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The exercise program is designed and carried out on a frequent basis within an extensive scheduled time aimed at improving functional performance, aerobic capacity, and healthy conditions. Finally, a combination of exercise training and therapeutic nutrition is powerfully recommended to control sarcopenia in cirrhosis.Epigenetic gene silencing by aberrant DNA methylation leads to loss of key cellular pathways in tumorigenesis. In order to analyze the effects of DNA methylation on prostate cancer, we established LNCaP-derived human prostate cancer cells that can pharmacologically induce global reactivation of hypermethylated genes by the methyl-CpG targeted transcriptional activation (MeTA) method. The MeTA suppressed the growth of LNCaP-derived cells and induced apoptosis. Microarray analysis indicated that PYCARD (PYD and CARD domain containing) encoding an apoptosis-inducing factor was upregulated by 65-fold or more after treatment with MeTA. We analyzed DNA methylation statuses using 50 microdissected primary prostate cancer tissues and found an extremely high frequency of tumor-specific promoter hypermethylation of PYCARD (90%, 45/50). Moreover, DNA methylation status was significantly associated with Gleason score (P = 0.0063); the frequency of tumor-specific hypermethylation was 96% (44/46) in tumors with Gleason score ≥ 7, whereas that in tumors with Gleason score 6 was 25% (1/4). Immunohistochemical analyses using these 50 cases indicated that only 8% (4/50) of cancerous tissues expressed PYCARD, whereas 80% (40/50) of corresponding normal prostate epithelial and/or basal cells expressed PYCARD. In addition, there was no relationship between PYCARD immunostaining and the Gleason score in cancerous tissue and surrounding normal tissue. Inducible expression of PYCARD inhibited cell proliferation by induction of apoptosis. These results suggest that aberrant methylation of PYCARD is a distinctive feature of prostate cancers with Gleason score ≥ 7 and may play an important role in escaping from apoptosis in prostatic tumorigenesis.The Kessler Foundation Neglect Assessment Process (KF-NAP) is an assessment tool for unilateral spatial neglect (USN), which is the scoring method for the Catherine Bergego Scale (CBS) based on detailed instructions. This study is aimed at determining the reliability and validity of the Japanese version of the KF-NAP (KF-NAP-J), evaluating the improvement of neglect assessment with KF-NAP-J, and comparing it with the original CBS for subacute stroke patients. BTK animal study We assessed subacute stroke patients admitted to our intensive rehabilitation hospital. link2 Two KF-NAP-trained occupational therapists (OTs) assessed 22 patients. Before implementing the KF-NAP at the hospital, two other OTs assessed the other 23 patients using the CBS. We evaluated the interrater reliability of the KF-NAP and CBS using intraclass correlation coefficients (ICC) for the total scores, weighted kappa statistics for each subscale, and internal consistency using Cronbach's alpha. We assessed the validity of the KF-NAP against the Behavioral Inattention Test (BIT) and Functional Independence Measure (FIM) using Spearman's correlation coefficient. The reliability of both the KF-NAP and CBS was excellent. The weighted kappa results demonstrated that each subscale was in better agreement with the KF-NAP than with the CBS. In the KF-NAP, all eight subscales in which weighted kappa could be calculated were in significant agreement, and two were almost in perfect agreement. link3 The KF-NAP moderately correlated with the subscales of BIT and FIM representing USN and activities of daily living. The USN detection rates of KF-NAP and BIT in the KF-NAP group were 63.6% and 22.7%, respectively. These results suggest that the KF-NAP, as well as the CBS, is useful to assess USN, which strongly impacts the rehabilitation outcomes in subacute stroke patients.Limited research exists about factors that influence the sustainability of preventive school mental health interventions when research support ends. This study assessed barriers and facilitators to sustaining RAP (Relax, be Aware, do a Personal rating) Club, a trauma-informed universal mental health intervention, in urban schools following efficacy trial implementation. Between 2016-2018, 13 Baltimore City schools implemented RAP Club. We evaluated RAP Club sustainability using semi-structured interviews with administrators (n=10) and school staff trained to deliver the intervention (n=11), as well as review of intervention fidelity logs (n=137) and notes from supervision calls (n=10) with school staff and research team members who implemented the program. Although most school staff described RAP Club as acceptable and beneficial, none of the 13 schools sustained the intervention. Barriers to sustainability included low self-efficacy among school staff trained to deliver the intervention, school staff turnover, logistical challenges with space and time in the regular school calendar to deliver the program, insufficient funding to sustain the program outside of the research context, and limited planning and ongoing communication between school personnel and researchers about sustainability. Recommendations for increasing post-trial program sustainability include developing sustainability plans with schools during the pre-implementation phase, enhancing ongoing support for school staff during the implementation phase, and using academic-community partnerships to facilitate sustainability and intervention scale-up during the post-implementation phase. link= BTK animal study Increasing sustainability of beneficial school-based mental health programs has the potential to reduce mental health disparities and promote health equity.
Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs).
A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies.
Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs (
= 0.39), RF and ACPAs, (
= 0.3) and RF and anti-CarP, (
= 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF.
Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.
Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.
Peginterferon beta-1a administered every 2 weeks
subcutaneous (SC) injection is approved to treat adult patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing forms of multiple sclerosis (RMS). However, associated injection site reactions (ISRs) can lead to treatment discontinuation. link2 Prior studies with interferon beta-1a reported a lower frequency of ISRs with intramuscular (IM) administration than with SC administration. IM administration of peginterferon beta-1a may therefore represent a useful alternative treatment option.
A phase I, open-label, two-period crossover study randomized healthy volunteers to receive a single dose of peginterferon beta-1a 125 mcg administered IM followed by a single 125 mcg dose administered SC after a 28-day washout or vice versa. Blood samples were collected up to 504 h post dose to determine pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The primary endpoint was assessment of bioequivalence based on maximum serum concentration (C
) and areesults demonstrate bioequivalence between peginterferon beta-1a IM and SC and support the consideration of IM injection of peginterferon beta-1a as a viable treatment option in patients with RRMS and RMS.This paper presents a low-cost, efficient, and portable in vivo method for identifying axes of rotation of the proximal interphalangeal and distal interphalangeal joints in an index finger. The approach is associated with the screw displacement representation of rigid body motion. Using the matrix exponential method, a detailed derivation of general spatial displacement of a rigid body in the form of screw displacement including the Rodrigues' formulae for rotation is presented. Then, based on a gyroscope sensor, a test framework for determining axes of rotation of finger joints is established, and experiments on finding the directions of joint axes of the PIP and DIP joints are conducted. BTK animal study The results obtained highly agree with those presented in literature through traditional but complex methods.Surface electromyography- (sEMG-) based hand grasp force estimation plays an important role with a promising accuracy in a laboratory environment, yet hardly clinically applicable because of physiological changes and other factors. One of the critical factors is the muscle fatigue concomitant with daily activities which degrades the accuracy and reliability of force estimation from sEMG signals. Conventional qualitative measurements of muscle fatigue contribute to an improved force estimation model with limited progress. This paper proposes an easy-to-implement method to evaluate the muscle fatigue quantitatively and demonstrates that the proposed metrics can have a substantial impact on improving the performance of hand grasp force estimation. Specifically, the reduction in the maximal capacity to generate force is used as the metric of muscle fatigue in combination with a back-propagation neural network (BPNN) is adopted to build a sEMG-hand grasp force estimation model. link3 Experiments are conducted in the three cases (1) pooling training data from all muscle fatigue states with time-domain feature only, (2) employing frequency domain feature for expression of muscle fatigue information based on case 1, and 3) incorporating the quantitative metric of muscle fatigue value as an additional input for estimation model based on case 1. The results show that the degree of muscle fatigue and task intensity can be easily distinguished, and the additional input of muscle fatigue in BPNN greatly improves the performance of hand grasp force estimation, which is reflected by the 6.3797% increase in R2 (coefficient of determination) value.