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Regulatory Toxicology and Pharmacology... Oct 2023Propylene dichloride (PDC) is a chlorinated substance used primarily as an intermediate in basic organic chemical manufacturing. The United States Environmental... (Review)
Review
Propylene dichloride (PDC) is a chlorinated substance used primarily as an intermediate in basic organic chemical manufacturing. The United States Environmental Protection Agency (EPA) is currently evaluating PDC as a high-priority substance under the Toxic Substances Control Act (TSCA). We conducted a systematic review of the non-cancer and cancer hazards of PDC using the EPA TSCA and Integrated Risk Information System (IRIS) frameworks. We identified 12 epidemiological, 16 toxicokinetic, 34 experimental animal, and 49 mechanistic studies. Point-of-contact respiratory effects are the most sensitive non-cancer effects after inhalation exposure, and PDC is neither a reproductive nor a developmental toxicant. PDC is not mutagenic in vivo, and while in vitro evidence is mixed, DNA strand breaks consistently occur. Nasal tumors in rats and lung tumors in mice occurred after lifetime high-level inhalation exposure. Cholangiocarcinoma (CCA) was observed in Japanese print workers exposed to high concentrations of PDC. However, co-exposures, as well as liver parasites, hepatitis, and other risk factors, may also have contributed. The cancer mode of action (MOA) analysis revealed that PDC may act through multiple biological pathways occurring sequentially and/or simultaneously, although chronic tissue damage and inflammation likely dominate. Critically, health benchmarks protective of non-cancer effects are expected to protect against cancer in humans.
PubMed: 37562533
DOI: 10.1016/j.yrtph.2023.105468 -
Drugs in R&D Sep 2023At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.
METHODS
The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.
RESULTS
There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).
CONCLUSION
A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
Topics: Humans; Cardiomyopathy, Dilated; Carvedilol; Ivabradine; Stroke Volume; Trimetazidine; Network Meta-Analysis; Ventricular Function, Left; Verapamil; Randomized Controlled Trials as Topic
PubMed: 37556093
DOI: 10.1007/s40268-023-00435-5 -
Genes Jul 2023On a planet experiencing constant human population growth, it is necessary to explore the anthropogenic effects on the genetic diversity of species, and specifically...
On a planet experiencing constant human population growth, it is necessary to explore the anthropogenic effects on the genetic diversity of species, and specifically invasive species. Using an analysis that integrates comparative phylogeography, urban landscape genetics, macrogenetics and a systematic review, we explore the worldwide genetic diversity of the human commensal and anthropogenic species and . Based on metadata obtained considering 35 selected studies related to observed heterozygosity, measured by nuclear molecular markers (microsatellites, Single Nucleotide Polymorphisms-SNPs-, restrictition site-associated DNA sequencing -RAD-Seq-), socioeconomic and mobility anthropogenic factors were used as predictors of genetic diversity of and , using the Gini index, principal component analysis and Random Forest Regression as analysis methodology. Population density was on average the best predictor of genetic diversity in the species analyzed, indicating that the species respond in a particular way to the characteristics present in urban environments because of a combination of life history characteristics and human-mediated migration and colonization processes. To create better management and control strategies for these rodents and their associated diseases, it is necessary to fill the existing information gap in urban landscape genetics studies with more metadata repositories, with emphasis on tropical and subtropical regions of the world.
Topics: Humans; Rats; Animals; Population Density; Phylogeography; Introduced Species; Microsatellite Repeats; Polymorphism, Single Nucleotide
PubMed: 37510346
DOI: 10.3390/genes14071442 -
Circulation. Genomic and Precision... Aug 20231p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor . Early studies...
BACKGROUND
1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor . Early studies suggest that deletion of may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of loss is unknown.
METHODS
This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific knockout mouse ( conditional knockout) was generated. Echocardiography was performed at 4 and 6 to 7 months. Histology staining and qPCR were performed at 7 months to assess fibrosis.
RESULTS
The retrospective cohort included 71 patients. Among individuals with deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with not deleted (=0.1). In the combined retrospective and systematic review cohort (n=134), deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%, =0.03). deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device (=0.04). Among those deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts (=0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female conditional knockout mice. Further, female conditional knockout mice demonstrate significantly elevated risk of mortality (=0.0003).
CONCLUSIONS
deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality. conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with deletion should be assessed for cardiac disease.
