mfa5 genes. Complementary DNA was prepared from the total RNA extracted from the bacterial cells in the logarithmic growth phase using a random primer. PCR analysis for the intergenic regions from mfa1 to mfa5 or mfa5-2 showed that mfa1 to mfa5 or mfa5-2 formed a polycistronic gene cluster. Quantitative real-time PCR showed that the mfa1 transcription was 5–10 times higher than tha t of mfa2 in all the strains. However, mfa2 to mfa5 mostly showed a comparable expression. Both mfa5 genes were comparably transcribed in HG66 and A7436 strains. The transcriptional levels were almost consistent with the respective protein expression levels. In silico analysis identified a transcriptional terminator structure in the intergenic region between mfa1 and mfa2 that was probably responsible for the decreased transcription rate of mfa2 and the downstream genes.

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Endoscopic transoral approach to the lateral poststyloid space

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Abstract

The lateral poststyloid space (LPSS) located at the posterolateral aspect of the styloid process. This study aims to explore the anatomical relationships in LPSS via a transoral corridor, providing reference for addressing lesions extending to this region. An endoscopic transoral approach for exposure of the LPSS was performed on 6 cadaveric specimens (12 sides). Related landmarks were explored, and transoral extirpation of tumors extended into LPSS was employed in 12 patients. The deep lobe of the parotid gland, extratemporal facial nerve, and the accompanying artery in the LPSS were sufficiently exposed via the transoral corridor in all 12 cadaveric sides. The transoral corridor provided adequate exposure for tumors extending to the LPSS, and en bloc resection was achieved in these 12 patients. No facial nerve or vascular injury occurred, and no recurrence observed in this cohort with an average follow-up of 26 months. An endoscopic transoral approach provides a direct access to the LPSS. Appreciation of the anatomical relationships within the LPSS is valuable for employing a transoral extirpation of tumors extending to this specific region.

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Πέμπτη 3 Νοεμβρίου 2022

Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir

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Abstract
A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, IV remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery.
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Vaccine effectiveness against influenza A(H3N2)-associated hospitalized illness, United States, 2022

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Abstract
Background
The COVID-19 pandemic was associated with historically low influenza circulation during the 2020–2021 season, followed by increase in influenza circulation during the 2021–2022 US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain.
Methods
To understand the effectiveness of the 2021–2022 vaccine against hospitalized influenza illness, a multi-state sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness (ARI) and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative controls, adjusting for confounders. A separate analysis was performed to illustrate bias introduced by includin g SARS-CoV-2 positive controls.
Results
A total of 2334 patients, including 295 influenza cases (47% vaccinated), 1175 influenza- and SARS-CoV-2 negative controls (53% vaccinated), and 864 influenza-negative and SARS-CoV-2 positive controls (49% vaccinated), were analyzed. Influenza VE was 26% (95%CI: -14 to 52%) among adults aged 18-64 years, -3% (95%CI: -54 to 31%) among adults aged ≥65 years, and 50% (95%CI: 15 to 71%) among adults 18-64 years without immunocompromising conditions. Estimated VE decreased with inclusion of SARS-CoV-2-positive controls.
Conclusions
During a season where influenza A(H3N2) was antigenically different from the vaccine virus, vaccination was associated with a reduced risk of influenza hospitalization in younger immunocompetent adults. However, vaccination did not provide protection in adults ≥65 years of age. Improvements in vaccines, antivirals, and prevention strategies are warranted.
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