Factors associated with quality of life in systemic sclerosis: a cross-sectional study

© 2019, The Author(s). Introduction: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs, leading to their failure and disturbances in the morphology and function of blood vessels. The disease affects people in different ways, and identifying how the difficulties and limitations are related to quality of life may contribute to designing helpful interventions. The aim of this study was to identify factors associated with quality of life in people with SSc. Methods: This was a cross-sectional study conducted in 11 rheumatic centres in Poland. Patients diagnosed with SSc were included. Quality of life was measured using the SSc Quality of Life Questionnaire (SScQoL). The following candidate factors were entered in preliminary multivariable analysis: age, place of residence, marital status, occupational status, disease type, disease duration, pain, fatigue, intestinal problems, breathing problems, Raynaud’s symptoms, finger ulcerations, disease severity, functional disability, anxiety and depression. Factors that achieved statistical significance at the 10% level were then entered into a final multivariable model. Factors achieving statistical significance at the 5% level in the final model were considered to be associated with quality of life in SSc. Results: In total, 231 participants were included. Mean age (SD) was 55.82 (12.55) years, disease duration 8.39 (8.18) years and 198 (85.7%) were women. Factors associated with quality of life in SSc were functional disability (β = 2.854, p < 0.001) and anxiety (β = 0.404, p < 0.001). This model with two factors (functional disability and anxiety) explained 56.7% of the variance in patients with diffuse SSc and 73.2% in those with localized SSc. Conclusions: Functional disability and anxiety are significantly associated with quality of life in SSc. Interventions aimed at improving either of these factors may contribute towards improving the quality of life of people with SSc

Targeted correction of a thalassemia-associated β-globin mutation induced by pseudo-complementary peptide nucleic acids

β-Thalassemia is a genetic disorder caused by mutations in the β-globin gene. Triplex-forming oligonucleotides and triplex-forming peptide nucleic acids (PNAs) have been shown to stimulate recombination in mammalian cells via site-specific binding and creation of altered helical structures that provoke DNA repair. However, the use of these molecules for gene targeting requires homopurine tracts to facilitate triple helix formation. Alternatively, to achieve binding to mixed-sequence target sites for the induced gene correction, we have used pseudo-complementary PNAs (pcPNAs). Due to steric hindrance, pcPNAs are unable to form pcPNA–pcPNA duplexes but can bind to complementary DNA sequences via double duplex-invasion complexes. We demonstrate here that pcPNAs, when co-transfected with donor DNA fragments, can promote single base pair modification at the start of the second intron of the beta-globin gene. This was detected by the restoration of proper splicing of transcripts produced from a green fluorescent protein-beta globin fusion gene. We also demonstrate that pcPNAs are effective in stimulating recombination in human fibroblast cells in a manner dependent on the nucleotide excision repair factor, XPA. These results suggest that pcPNAs can be effective tools to induce heritable, site-specific modification of disease-related genes in human cells without purine sequence restriction

Hairpin ribozyme-antisense RNA constructs can act as molecular lassos

We have developed a novel class of antisense agents, RNA Lassos, which are capable of binding to and circularizing around complementary target RNAs. The RNA Lasso consists of a fixed sequence derived from the hairpin ribozyme and an antisense segment whose size and sequence can be varied to base pair with accessible sites in the target RNA. The ribozyme catalyzes self-processing of the 5′- and 3′-ends of a transcribed Lasso precursor and ligates the processed ends to produce a circular RNA. The circular and linear forms of the self-processed Lasso coexist in an equilibrium that is dependent on both the Lasso sequence and the solution conditions. Lassos form strong, noncovalent complexes with linear target RNAs and form true topological linkages with circular targets. Lasso complexes with linear RNA targets were detected by denaturing gel electrophoresis and were found to be more stable than ordinary RNA duplexes. We show that expression of a fusion mRNA consisting of a sequence from the murine tumor necrosis factor-α (TNF-α) gene linked to luciferase reporter can be specifically and efficiently blocked by an anti-TNF Lasso. We also show in cell culture experiments that Lassos directed against Fas pre-mRNA were able to induce a change in alternative splicing patterns

Utility of the Care Dependency Scale in predicting care needs and health risks of elderly patients admitted to a geriatric unit: a cross-sectional study of 200 consecutive patients

Halina Doroszkiewicz,1 Matylda Sierakowska,2 Marta Muszalik3 1Department of Geriatrics, Medical University of Bialystok, Bialystok, Poland; 2Department of Integrated Medical Care, Medical University of Bialystok, Bialystok, Poland; 3Department and Clinic of Geriatrics, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland Objective: The aim of the study was to evaluate the usefulness of the Polish version of the Care Dependency Scale (CDS) in predicting care needs and health risks of elderly patients admitted to a geriatric unit.Methods: This was a cross-sectional study of 200 geriatric patients aged &ge;60&nbsp;years, chronologically admitted to a geriatrics unit in Poland. The study was carried out using the Polish version of the CDS questionnaire to evaluate biopsychosocial needs and the level of care dependency.Results: The mean age of the participating geriatric patients was 81.8&plusmn;6.6. The mean result of the sum of the CDS index for all the participants was 55.3&plusmn;15.1. Detailed analysis of the results of evaluation of the respondents&rsquo; functional condition showed statistically significant differences in the levels of care dependency. Evaluation of the patients&rsquo; physical performance in terms of the ability to do basic activities of daily living (ADL) and instrumental ADL (I-ADL) showed statistically significant differences between the levels of care dependency. Patients with high dependency were more often prone to pressure ulcers &ndash; 13.1&plusmn;3.3, falls (87.2%), poorer emotional state &ndash; 6.9&plusmn;3.6, mental function &ndash; 5.1&plusmn;2.8, and more often problems with locomotion, vision, and hearing. The results showed that locomotive disability, depression, advanced age, and problem with vision and hearing are connected with increasing care dependency.Conclusion: CDS evaluation of each admitted geriatric patient enables us to predict the care needs and health risks that need to be reduced and the disease states to be improved. CDS evaluation should be accompanied by the use of other instruments and assessments to evaluate pressure ulcer risk, fall risk, and actions toward the improvement of subjective well-being, as well as correction of vision and hearing problems where possible and assistive devices for locomotion. Keywords: Care Dependency Scale, care needs, health risks, elderl

Sensitivity of splice sites to antisense oligonucleotides in vivo.

A series of HeLa cell lines which stably express beta-globin pre-mRNAs carrying point mutations at nt 654, 705, or 745 of intron 2 has been developed. The mutations generate aberrant 5' splice sites and activate a common 3' cryptic splice site upstream leading to aberrantly spliced beta-globin mRNA. Antisense oligonucleotides, which in vivo blocked aberrant splice sites and restored correct splicing of the pre-mRNA, revealed major differences in the sensitivity of these sites to antisense probes. Although the targeted pre-mRNAs differed only by single point mutations, the effective concentrations of the oligonucleotides required for correction of splicing varied up to 750-fold. The differences among the aberrant 5' splice sites affected sensitivity of both the 5' and 3' splice sites; in particular, sensitivity of both splice sites was severely reduced by modification of the aberrant 5' splice sites to the consensus sequence. These results suggest large differences in splicing of very similar pre-mRNAs in vivo. They also indicate that antisense oligonucleotides may provide useful tools for studying the interactions of splicing machinery with pre-mRNA