Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 ...years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10
), arthritis (GDF5 p = 4 × 10
), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
Aim and Background: Adolescence is the period of transition from childhood to adulthood in which adolescents experience many changes, and their reactions to these changes are different. One of the ...maladaptive behaviors in this regard is aggression, which has long been the focus of many interventions. The present study aimed to investigate the effect of supportive psychotherapy on reducing physical aggression in male adolescents Methods and Materials: In this study, a single case method with an A-B design was used. The statistical population included male adolescents aged 12-18 who were referred to the social emergency center with symptoms of chronic aggression during the first six months of 2020, of whom three were selected by purposive sampling. After three baseline sessions, the intervention sessions began, and a supportive psychotherapy package was administered for eight sessions of 45 minutes per week. Two follow-up sessions were held two weeks and one month after the intervention, and the results were evaluated. The data were collected by the Physical Aggression subscale of the Aggression Questionnaire (1). Findings: A stable change index and recovery percentage were used to test the research hypothesis. Based on the overall recovery percentage of the three samples after treatment (42.77) and follow-up (48.02), it was concluded that supportive psychotherapy was effective in reducing physical aggression in adolescents. Conclusions: Supportive psychotherapy was effective in reducing aggression in male adolescents. This treatment controls aggressive behaviors by increasing self-confidence and awareness of the strengths and weaknesses.
Aim. Orofacial chronic neuropathic pain commonly occurs following trigeminal nerve injuries. We investigated whether swimming exercise can reduce trigeminal neuropathic pain through improving ...antioxidant capacity. Materials and Methods. Twenty-eight Wistar rats of either sex and 180–220 grams were divided into 4 groups as sham, neuropathy, neuropathy + single bout exercise, and neuropathy + 2 weeks of exercise. Trigeminal neuropathy was carried out through chronic constriction injury (CCI) of infraorbital nerve. Protocols of exercise were included a single bout session (45 minutes) and a 2-week (45 minutes/day/6 days a week) swimming exercise. Mechanical allodynia was detected using Von Frey filaments. The activity of the serum antioxidant enzymes glutathione peroxidase and superoxides dismutase was assayed using ELISA kits. Results. We found that CCI significantly reduced facial pain threshold in both sexes (P<0.05). Both swimming exercise protocols significantly reduced mechanical allodynia in female rats compared to the sham group; however, only 2 weeks of exercise were significantly effective in male rats. The activity of antioxidant enzyme glutathione peroxidase significantly (P<0.05) decreased following CCI in female rats against that in the sham group and 2-week exercise significantly (P<0.05) increased it toward the control level. The levels of glutathione peroxidase in male rats and superoxidase dismutase in both sexes were not significantly different compared to their sham groups. Conclusion. Swimming exercise alleviates trigeminal neuropathic pain in both sexes. Oxidative stress as a possible mechanism was involved in the effect of exercise on female rat trigeminal neuropathy.
Background. The present study aimed at determining the effect of emotional schema therapy on the irrational beliefs and body image of women with body deformity disorders. Methods. This was ...semi-experimental research with a pre-test-post-test design with a control group. The statistical population of this research included all women with body deformity disorders who were referred to the psychiatric centers of the 5th district of Tehran in 2021. Using the available sampling method, 30 people were selected from those who were referred to the mentioned centers. The research tools included the Ahvaz Irrational Belief and the Self-Body Multidimensional Questionnaires. Data were analyzed using multivariate analysis of covariance in SPSS-24. Results. Emotional schema therapy was effective on the irrational beliefs (the total score) and body image of women with body deformity disorders. In addition, emotional schema therapy could affect irrational beliefs in the components of expecting approval from others, avoiding problems, and showing emotional irresponsibility, but it had no significant effect on the component of being helpless against change. Conclusion. According to the findings, emotional schema therapy can be an effective method for correcting the irrational beliefs and body image of women with body deformity disorders. Practical Implications. Based on the results, therapists can use emotional schema therapy as one of the most efficient methods for treating negative beliefs and stereotypes.
Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend ...the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
A decreased estimated glomerular filtration rate (eGFR) leading to chronic kidney disease is a significant public health problem. Kidney function is a heritable trait, and recent application of ...genome-wide association studies (GWAS) successfully identified multiple eGFR-associated genetic loci. To increase statistical power for detecting independent associations in GWAS loci, we improved our recently developed quasi-adaptive method estimating SNP-specific alpha levels for the conditional analysis, and applied it to the GWAS meta-analysis results of eGFR among 783,978 European-ancestry individuals. Among known eGFR loci, we revealed 19 new independent association signals that were subsequently replicated in the United Kingdom Biobank (n = 408,608). These associations have remained undetected by conditional analysis using the established conservative genome-wide significance level of 5 × 10
. Functional characterization of known index SNPs and novel independent signals using colocalization of conditional eGFR association results and gene expression in
across 51 human tissues identified two potentially causal genes across kidney tissues:
and
, and three candidate genes across other tissues:
, and
. These colocalizations were not identified in the original GWAS. By applying our improved quasi-adaptive method, we successfully identified additional genetic variants associated with eGFR. Considering these signals in colocalization analyses can increase the precision of revealing potentially functional genes of GWAS loci.
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood ...captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
Molecular imprinting technology (MIT) was employed to fabricate polysulfone (PSf) membranes with specific nano-cavities for selective separation and enrichment of paclitaxel from a neat solution and ...also from yew tree extract. Polymer/template ratio, feed concentration, and the template extractor solvent were optimized. In accordance with the paclitaxel molecular dimension, the specific nano-cavities size was predicted to be 2.18 × 1.16 nm. The membranes were characterized in terms of pure water flux, molecular weight cut-off (MWCO), adsorption and diffusion, porosity, contact angle, and fouling. The results revealed that water flux through the molecularly imprinted membrane (MiM) is slightly less than that for the non-imprinted membrane (NiM), although the other properties relatively enhanced. For an in-depth understanding of the separation performance, the optimized membrane was analyzed by Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and diffuse reflectance spectroscopy (DRS). ATR-FTIR spectra and SEM images showed no significant difference between the imprinted and non-imprinted membranes, while DRS spectra revealed a spatial orientation in the polymer chain. At the optimum condition (paclitaxel concentration in the dope solution =0.5 wt%, feed initial concentration = 20 ppm, and ethanol/water ratio = 50:50 v/v) the MiM exhibited relatively high ability to recognize and separate paclitaxel with imprinting factor of 2.28. The reuse of the MiM up to 3 repeated cycles showed no obvious deterioration in the performance. Furthermore, in a single pass MiM could enrich paclitaxel from a crude yew tree extract, a real or complex solution, up to 48%, which could be quite encouraging from industrial and pharmaceutical points of view.
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Benzylation of DBU followed by anion exchange of the resulting salt with trifluoroacetate gave nearly quantitatively the ionic liquid Bn-DBUTFA. It is shown here to be an efficient catalyst for the ...synthesis of 1H-pyrazolo1,2-bphthalazine-5,10-diones via the three-component reaction of phthalhydrazide, aromatic aldehydes, and active α-methylene nitriles. DFT calculations at the B3LYP/SVP level and the experimental results are in agreement with a three-step mechanism for this reaction. Based on the DFT calculations, the catalytic effect largely arises from the intrinsic ionic properties of the ionic liquid rather than its action as a simple base. These calculations also predict the existence of two close-in-energy activated complexes whose rate determining roles and energies depend on their interaction with the anionic component of the ionic liquid, as Bn-DBUTFA has shown a higher catalytic activity than Bn-DBUOAc. This mechanistic approach opens up new and promising insights into the rational design of ionic liquid catalysts for the synthesis of 1H-pyrazolo1,2-bphthalazine-5,10-diones. The synthetic method presented here has several prominent advantages.
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