Αρχειοθήκη ιστολογίου

Τρίτη 18 Οκτωβρίου 2022

Hypermethylation of RASSF1A gene in pediatric rhabdoid tumor of the kidney and clear cell sarcoma of the kidney

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Abstract

Background

Among pediatric renal tumors, rhabdoid tumor of the kidney (RTK) and clear cell sarcoma of the kidney (CCSK) are rare and associated with an unfavorable prognosis, while congenital mesoblastic nephroma (CMN) is associated with a good prognosis. Methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) promoter has been reported to correlate with a poor prognosis in patients with Wilms tumors, while its methylation status is unclear in other types of pediatric renal tumors.

Method

DNA methylation of the RASSF1A promoter in several pediatric renal tumors was analyzed with pyrosequencing. In order to clarify the correlation between expression of RASSF1A and DNA methylation of its promoter, the RTK cell line was treated with 5-Aza-2′-deoxycytidine (5-Aza-dC). RASSF1A was overexpressed in the RTK cell line to evaluate its functional effects.

Results

Quantitative methylation analysis demonstrated hypermethylation in the RASSF1A promoter region in RTK and CCSK, but not CMN. The 5-Aza-dC treatment induced demethylation of the RASSF1A promoter as well as increased RASSF1A mRNA expression. The transduction of RASSF1A has an effect on the suppression of viability and proliferation of RTK cells.

Conclusion

DNA methylation-mediated deficiency of RASSF1A might be involved in the development and aggressiveness of some pediatric renal tumors and correlated with a poor prognosis.

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Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham)

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Abstract

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.

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Posterior nasal neurectomy for intractable rhinitis: a systematic review of the literature

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Abstract

Background

Rhinitis affects up to 40% of the population worldwide and can significantly reduce quality of life. Some patients remain symptomatic despite maximal medical therapy. In refractory cases, posterior nasal neurectomy (PNN - the endoscopic division of the intranasal nerve branches containing postganglionic parasympathetic fibres) is postulated to reduce symptom burden.

Objectives of review

To establish whether PNN is effective and safe in the management of allergic and non-allergic rhinitis.

Type of review

Systematic review

Methods

A comprehensive literature search was undertaken using PubMed, EMBASE, MEDLINE, and Cochrane. The inclusion criteria were: studies published in English, studies where PNN was performed either with or without additional procedures, and where measures of objective/subjective outcomes and/or complications were reported. Extracted data included study type, sample size, surgical technique, study population characteristics, follow-up period, outcome measures, complications of surgery, and symptom outcomes.

Results

Twenty-three articles satisfied the inclusion criteria studying in total 2282 patients. Sample size ranged from 8-1056. There were three randomised controlled trials, three case control studies, and the remaining seventeen were case series using both objective and subjective outcome measures. All but one study found improved patient reported outcomes following PNN. Complications were reported in 14 studies - epistaxis was the most common complication and was observed in 30 patients (1.5% of subjects).

Conclusions

Posterior nasal neurectomy had a low rate of complications. Although most studies reported significant symptomatic improvement, their heterogeneity, level of evidence, study design, and/or quality was not sufficient to draw any firm conclusions on the effectiveness of the procedure. Larger, well designed studies are needed to clarify its role in the management of difficult-to-treat rhinitis.

This article is protected by copyright. All rights reserved.

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The Role of Pelvic Floor Muscle Training on Low Anterior Resection Syndrome: A Multicenter Randomized Controlled Trial

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imageBackground and Objective: Total mesorectal excision (TME) for rectal cancer (RC) often results in significant bowel symptoms, commonly known as low anterior resection syndrome (LARS). Although pelvic floor muscle training (PFMT) is recommended in noncancer populations for treating bowel symptoms, this has been scarcely investigated in RC patients. The objective was to investigate PFMT effectiveness on LARS in patients after TME for RC. Methods: A multicenter, single-blind prospective randomized controlled trial comparing PFMT (intervention; n=50) versus no PFMT (control; n=54) 1 month following TME/stoma closure was performed. The primary endpoint was the proportion of participants with an improvement in the LARS category at 4 months. Secondary outcomes were: continuous LARS scores, ColoRectal Functioning Outcome scores, Numeric Rating Scale scores, stool diary items, and Short Form 12 scores; all assessed at 1, 4, 6, and 12 months. Results: The proportion of participants with an improvement in LARS category was statistically higher after PFMT compared with controls at 4 months (38.3% vs 19.6%; P=0.0415) and 6 months (47.8% vs 21.3%; P=0.0091), but no longer at 12 months (40.0% vs 34.9%; P=0.3897). Following secondary outcomes were significantly lower at 4 months: LARS scores (continuous, P=0.0496), ColoRectal Functioning Outcome scores (P=0.0369) and frequency of bowel movements (P=0.0277), solid stool leakage (day, P=0.0241; night, P=0.0496) and the number of clusters (P=0.0369), derived from the stool diary. No significant differences were found for the Numeric Rating Scale/quality of life scores. Conclusions: PFMT for bowel symptoms after TME resulted in lower proportions and faster recovery of bowel symptoms up to 6 months after surgery/stoma closure, justifying PFMT as an early, first-line treatment option for bowel symptoms after RC.
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Mobile Health Application and Hypertension Management in Rural, Middle-Aged Adults: A Quality Improvement Project

