Interrater Reliability of the Wolf Motor Function Test–Functional Ability Scale: Why It Matters

Background. One important objective for clinical trialists in rehabilitation is determining efficacy of interventions to enhance motor behavior. In part, limitation in the precision of measurement presents a challenge. The few valid, low-cost observational tools available to assess motor behavior cannot escape the variability inherent in test administration and scoring. This is especially true when there are multiple evaluators and raters, as in the case of multisite randomized controlled trials (RCTs). One way to enhance reliability and reduce variability is to implement rigorous quality control (QC) procedures. Objective. This article describes a systematic QC process used to refine the administration and scoring procedures for the Wolf Motor Function Test (WMFT)–Functional Ability Scale (FAS). Methods. The QC process, a systematic focus-group collaboration, was developed and used for a phase III RCT, which enlisted multiple evaluators and an experienced WMFT-FAS rater panel. Results. After 3 staged refinements to the administration and scoring instructions, we achieved a sufficiently high interrater reliability (weighted κ = 0.8). Conclusions and Implications. A systematic focus-group process was shown to be an effective method to improve reliability of observational assessment tools for motor behavior in neurorehabilitation. A reduction in noise-related variability in performance assessments will increase power and potentially lower the number needed to treat. Improved precision of measurement can lead to more cost-effective and efficient clinical trials. Finally, we suggest that improved precision in measures of motor behavior may provide more insight into recovery mechanisms than a single measure of movement time alone

Disaster experience and resident risk preference: Evidence from China household finance survey.

China is one of the countries hardest hit by disasters. Disaster shocks not only cause a large number of casualties and property damage but also have an impact on the risk preference of those who experience it. Current research has not reached a consensus conclusion on the impact of risk preferences. This paper empirically analyzes the effects of natural and man-made disasters on residents' risk preference based on the data of the China Household Financial Survey (CHFS) in 2019. The results indicate that: (1) Both natural and man-made disasters can significantly lead to an increase in the risk aversion of residents, and man-made disasters have a greater impact. (2) Education background plays a negative moderating role in the impact of man-made disasters on residents' risk preference. (3) Natural disaster experiences have a greater impact on the risk preference of rural residents, while man-made disaster experiences have a greater impact on the risk preference of urban residents. Natural disaster experiences make rural residents more risk-averse, while man-made disaster experiences make urban residents more risk-averse. The results provide new evidence and perspective on the negative impact of disaster shocks on the social life of residents

HPV genotypic spectrum in Jilin province, China, where non-vaccine-covered HPV53 and 51 are prevalent, exhibits a bimodal age-specific pattern.

BACKGROUND:Human papillomavirus (HPV), the most common sexually transmitted disease, is involved in a series of other diseases. The persistent infection of high-risk HPVs (HR-HPVs) is considered to be the causative agent of cervical cancer, and it is related to noncervical cancers. The present study aims to estimate the HPV prevalence and genotype distribution in Jilin province, China, to guide HPV-related cervical cancer screening and HPV vaccination. METHODS:From October 2017 to September 2019, 21,282 samples (634 male and 20,648 female) were collected for HPV infection detection using an HPV genotyping panel. The age-related HPV prevalence and morbidity of HPV-based disease and HPV prevalence associated with specific diseases were analyzed. RESULTS:A total of 7095 (34.4%) positive for HPV infection of 20648 women, and 164 (25.8%) positive of 634 men. The HPV prevalence among women exhibited a bimodal pattern, with a peak in young group and a second peak in old group, with increased severity of cervical lesions. HPV16 (7.8%), HPV52 (5.8%), HPV58 (5.0%), HPV53 (3.4%), and HPV51 (3.0%) were the most prevalent genotypes among women, and HPV6 (6.0%), HPV11 (5.7%), HPV16 (3.6%), HPV18 (2.7%), and HPV51 (3.0%) were prevalent among men. Non-vaccine-covered HPV53 and 51 were found in 6.3% of HPV infection and 8.9% of cervical cancer in Jilin province. Furthermore, 45.5% of females and 28.6% of males with genital warts were infected with HR-HPV genotypes. CONCLUSION:The HPV genotypic spectrum in Jilin province, where non-vaccine-covered HPV53 and 51 were prevalent, exhibited an age- and cervical lesion-specific pattern, which provides guidance for HPV vaccination and cervical cancer screening. HPV infection in men and benign hyper-proliferative lesions should not be neglected

Publisher Correction: Nucleation-controlled growth of superior lead-free perovskite Cs3Bi2I9 single-crystals for high-performance X-ray detection

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Activation of the p62-Keap1-Nrf2 pathway protects against oxidative stress and excessive autophagy in ovarian granulosa cells to attenuate DEHP-induced ovarian impairment in mice

