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Consequently, this paper demonstrates for the first time that the cumulative SMF exposure promoted the self-renewal ability of OSCs via autophagic degradation of ferritin, implying that ferritinophagy may be a potential molecular target for cancer. © 2021 Bioelectromagnetics Society.Rare variants of the olfactomedin domain of myocilin are considered causative for inherited, early-onset open-angle glaucoma, with a misfolding toxic gain-of-function pathogenic mechanism detailed by 20 years of laboratory research. Myocilin variants are documented in the scientific literature and identified through large-scale genetic sequencing projects such as those curated in the Genome Aggregation Database (gnomAD). In the absence of key clinical and laboratory information, however, the pathogenicity of any given variant is not clear, because glaucoma is a heterogeneous and prevalent age-onset disease, and common variants are likely benign. In this review, we reevaluate the likelihood of pathogenicity for the ~100 nonsynonymous missense, insertion-deletion, and premature termination of myocilin olfactomedin variants documented in the literature. We integrate available clinical, laboratory cellular, biochemical and biophysical data, the olfactomedin domain structure, and population genetics data from gnomAD. Of the variants inspected, ~50% can be binned based on a preponderance of data, leaving many of uncertain pathogenicity that motivate additional studies. Ultimately, the approach of combining metrics from different disciplines will likely resolve outstanding complexities regarding the role of this misfolding-prone protein within the context of a multifactorial and prevalent ocular disease, and pave the way for new precision medicine therapeutics.
This systematic review aims to identify disease-specific and generic quality of life (QoL) outcome measurement instruments used in populations of women with urinary incontinence (UI) and to determine the most psychometrically robust and appropriate disease-specific and generic tools for measuring the quality of life in this population.
A systematic search was conducted of PubMed, Embase, SCIELO, and CINAHL databases for studies evaluating measurement properties of QoL instruments in women with UI. The methodological quality of studies and the quality of measurement properties were evaluated using the COnsensus-based Standards for the selection of health status Measurement INtruments (COSMIN) checklist and quality criteria. Overall, evidence for measurement properties was graded using the modified grading of recommendations, assessment, development & evaluation approach.
A total of 73 studies were included, and 27 specific and 6 generic instruments were identified. The Incontinence QoL questionnaire (IQoL) had the highest overall psychometric quality for English-speaking populations and was the most widely translated tool. Evidence for generic QoL tools in this population is limited. Few studies evaluated measurement error or cross-cultural validity.
The IQoL is the most psychometrically robust disease-specific tool for use in this population. More research is needed to determine the most psychometrically robust generic tool. Future studies should also evaluate measurement error and cross-cultural validity as evidence for these properties is particularly lacking.
The IQoL is the most psychometrically robust disease-specific tool for use in this population. More research is needed to determine the most psychometrically robust generic tool. Future studies should also evaluate measurement error and cross-cultural validity as evidence for these properties is particularly lacking.Interest in analyzing X chromosome single nucleotide polymorphisms (SNPs) is growing and several approaches have been proposed. Prior studies have compared power of different approaches, but bias and interpretation of coefficients have received less attention. We performed simulations to demonstrate the impact of X chromosome model assumptions on effect estimates. We investigated the coefficient biases of SNP and sex effects with commonly used models for X chromosome SNPs, including models with and without assumptions of X chromosome inactivation (XCI), and with and without SNP-sex interaction terms. Sex and SNP coefficient biases were observed when assumptions made about XCI and sex differences in SNP effect in the analysis model were inconsistent with the data-generating model. However, including a SNP-sex interaction term often eliminated these biases. To illustrate these findings, estimates under different genetic model assumptions are compared and interpreted in a real data example. Models to analyze X chromosome SNPs make assumptions beyond those made in autosomal variant analysis. Assumptions made about X chromosome SNP effects should be stated clearly when reporting and interpreting X chromosome associations. Fitting models with SNP × Sex interaction terms can avoid reliance on assumptions, eliminating coefficient bias even in the absence of sex differences in SNP effect.
Lower urinary tract symptoms are common in multiple sclerosis (MS) and have a great impact on quality of life. We evaluated prevalence and characteristics of urological symptoms in a cohort of patients with MS.
This is a cross-sectional study conducted on consecutive patients with MS attending our Center in 2018. We evaluated prevalence, clinical features, and response to symptomatic treatments of lower urinary tract disorders; we investigated the relationship between them and clinical and demographic features. Data of urodynamic studies were also collected.
In our cohort of 806 patients, the overall prevalence of urological symptoms was 52.9% and urgency was the most frequent symptom (59.4%). Symptomatic patients had a higher disability, a longer disease duration, a later age at onset, and a greater mean age at the time of evaluation. Urinary disorders were more frequent in patients with progressive disease and in women. About 41.8% of patients were under treatment for the urological disorder and 81.5% of them reported an improvement of symptoms.
