Combined effects of CXCL8 and CXCR2 gene polymorphisms on susceptibility to systemic sclerosis

AbstractA previous study suggested that the CXCR2 (+1208) TT genotype was associated with increased risk of systemic sclerosis (SSc). In the present study, we investigated the influence of variation in the CXCL8 and CXCR2 genes on susceptibility to SSc and combined the variant alleles of these genes to analyze their effects on SSc.MethodsOne fifty one patients with SSc and 147 healthy bone marrow donors were enrolled in a case-control study. Blood was collected for DNA extraction; typing of CXCL8 (−251) T/A and CXCR2 (+1208) T/C genes was made by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by agarose gel electrophoresis.ResultsThe CXCR2-TC genotype was significantly less frequent in patients (23.8% versus 55.1% in controls; P<0.001, OR=0.26, 95%CI=0.15–0.43), whereas the CXCR2-CC genotype was significantly more frequent (44.4% versus 22.4% in controls; P<0.001, OR=2.76, 95%CI, 1.62–4.72). When CXCR2 and CXCL8 combinations were analyzed, the presence of CXCR2 T in the absence of CXCL8 A (CXCR2 T+/CXCL8 A−) was more frequent in patients than in controls (34.5% versus 3.5%; P<0.001, OR=14.50, 95%CI=5.04–41.40). However, CXCR2 TT and CXCL8 A were significantly more common in controls (100%) than in patients (58.3%) (P<0.001). Likewise, the presence of CXCR2 TC and CXCL8 A was more frequent in controls (95.1%) than in patients (75%) (P=0.004). Furthermore, the CXCR2-CC genotype in CXCL8 A was more frequent in patients (59.7% versus 0% in controls; P<0.001, adjusted OR=98.67, 95%CI=6.04–1610.8). In patients, a high frequency was observed in combination with the CXCL8 TA and AA genotypes (P<0.001; OR=28.92), whereas in controls, there was a high frequency of combination with CXCL8 T (P<0.001; OR=0.03) and TT (P<0.001; OR=0.01). Conclusions: These findings suggest a protective role of CXCL8 (−251) A in the CXCR2 (+1208) TT and TC genotypes and an increased risk of CXCL8 (−251) A in association with the CXCR2 (+1208) CC genotype in SSc patients

Combined effects of CXCL8 and CXCR2 gene polymorphisms on susceptibility to systemic sclerosis

A previous study suggested that the CXCR2 (+1208) TT genotype was associated with increased risk of systemic sclerosis (SSc). In the present study, we investigated the influence of variation in the CXCL8 and CXCR2 genes on susceptibility to SSc and combined the variant alleles of these genes to analyze their effects on SSc. Methods: One fifty one patients with SSc and 147 healthy bone marrow donors were enrolled in a casecontrol study. Blood was collected for DNA extraction; typing of CXCL8 (251) T/A and CXCR2 (+1208) T/ C genes was made by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by agarose gel electrophoresis. Results: The CXCR2-TC genotype was significantly less frequent in patients (23.8% versus 55.1% in controls; P < 0.001, OR = 0.26, 95%CI = 0.15–0.43), whereas the CXCR2-CC genotype was significantly more frequent (44.4% versus 22.4% in controls; P < 0.001, OR = 2.76, 95%CI, 1.62–4.72). When CXCR2 and CXCL8 combinations were analyzed, the presence of CXCR2 T in the absence of CXCL8 A (CXCR2 T+/CXCL8 A) was more frequent in patients than in controls (34.5% versus 3.5%; P < 0.001, OR = 14.50, 95%CI = 5.04– 41.40). However, CXCR2 TT and CXCL8 A were significantly more common in controls (100%) than in patients (58.3%) (P < 0.001). Likewise, the presence of CXCR2 TC and CXCL8 A was more frequent in controls (95.1%) than in patients (75%) (P = 0.004). Furthermore, the CXCR2-CC genotype in CXCL8 A was more frequent in patients (59.7% versus 0% in controls; P < 0.001, adjusted OR = 98.67, 95%CI = 6.04– 1610.8). In patients, a high frequency was observed in combination with the CXCL8 TA and AA genotypes (P < 0.001; OR = 28.92), whereas in controls, there was a high frequency of combination with CXCL8 T (P < 0.001; OR = 0.03) and TT (P < 0.001; OR = 0.01). ). Conclusions: These findings suggest a protective role of CXCL8 (251) A in the CXCR2 (+1208) TT and TC genotypes and an increased risk of CXCL8 (251) A in association with the CXCR2 (+1208) CC genotype in SSc patient

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis

The major pathological hallmark of the systemic sclerosis (SSc) is skin and internal organ fibrosis, which results from normal tissue architecture alterations and extracellular matrix (ECM) protein deposition. ECM components are degraded by matrix metalloproteinases (MMP). Promoter region polymorphisms in MMP genes may influence gene expression, resulting in an imbalance between ECM protein production and degradation. Here, we analyzed MMP1 -1607 1G/2G (rs1799750), MMP3 -1171 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms in relation to susceptibility to SSc and its clinical features. The patient group included 98 individuals with longstanding or recently diagnosed disease, meeting the American College of Rheumatology or LeRoy and Medsger criteria for SSc; the control group included 100 healthy blood donors. All participants were of European descent. Genotyping was performed by polymerase chain reaction followed by restriction digestion. Genotype and allele frequencies of MMP polymorphisms were similar between the two groups. In secondary analyses, significantly higher frequency of 1G/2G genotype from MMP1 polymorphism was observed for patients testing positive for antinuclear autoantibodies (P = 0.007), while 1G/1G genotype was associated with interstitial lung disease development (P = 0.018). The 6A/6A genotype from MMP3 polymorphism was absent in patients with calcinosis (P = 0.011), while the MMP3 5A/5A genotype correlated with the presence of anti-topoisomerase I antibodies (P = 0.009) and reduced diffusing capacity for carbon monoxide (P = 0.024). These results suggest that MMP polymorphisms are not associated with SSc susceptibility, although MMP1 and MMP3 variants are associated with specific SSc clinical and laboratory features