Di-(2-ethylhexyl) phthalate (DEHP) is widely used in various plastics but has been demonstrated to cause female reproductive toxicity. However, the exact mechanism underlying the ovarian damage induced by DEHP remains unclear. In this study, DEHP was administered orally to 5-week-old female mice for 30 days at doses of 0, 250, 500, and 1000 mg/kg/day. The findings demonstrated that DEHP exposure disrupted ovarian function and follicular development as well as induced oxidative stress and autophagy in ovarian granulosa cells (GCs). Further, 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP in vivo, induced autophagy in both human ovarian granulosa cells line (KGN) and mouse primary GCs within 24 h in vitro. However, it did not affect the p62-dependent autophagy flux. Furthermore, MEHP-induced autophagy was inhibited by the autophagy inhibitor 3-MA and exacerbated by the autophagy activator rapamycin, indicating that MEHP induces excessive autophagy in GCs. Subsequently, we found that MEHP-induced autophagic cell death was primarily attributed to oxidative damage from elevated intracellular ROS levels. Meanwhile, MEHP exposure induced nuclear translocation of erythroid-derived factor 2-related factor (Nrf2), a key regulator of antioxidant activity resulting in activating antioxidant effects. Interestingly, we also found that MEHP-induced increase in p62 competitively binds Keap1, thereby facilitating nuclear translocation of Nrf2 and establishing a positive feedback loop in antioxidant regulation. Therefore, this study demonstrated that inhibition of Nrf2 could aggravate oxidative damage and enhance excessive autophagy caused by MEHP, while activation of Nrf2 could reverse the trend. These findings have also been reinforced in studies of cultured ovaries in vitro. Our study suggests that the p62-Keap1-Nrf2 pathway may serve as a potential protective mechanism against DEHP-induced oxidative stress and excessive autophagy in mouse GCs

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) alleviate excessive autophagy of ovarian granular cells through VEGFA/PI3K/AKT/mTOR pathway in premature ovarian failure rat model

Abstract Background Premature ovarian failure (POF) is one of the leading causes of female infertility and is accompanied by abnormal endocrine, seriously affecting female quality of life. Previous studies have demonstrated that mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for POF. However, the mechanism remains obscure. This study aims to investigate the therapeutic effect of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on ovarian function in the POF rat model and explore the underlying mechanisms. Methods The ovarian function was evaluated by ovarian morphology, histology, estrous cycle, hormone levels (AMH, E2, FSH, and LH), and fertility ability to investigate the effect of hUC-MSCs on the POF rats model. The cytokines levels were assayed in serum using protein array to explore the mechanisms of hUC-MSCs therapy for POF. The excessive autophagy levels were evaluated using a co-culture system of 3D MSCs spheroids with human ovarian granulosa cell line (KGN) or primary ovarian granulosa cells (GCs) to understand the paracrine effect of hUC-MSCs on GCs. The related proteins expression of autophagy and PI3K/AKT/mTOR pathway was detected using Western Blotting and/or in various inhibitors supplement to further demonstrate that vascular endothelial growth factor A (VEGFA) secreted by hUC-MSCs can alleviate excessive autophagy of ovarian GCs via PI3K/AKT/mTOR signaling pathway. The ovarian culture model in vitro was applied to confirm the mechanism. Results The ovarian function of POF and the excessive autophagy of ovarian GCs were restored after hUC-MSCs transplantation. The protein array result demonstrated that VEGF and PI3K/AKT might improve ovarian function. in vitro experiments demonstrated that VEGFA secreted by hUC-MSCs could decrease oxidative stress and inhibit excessive autophagy of ovarian GCs via PI3K/AKT/mTOR pathway. The ovarian culture model results confirmed this mechanism in vitro. Conclusion The hUC-MSCs can alleviate excessive autophagy of ovarian GCs via paracrine VEGFA and regulate the PI3K/AKT/mTOR signaling pathway, thereby improving the ovarian function of POF

The Two-Component Signal Transduction System ArlRS Regulates <em>Staphylococcus epidermidis</em> Biofilm Formation in an <em>ica</em>-Dependent Manner

<div><p>Due to its ability to form biofilms on medical devices, <em>Staphylococcus epidermidis</em> has emerged as a major pathogen of nosocomial infections. In this study, we investigated the role of the two-component signal transduction system ArlRS in regulating <em>S. epidermidis</em> biofilm formation. An ArlRS-deficient mutant, WW06, was constructed using <em>S. epidermidis</em> strain 1457 as a parental strain. Although the growth curve of WW06 was similar to that of SE1457, the mutant strain was unable to form biofilms <em>in vitro</em>. In a rabbit subcutaneous infection model, sterile disks made of polymeric materials were implanted subcutaneously followed with inoculation of WW06 or SE1457. The viable bacteria cells of WW06 recovered from biofilms on the embedded disks were much lower than that of SE1457. Complementation of arlRS genes expression from plasmid in WW06 restored biofilm-forming phenotype both <em>in vivo</em> and <em>in vitro</em>. WW06 maintained the ability to undergo initial attachment. Transcription levels of several genes involved in biofilm formation, including <em>icaADBC</em>, <em>sigB</em>, and <em>sarA</em>, were decreased in WW06, compared to SE1457; and <em>icaR</em> expression was increased in WW06, detected by real-time reverse-transcription PCR. The biofilm-forming phenotype was restored by overexpressing <em>icaADBC</em> in WW06 but not by overexpressing <em>sigB</em>, indicating that ArlRS regulates biofilm formation through the regulation of <em>icaADBC</em>. Gel shift assay showed that ArlR can bind to the promoter region of the <em>ica</em> operon. In conclusion, ArlRS regulates <em>S. epidermidis</em> biofilm formation in an <em>ica</em>-dependent manner, distinct from its role in <em>S. aureus</em>.</p> </div