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Τετάρτη 19 Οκτωβρίου 2022

Sequence Analysis of Epstein‐Barr virus RPMS1 Gene in malignant hematopathy

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Abstract

The RPMS1 gene is the only member of the BamHI-A rightward transcripts (BARTs) family for which a full-length cDNA has been identified, and RPMS1 transcript has been confirmed in many EBV-positive malignancies. However, the effects of sequence variations of RPMS1 in hematological malignancies and their biological significance are unclear. To explore the association between RPMS1 gene variations and hematological malignancy, the RPMS1 gene of 391 EBV-positive samples from patients with EBV-positive leukemia, myelodysplastic syndromes (MDS) and lymphoma in northern China were sequenced. On the basis of phylogenetic tree and mutation characteristics of RPMS1, all the sequences were divided into five major types: RPMS1-A, RPMS1-B, RPMS1-C, RPMS1-E, and RPMS1-F. RPMS1-A type, similar to the prototype B95-8, was identified in 71.87% (281/391) of samples and was the major typ e in all subpopulations. The frequency of RPMS1-F type was significantly higher in all malignant hematopathy groups than in healthy donors. The Hodgkin lymphoma (HL) group contained more RPMS1-F than other malignant hematopathy groups, and acute myeloid leukemia (AML) contained more RPMS1-C type than other malignant hematopathy groups. Therefore, RPMS1-A is the main type of RPMS1 gene in northern China, and RPMS1-F may be associated with hematologic malignancies.

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Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B

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Abstract

Objectives

We aimed to develop and validate a novel combined score to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B (CHB).

Methods

The serum levels of hub genes were examined by qRT-PCR in three cohorts of CHB patients.

Results

For significant liver fibrosis (≥S2), the areas under the receiver operating characteristics curves (AUROCs) of the combined score were 0.838, 0.842 and 0.881 in the three cohorts, respectively. And for advanced liver fibrosis (≥S3), the AUROCs were 0.794, 0.801 and 0.901, respectively. Compared with the results of AUROCs for aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) in the validation cohorts, better clinical diagnostic value for assessing the progression of liver fibrosis was found in the combined score. Additionally, univariate ordered logistic regression analysis indicated that the combined score could serve as a more superior and stable risk factor than APRI and FIB-4 in the assessment of liver fibrosis. For CHB patients with normal alanine aminotransferase (ALT), our results further emphasized the diagnostic value of the combined score for significant fibrosis (≥S2) and advanced fibrosis (≥S3). Moreover, it was found that patients with the high combined score, who were associated with the advanced fibrosis stage, had higher levels of drug sensitivity and immune checkpoint expression.

Conclusion

The novel combined score could serve as a potential biomarker and contribute to improving the assessment of fibrosis stage in CHB patients.

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Cholesterol granuloma of the maxillary sinus in association with a dental implant—A case report

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Abstract

Background

Cholesterol granuloma is typically a benign granulomatous growth seen mostly in the mastoid process and the petrous temporal bone. Although cholesterol granuloma in maxillary sinus was first reported in the scientific literature in 1978, the occurrence is very rare and it is usually clinically and radiographically manifested ambiguously as maxillary sinusitis.

Purpose

The presence of cholesterol granuloma in the maxillary sinus in association with a dental pathology or prosthesis has been scarcely known. In this case report, we present a case of cholesterol granuloma in the maxillary sinus of a middle-aged male who had previously undergone dental implant placement in relation to that anatomical location.

Materials and Methods

A 64-year-old man reported to the Dental OP with a chief complaint of oral malodor, swelling, and tenderness over the right middle third of the face for the past 3 months. A cone beam computed tomography scan showed a well-defined radio-opaque lesion along with sclerosis and thinning of bone within the right maxillary antrum in relation to the dental implant placed in the 16 regions. The left maxillary sinus appeared normal. The Caldwell-Luc procedure was performed and a solitary soft lesion with yellowish-gray contents was evident within the right maxillary sinus. Histopathological examination revealed cholesterol clefts surrounded by foreign body giant cell reaction and granulation tissue formation, along with the presence of old and recent hemorrhage. A final diagnosis of cholesterol granuloma was made based on the histopathological examination report.

Conclusion

Based on the evidence available in the present case, we hypothesize that the localized trauma and hemorrhage initiated by implant placement in this particular anatomical location could have plausibly resulted in the occurrence of cholesterol granuloma in our patient.

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Τρίτη 18 Οκτωβρίου 2022

Adoption of adjuvant chemotherapy in high‐risk salivary gland malignancies

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Abstract

Background

The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies.

Methods

The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004–2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan–Meier and Cox proportional hazards analyses.

Results

Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan–Meier analysis (HR: 0.98; 95% CI: 0.86–1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78–1.09; p = 0.34).

Conclusions

Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

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Tamoxifen Alters TGF‐β1/Smad Signaling in Vocal Fold Injury

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Tamoxifen Alters TGF-β1/Smad Signaling in Vocal Fold Injury

This study investigated the effects of tamoxifen on acute vocal fold injury in a preclinical model. The antifibrotic actions of tamoxifen appear to be mediated by transforming growth factor beta 1/Smad signaling providing a novel target for intervention.


Objectives

Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF-β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis.

Methods

In vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF-β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real-time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre-injury day 5 to post-injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture.

Results

TAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF-β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF-β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment.

Conclusions

TAM has antifibrotic potential via the regulation of TGF-β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis.