A Simple Double-Spin Closed Method for Preparing Platelet-Rich Plasma

Objective: To describe and analyze a new protocol for the extraction of platelet-rich plasma (PRP) for use in clinical practice and compare this technique with methods that have been previously described in the medical literature. Methods: Sixteen blood samples from healthy volunteers were collected. PRP was prepared using our new double-spin technique, consisting of successive centrifugation of blood samples with two different spins, without opening the container. Descriptive analysis of cell counts in baseline and PRP samples was undertaken. Comparison between cell and platelet count in baseline and PRP samples, as well as the statistical analysis, were done. Results: The mean platelet concentration ratio was 3.47 (SD: 0.85; 95% CI: 3.01-3.92; range: 2.48-5.71). The baseline whole blood platelet count correlated positively to the PRP platelet count (rP = 0.56; 95% CI: 0.09- 0.88; P = 0.023). The PRP was enriched for lymphocytes and monocytes but presented significantly lower counts of neutrophils and eosinophils in comparison to baseline. Conclusion: Results show a safe and easily reproducible method to obtain PRP for use in clinical daily practice.info:eu-repo/semantics/publishedVersio

Practical screening tools for sarcopenia in patients with systemic sclerosis

Introduction In view of the method of diagnosing sarcopenia being complex and considered to be difficult to introduce into routine practice, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends the use of the SARC-F questionnaire as a way to introduce assessment and treatment of sarcopenia into clinical practice. Only recently, some studies have turned their attention to the presence of sarcopenia in systemic sclerosis (SSc).There is no data about performance of SARC-F and other screening tests for sarcopenia in this population. Objective To compare the accuracy of SARC-F, SARC-CalF, SARC-F+EBM, and Ishii test as screening tools for sarcopenia in patients with SSc. Methods Cross-sectional study of 94 patients with SSc assessed by clinical and physical evaluation. Sarcopenia was defined according to the revised 2019 EWGSOP diagnostic criteria (EWGSOP2) with assessments of dual-energy X-ray absorptiometry, handgrip strength, and short physical performance battery (SPPB). As case finding tools, SARC-F, SARC-CalF, SARC-F+EBM and Ishii test were applied, including data on calf circumference, body mass index, limitations in strength, walking ability, rising from a chair, stair climbing, and self reported number of falls in the last year. The screening tests were evaluated through receiver operating characteristic (ROC) curves. Standard measures of diagnostic accuracy were computed using the EWGSOP2 criteria as the gold standard for diagnosis of sarcopenia. Results Sarcopenia was identified in 15 (15.9%) patients with SSc by the EWGSOP2 criteria. Area under the ROC curve of SARC-F screening for sarcopenia was 0.588 (95% confidence interval (CI) 0.420–0.756, p = 0.283). The results of sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic Odds Ratio (DOR) with the EWGSOP2 criteria as the gold standard were 40.0% (95% CI, 19.8–64.2), 81.0% (95% CI, 71.0–88.1), 2.11 (95% CI, 0.98–4.55), 0.74 (95% CI, 0.48–1.13) and 2.84 (95% CI, 0.88–9.22), respectively. SARC-CalF and SARC-F+EBM showed better sensitivity (53.3%, 95% CI 30.1–75.2 and 60.0%, 95% CI 35.7–80.2, respectively) and specificity (84.8%, 95% CI 75.3–91.1 and 86.1%, 95% CI 76.8–92.0, respectively) compared with SARC-F. The best sensitivity was obtained with the Ishii test (86.7%, 95% CI 62.1–96.3), at the expense of a small loss of specificity (73.4%, 95% CI 62.7–81.9). Comparing the ROC curves, SARC-F performed worse than SARC-CalF, SARC-F+EBM and Ishii test as a sarcopenia screening tool in this population (AUCs 0.588 vs. 0.718, 0.832, and 0.862, respectively). Direct comparisons between tests revealed differences only between SARC-F and Ishii test for sensitivity (p = 0.013) and AUC (p = 0.031). Conclusion SARC-CalF, SARC-F+EBM, and Ishii test performed better than SARC-F alone as screening tools for sarcopenia in patients with SSc. Considering diagnostic accuracy and feasibility aspects, SARC-F+EBM seems to be the most suitable screening tool to be adopted in routine care of patients with SSc

Teaching fractions through the multiple intelligences

Fractions are frequently used in daily life. However, many students have difficulty learning fraction concepts. In addition, some students begin the study of fractions with negative impressions. The writer of this article uses Howard Gardner\u27s theory of multiple intelligences to address the difficulties students face in learning fraction concepts. Dr. Howard Gardner, the creator of the Theory of Multiple Intelligences (Ml Theory), believes that it is unfair to teach all students in the same way. Students need opportunities to solve relevant problems that are meaningful to their everyday lives. Rather than concentrating on singular viewpoints and exclusive answers when studying concepts, allowing for a variety of perspectives and numerous solutions tends to engage more children in active thinking and learning. It needs to be accepted that authentic education cannot be carried out in a homogeneous setting when, in fact, all people learn differently. The activities developed in the created unit incorporate Ml approaches, allowing students to make choices about the way they learn fractions and to explore and discover connections between concepts and real life applications