Topics: Animals; Female; Humans; Male; Mice; Cardiomyopathies; DNA-Binding Proteins; Fibrosis; Mice, Knockout; Multicenter Studies as Topic; Retrospective Studies; Transcription Factors
PubMed: 37395136
DOI: 10.1161/CIRCGEN.122.003912 -
Scientific African Sep 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable diagnostic tests for comprehending and controlling the epidemic by tracking the world population. Given how crucial it is to monitor and manage the pandemic, researchers have recently concentrated on creating quick detection techniques. Although PCR is still the preferred clinical diagnostic test, there is a pressing need for substitutes that are sufficiently rapid and cost-effective to provide a diagnosis at the time of use. The creation of a quick and simple POC equipment is necessary for home testing. Our review's goal is to provide an overview of the many methods utilized to identify SARS-CoV 2 in various samples utilizing portable devices, as well as any potential applications for smartphones in epidemiological research and detection. The point of care (POC) employs a range of microfluidic biosensors based on smartphones, including molecular sensors, immunological biosensors, hybrid biosensors, and imaging biosensors. For example, a number of tools have been created for the diagnosis of COVID-19, based on various theories. Integrated portable devices can be created using loop-mediated isothermal amplification, which combines isothermal amplification methods with colorimetric detection. Electrochemical approaches have been regarded as a potential substitute for optical sensing techniques that utilize fluorescence for detection and as being more beneficial to the Minimizing and simplicity of the tools used for detection, together with techniques that can amplify DNA or RNA under constant temperature conditions, without the need for repeated heating and cooling cycles. Many research have used smartphones for virus detection and data visualization, making these techniques more user-friendly and broadly distributed throughout nations. Overall, our research provides a review of different novel, non-invasive, affordable, and efficient methods for identifying COVID-19 contagious infected people and halting the disease's transmission.
PubMed: 37351482
DOI: 10.1016/j.sciaf.2023.e01757 -
Biomarkers : Biochemical Indicators of... Dec 2023Circulating tumour DNA (ctDNA) has demonstrated robust diagnostic accuracy in several digestive cancers. However, the prognostic role of ctCDNA in gastric cancer (GC)... (Meta-Analysis)
Meta-Analysis
Circulating tumour DNA (ctDNA) has demonstrated robust diagnostic accuracy in several digestive cancers. However, the prognostic role of ctCDNA in gastric cancer (GC) is still controversial. This systematic review and meta-analysis aimed to evaluate the prognostic value of ctDNA in GC. PubMed, Web of Science and Cochrane databases were searched to identify studies reporting the use of ctDNA to predict GC outcome and all relevant studies published until November 2022 were enrolled for our analysis. Data were extracted by two authors independently and statistic analysis was conducted by R program with 'meta' and 'metafor' packages. A total of 34 qualified articles with 5091 subjects were incorporated into our meta-analysis. The corresponding Hazard ratio (HR) of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 2.74 (95% CI:2.24-3.35), 3.13 (95% CI:2.08-4.72) and 3.04 (95% CI:2.46-3.76), respectively, in GC patients. Blood-based ctDNA assay would be a potential novel biomarker for GC evaluation and prediction. This is the integrated meta-analysis on the association of circulating tumour DNA (ctDNA) and prognosis of gastric cancer (GC) with an increasing number of studies exploring the prognostic value of GC in the last few years, which depicted that the detection of ctDNA could be a promising predictor in GC patients.
Topics: Humans; Prognosis; Circulating Tumor DNA; Stomach Neoplasms; Biomarkers, Tumor; Disease-Free Survival
PubMed: 37036017
DOI: 10.1080/1354750X.2023.2201664 -
European Journal of Neurology Nov 2023The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous.... (Review)
Review
BACKGROUND AND PURPOSE
The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous. These discrepancies arise not only from the highly heterogeneous pathology of PD, but also from widely varying methodologies at all stages of the workflow, from sampling to final statistical analysis. The aim of the present work is to harmonize the workflow across studies to reduce the methodological heterogeneity and to perform a pooled analysis to account for other sources of heterogeneity.
METHODS
We performed a systematic review to identify studies comparing the gut microbiota of PD patients to healthy controls. A workflow was designed to harmonize processing across all studies from bioinformatics processing to final statistical analysis using a Bayesian random-effects meta-analysis based on individual patient-level data.
RESULTS
The results show that harmonizing workflows minimizes differences between statistical methods and reveals only a small set of taxa being associated with the pathogenesis of PD. Increased shares of the genera Akkermansia and Bifidobacterium and decreased shares of the genera Roseburia and Faecalibacterium were most characteristic for PD-associated microbiota.
CONCLUSIONS
Our study summarizes evidence that reduced levels of butyrate-producing taxa in combination with possible degradation of the mucus layer by Akkermansia may promote intestinal inflammation and reduced permeability of the gut mucosal layer. This may allow potentially pathogenic metabolites to transit and enter the enteric nervous system.
PubMed: 36593694
DOI: 10.1111/ene.15671