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imageOver 29% of the adult population in the United States are diagnosed with hypertension, and rates are significantly higher in those adults who live in rural areas. Hypertension is recognized as the most prevalent comorbidity and modifiable risk factor leading to premature death. The purpose of this quality improvement project was to determine if using a mobile phone–based health application called Medisafe could enhance medication adherence and improve blood pressure control in rural-dwelling adults. A small group (N = 14) of middle-aged (45-64 years old) patients with hypertension were recruited to download the free Medisafe phone-based health application. Patients utilized the Medisafe application between their initial visit and a 4- to 6-week follow-up. At the follow-up visit, 64% (n = 9) of participants improved their level of hypertension control by blood pressure classification and improved their scores on the medication adherence questionnaire. The findings from this quality improvement project suggest the Medisafe application is useful to enhance medication adherence and blood pressure control. Future research and quality improvement initiatives are necessary to determine the broader efficacy of phone-based health applications in the rural adult population.
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Factors Considered Important by Healthcare Professionals for the Management of Using Complementary Therapy in Diabetes: A Text-Mining Analysis

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imageText-mining algorithms can identify the most prevalent factors of risk-benefit assessment on the use of complementary and integrative health approaches that are found in healthcare professionals' written notes. The aims of this study were to discover the key factors of decision-making on patients' complementary and integrative health use by healthcare professionals and to build a consensus-derived decision algorithm on the benefit-risk assessment of complementary and integrative health use in diabetes. The retrospective study of an archival dataset used a text-mining method designed to extract and analyze unstructured textual data from healthcare professionals' responses. The techniques of classification, clustering, and extraction were performed with 1398 unstructured clinical notes made by healthcare professionals between 2019 and 2020. The most important factor for decision-making by healthcare professionals about complementary and integrative health use in patients with diabetes was the ingredients of the product. Other important factors were the patient's diabetes control, the undesirable effects from complementary and integrative health, evidence-based complementary and integrative health, medical laboratory data, and the product's affordability. This exploratory text-mining study provides insight into how healthcare professionals decide complementary and integrative health use for patients with diabetes after a risk-benefit assessment from clinical narrative notes.
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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

Bioactivity analysis of bioceramic sealers and repair cements on the phenotype and cytokine secretion profile of CD14+ monocytes: An ex‐vivo study

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Abstract

Aim

This study evaluated the immune bioactivity of testing media (TM) obtained from different calcium silicate-based sealers and cements on monocyte morphology, activation, differentiation, and cytokine secretion.

Methods

Blood-derived CD14+ monocytes were isolated and cultured for 5 days with 25% TM from the following calcium silicate-based materials: TotalFill BC RRM Fast-Set Putty, Biodentine, TotalFill BC Sealer, and BioRoot-RCS. A resin-based endodontic cement was used as a control. The expression of surface markers such as CD86, HLA-DR, CD16, CD309, and CD209, and cytokine secretion were analysed by flow cytometry. Data were analysed using the one-way repeated measures (RM) analysis of variance (ANOVA) multiple comparison test and a Holm-Sidak multiple comparison post-hoc test (p<0.05).

Results

This comparative analysis revealed that monocytes co-cultured with calcium silicate-based materials showed a spindle-shaped morphology compared to the round shape observed in the control. Regarding activation markers, BioRoot-RCS and Biodentine significantly increased CD86 expression compared with the control sample, whereas no significant differences (p>0.05) were observed in HLA-DR expression. In addition, no differences were observed among the differentiation markers. When the inflammatory cytokines were analysed, BioRoot-RCS increased the secretion of IL-1β, IL-6, IL-10, and TNF-α, whereas BioRoot-RCS and Biodentine significantly decreased IL-8 production (p<0.05).

Conclusions

These data showed that the calcium silicate-based materials tested changed the morphology of CD14+ monocytes; however, only BioRoot-RCS and Biodentine significantly upregulated CD86. In addition, BioRoot-RCS was the sealer with the highest immunomodulatory properties for cytokine production which means that it can contribute with the in vivo healing process and regeneration of periapical lesions.

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