Level of Evidence

NA Laryngoscope, 2022

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Early maladaptive schemas and ICD‐11 CPTSD symptoms: Treatment considerations

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Abstract

Objectives

Early maladaptive schemas (EMS) can result from adverse interpersonal traumatic experiences. The ICD-11 updated the concept of disorders following traumatic experiences with the new disorder of complex post-traumatic stress disorder (CPTSD). There is now a need to develop and test interventions for CPTSD. An essential step in identifying interventions that are particularly relevant to the treatment of CPTSD is to explore psychological constructs associated more closely with CPTSD compared to PTSD. The current study explored the associations of EMS with PTSD and CPTSD.

Design

The sample consisted of 603 adults (mean age = 41.65, SD = 13.8), recruited through social media and e-mails, and who responded to an online questionnaire.

Methods

Participants completed measures of demographic, traumatic life events, EMS, PTSD and CPTSD symptoms.

Results

Overall, results suggest that participants with CPTSD present with higher schema elevations across all schemas compared to those with PTSD or no diagnosis. Secondly, the schemas of emotional deprivation, abandonment/instability, social isolation/alienation, defectiveness/shame, enmeshment/undeveloped self, subjugation, emotional inhibition and insufficient self-control/self-discipline were significantly associated with the symptom clusters of CPTSD. Finally, results indicate that different schemas form significant associations with the individual symptom clusters of CPTSD.

Conclusions

Although results require replication in clinical samples, initial findings suggest that specific EMS may be important psychological correlates of CPTSD symptoms. Wider treatment considerations of these findings are discussed.

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Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis in Denmark: A Bayesian Hierarchical Analysis

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imageBackground: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. Methods: In this population-based case–control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989–2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NOx), carbon monoxide (CO), and fine particles (PM2.5) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NOx, CO). Results: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m3) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = –1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NOx (SD = 20 µg/m3) (–4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m3) (–3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM2.5) (SD = 2.37 µg/m3) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. Conclusions: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis.
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Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM2.5 Transition Metals and Oxidative Potential

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imageBackground: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O3 and NO2) and fine particulate air pollution (PM2.5). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM2.5 is more capable of causing oxidative stress. Methods: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM2.5 components and oxidative potential. Ox exposures (i.e., the redox-weighted average of O3 and NO2) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average Ox and mortality outcomes across strata of transition metals and sulfur in PM2.5 and three measures of PM2.5 oxidative potential adjusting for possible confounding factors. Results: Associations between Ox and mortality were consistently stronger in regions with elevated PM2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in Ox was associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OPGSH) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OPGSH levels below the median (interaction P value
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Δευτέρα 17 Οκτωβρίου 2022

Laryngopharyngeal Symptoms and Esophageal Disorder: The Role of Heterotopic Gastric Mucosa in Upper Esophagus

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Abstract

Background

Heterotopic gastric mucosa in the upper esophagus (HGMUE) was considered as geneogenous manifestation. However, its clinical characteristics may beyond to our knowledge if we focus on its extra-esophageal presentation. So the aim of this study was to investigate the relationship between HGMUE and laryngopharyngeal symptoms.

Method

Eight hundred and eleven patients who had gastric endoscopy examination were enrolled in this study and the cervical esophagus was examined for the patch during withdrawal of the endoscope. Questionnaire for gastroesophageal reflux disease (GERD-Q) and Reflux Symptom Index (RSI) were completed by all the patients. Pathology feature and therapeutic effect of HGMUE patients were evaluated.

Result

About 34.53% of the patients undergoing the gastroduodenoscopy had laryngopharyngeal (LP) symptoms. The relevance rate of HGMUE in LP(+)group(10.69%) was higher than that in LP(-) group(2%). The LP symptoms were related to the histological type and expression of H+-K+-ATPase in the histological sample of HGMUE patients. The positive rate of H+-K+-ATPase was 100% in LP(+) group, and that in LP(-) group was 28.6%. PPI therapy was effective for improving the LP symptoms in HGMUE patients. The RSI score in LP(+) patients decreased from 8.12±1.46 at baseline to 4±0.74 at the end of 8 weeks after treatment of PPI.

Conclusion

HGMUE was an important cause of LP symptoms in patients, especially in those who had no evidence of GERD. The mechanism of HGMUE induced LP symptoms was due to its location and the function of acid secretion according to the endoscopic finding and histologic characteristics.

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Κυριακή 16 Οκτωβρίου 2022

Characterization and application of a series of monoclonal antibodies against SARS‐CoV‐2 nucleocapsid protein

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Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic has a significant global social and economic impact, and the emergence of new and more destructive mutant strains highlights the need for accurate virus detection. Here, 90 monoclonal antibodies (MAbs) that exclusively reacted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (NP) were generated. These MAbs did not cross-react with NPs of common human coronaviruses (HCoV, i.e., 229E, OC43, HKU1, and NL63) and Middle East Respiratory Syndrome Coronavirus. Subsequently, overlapped peptides in individual fragments (N1–N4) of NP were synthesized. N1-3 (25-GSNQNGERSGARSKQ-39), N3-1 (217-AALALLLLDRLNQL-230), and N4-8 (393-TLLPAADLDDFSKQL-407) were identified as major epitopes using enzyme-linked immunoassay (ELISA) and recognized by 47, 1, and 18 MAbs, respectively. The 24 remaining MAbs exhibited no reactivity with all synthetic peptides. Among MAb-epitope pairs, only MAbs targeting epitope N1-3 displayed no cross-reaction with NPs of SARS-CoV-1 and other SARS-related CoVs. All omicron variants contained a three-amino acid deletion (31ERS33) in the N1-3 region. Thus, MAbs targeting N1-3 failed to recognize these variants. Furthermore, a double-antibody sandwich ELISA for antigen detection was established using the optimal MAbs. Overall, a series of MAbs targeting SARS-CoV-2 NP was prepared, characterized with epitope mapping, and applied for the detection of SARS-CoV-2 antigens, and some novel B-cell epitopes of the viral NP were identified.

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