Urinary disorders in patients with MS have a high prevalence. An early and correct characterization of types of symptoms and an early and targeted therapeutic strategy are essential to improve the patient's quality of life and avoid future complications.
Urinary disorders in patients with MS have a high prevalence. An early and correct characterization of types of symptoms and an early and targeted therapeutic strategy are essential to improve the patient's quality of life and avoid future complications.
Patient-reported pad-count as continence rate assessment tool after artificial urinary sphincter (AUS) implantation is common. However, lack of standardized continence definition using this method results in heterogeneous published efficacy outcomes. Data on 24-h pad weight tests (PWT) after primary AUS implantation for postprostatectomy urinary incontinence (PPUI) is scarce. Our aim was to evaluate the 24-h PWT as an efficacy assessment tool and correlate it to qualitative outcomes using validated questionnaires.
This retrospective, single center, follow-up cohort study, evaluated 180 patients who underwent primary AUS implantation for PPUI from 2005 to 2018. Voiding diaries, 24-h PWT, validated patient satisfaction and quality of life (QoL) questionnaires were collected pre-operatively and at 3-6 months postactivation, using the institution's Electronic Medical Records.
The median preoperative and postoperative 24-h PWT values were 494 (interquartile range [IQR] 304-780) and 7 (IQR 0-25) g respectively with a significant improvement in urinary leakage of 489.5 g 99.1% (p < 0.001). Median preoperative and postoperative I-QoL results increased from 33.5 (IQR 19.3-63.6) to 86.4 (IQR 73.9-94.3) points, with a significant 52.9 points improvement in QoL (p < 0.001). Similarly, the median preoperative and postoperative ICIQ-SF values decreased from 20 (IQR 17-21) to 5 (IQR 3-9) points, showing a significant improvement of 15 points (p < 0.001). We also found a significant correlation between PWT and patient satisfaction.
The 24-h PWT provides a reliable and objective assessment of continence rates, with a strong correlation to qualitative outcomes, after primary AUS implantation for PPUI. Its use could help reduce reported outcome heterogeneity across studies.
The 24-h PWT provides a reliable and objective assessment of continence rates, with a strong correlation to qualitative outcomes, after primary AUS implantation for PPUI. Its use could help reduce reported outcome heterogeneity across studies.Multitrait tests can improve power to detect associations between individual single-nucleotide polymorphisms (SNPs) and several related traits. Here, we develop methods for multi-SNP transcriptome-wide association (TWAS) tests to test the association between predicted gene expression levels and multiple phenotypes. We show that the correlation in TWAS test statistics for multiple phenotypes has the same form as multitrait statistics for the single-SNP setting. Thus, established methods for combining single-SNP test statistics across multiple traits can be extended directly to the TWAS setting. We performed an extensive evaluation across eight multitrait methods in simulations that varied gene-phenotype effect sizes in addition to the underlying covariance structure among the phenotypes. We found that all multitrait TWAS tests have well-calibrated Type I error (except ASSET, which can have a slightly elevated or depressed Type I error rate). buy Savolitinib Our results show that multitrait TWAS can improve statistical power compared with multiple single-trait TWAS followed by Bonferroni correction. To illustrate our approach to real data, we conducted a multitrait TWAS of four circulating lipid traits from the Global Lipids Genetics Consortium. We found that our multitrait Wald TWAS approach identified 506 genes associated with lipid levels compared with 87 identified through Bonferroni-corrected single-trait TWAS. Overall, we find that our proposed multitrait TWAS framework outperforms single-trait approaches to identify new genetic associations, especially for functionally correlated phenotypes and phenotypes with overlapping genome-wide association studies samples, leading to insights into the genetic architecture of multiple phenotypes.
To evaluate the efficacy and safety of fractional 1064 nm NdYAG picosecond laser combined with intense pulsed light (IPL) in the treatment of atrophic acne scar with post-inflammatory erythema (PIE). © 2021 Wiley Periodicals LLC.
Seventeen patients received five sessions of treatment at weeks 0, 4, 8, 12, 16 and were followed up at week 28. One half of the face was randomly treated by fractional 1064 nm NdYAG picosecond laser combined with IPL (FxPico + IPL), and the other by IPL alone as a control.
For the 15 patients who completed the study, the FxPico + IPL side demonstrated significant median Échelle D'évaluation clinique des cicatrices D'acné (ECCA) score improvement (P < 0.01), while IPL alone side did not (P = 0.1250). The pore counts for both sides decreased but more pore count reduction was seen on the FxPico + IPL side (P < 0.05). Better scar improvement was observed on the FxPico + IPL-treated side (P < 0.05) while no difference in erythema improvement was seen between the two sides.
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