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

alexandrossfakianakis shared this article with you from Inoreader Tamoxifen Alters TGF‐β1/Smad Signaling in Vocal Fold Injury via The Laryngoscope 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 View on Web

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Monkeypox treatment: current evidence and future perspectives

alexandrossfakianakis shared this article with you from Inoreader Monkeypox treatment: current evidence and future perspectives via Journal of Medical Virology Abstract As of 11 September 2022, 57,669 reports of monkeypox infection raised global concern. Previous vaccinia virus vaccination can protect from monkeypox. However, after smallpox eradication, immunization against that was stopped. Indeed, therapeutic options following the disease onset are of great value. This study aimed to review the available evidence on virology and treatment approaches for monkeypox and provide guidance for patient care and future studies. Since no randomized clinical trials were ever performed, we reviewed monkeypox animal model studies and clinical trials on the safety and pharmacokinetics of available medications. Brincidofovir and tecovirimat were the most studied medications that got approval for smallpox treatment according to the Animal Rule. Due to the conserved virology among orthopoxviruses, available medications might also be effective against monkeypox. However, tecovirimat has the strongest evidence to be effective and saf e for monkeypox treatment, and if there is a choice between the two drugs, tecovirimat has shown more promise so far. The risk of resistance should be considered in patients who failed to respond to tecovirimat. Hence, the target-based design of novel antivirals will enhance the availability and spectrum of effective anti-orthopoxvirus agents. This article is protected by copyright. All rights reserved. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Hypermethylation of RASSF1A gene in pediatric rhabdoid tumor of the kidney and clear cell sarcoma of the kidney via Pediatric Blood & Cancer 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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham) via Pediatric Blood & Cancer 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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Posterior nasal neurectomy for intractable rhinitis: a systematic review of the literature via Clinical Otolaryngology 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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader The Role of Pelvic Floor Muscle Training on Low Anterior Resection Syndrome: A Multicenter Randomized Controlled Trial via Annals of Surgery - Most Popular Articles Background 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. View on Web

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Mobile Health Application and Hypertension Management in Rural, Middle-Aged Adults: A Quality Improvement Project

alexandrossfakianakis shared this article with you from Inoreader Mobile Health Application and Hypertension Management in Rural, Middle-Aged Adults: A Quality Improvement Project via Computers Informatics Nursing - Published Ahead-of-Print Over 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. View on Web

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Factors Considered Important by Healthcare Professionals for the Management of Using Complementary Therapy in Diabetes: A Text-Mining Analysis

alexandrossfakianakis shared this article with you from Inoreader Factors Considered Important by Healthcare Professionals for the Management of Using Complementary Therapy in Diabetes: A Text-Mining Analysis via Computers Informatics Nursing - Published Ahead-of-Print Text-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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis in Denmark: A Bayesian Hierarchical Analysis via Epidemiology - Current Issue Background: 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. View on Web

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Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM2.5 Transition Metals and Oxidative Potential

alexandrossfakianakis shared this article with you from Inoreader Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM2.5 Transition Metals and Oxidative Potential via Epidemiology - Current Issue Background: 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 View on Web

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