A multicenter study confirms CD226gene association with systemic sclerosis-related pulmonary fibrosis

Introduction: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. Methods: A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. Results: Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). Conclusion: Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Investigations into telomere biology in systemic sclerosis

Systemic sclerosis (SSc) is a complex multisystem autoimmune connective tissue disease of yet unknown aetiology. It is characterised by vascular damage, autoimmunity and progressive fibrosis in the skin and internal organs, with 2 main subsets of disease: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), classified mainly according to skin involvement. Although there has been tremendous progress in the understanding and treatment of autoimmune diseases in the last 20 years, SSc remains a disease with high morbidity and mortality, with no proven treatments that improve long-term outcome. There is therefore a need to improve the understanding of such a devastating disease to facilitate the development of future treatments and improve the prognosis for patients with SSc. Telomeres are nucleo-protein complexes, comprising tandem TTAGGG repeats at the ends of eukaryotic chromosomes, which protect the chromosomes from end-to-end fusion, recombination and degradation. There are a variety of telomere binding proteins which maintain telomere stability and function in sensing, signalling and repairing DNA damage. Telomere lengths have been used as a marker of biological aging for over a decade, and the technologies for measuring telomere lengths have also advanced in recent years. Quantitative real time PCR (QPCR) has now superseded Southern Blotting (SB) for telomere length measurements. Telomere erosion has been implicated in a wide range of diseases and its impact on autoimmune diseases remains unclear. As SSc is associated with particular autoantibodies which have been linked to telomeres, this thesis sought to explore telomere biology in SSc. Initial work measuring telomere lengths in SSc patients using the SB method revealed surprising results, with a lack of age-related telomere erosion in patients with lcSSc, which was in contrast to published literature at the time. The aim of this research was to measure telomere lengths of peripheral blood mononuclear cells (PBMC) in patients with SSc and related connective tissue diseases using QPCR, with the hypothesis that telomere lengths would be shorter in disease, and to explore telomere binding protein genes, with a view to gaining insight into any mechanistic differences in telomere biology in the different subsets of disease. Measurement of telomere lengths of PBMC from healthy controls and patients using QPCR showed that telomere lengths were significantly shorter in disease compared to controls, but when adjusted for age, there was no statistically significant difference in telomere lengths of patients with lcSSc compared to controls. Taking into account the complexity of telomere biology, it is possible that mediators of the inflammatory reaction at the systemic level or autoantibodies against nucleoprotein complexes directly or indirectly interfere with the homeostasis of telomere length in blood. This could occur through disrupting the proteins of the shelterin complex or associated factors relating to DNA repair. Hence, the gene expression of telomere binding proteins and other genes associated with inflammation and DNA repair were explored in patients with SSc using Taqman Low Density Arrays. The majority of these genes were under expressed in disease compared to controls, but when samples were age-matched, only 4 genes were under-expressed in patients with dcSSc: BCL2, POT1, SIRT6 and WRN, and 4 genes were under-expressed in lcSSc: ATM, BCL2, STAU1 and WRN. There was no correlation between telomere lengths and gene expression. These observations are intriguing, and the role of BCL2 and WRN merit further investigation in patients with SSc. This work has confirmed that telomeres shorten with age and disease, in keeping with the original hypothesis and published literature. However, there was no significant difference in age-related telomere erosion in patients with lcSSc. Gene expression analysis of telomere associated genes in SSc revealed lower expression in disease compared with controls. Whether this observation is a cause or effect of disease remains to be proven, but suggests that telomeres may be implicated in the pathophysiology of SSc and there are mechanistic differences between the subsets of disease

The development and validation of the Singapore Youth Resilience Scale (SYRESS).

The International Journal of Educational and Psychological Assessment8216-3

Fatty acid composition and phytonutrients of SO, RPO and PO.

<p>The amount of fatty acid expressed as a percentage is given in parenthesis.</p><p>SO = super olein; RPO = red palm olein; PO = palm olein.</p

Time course of effect of oil supplementation on systolic blood pressure and heart rate.

<p>The graphs show the effect of super olein (SO), red palm olein (RPO) and palm olein (PO) supplemented diets on the systolic blood pressure (SBP) and heart rate (HR) in SHR and WKY rats from 4–19 weeks of age, at 0–15 weeks treatment period. SBP and HR of treated SHR and its controls (A and B, respectively). SBP and HR of treated WKY rats and its controls (C and D, respectively). Each point represents mean±SEM (n = 6). Two-way ANOVA was used for statistical comparisons between the different treated groups and their strain-matched controls on the SBP and HR changes over the whole duration of treatment. ***<i>p<0.001</i>, compared with SHR controls; ^###<i>p<0.001</i>, compared with RPO; ^@<i>p<0.05</i>, compared with PO.</p

Calorie intake and body weight of treated and untreated SHR and WKY rats.

<p>The graphs show daily calorie intake and weekly body weight gain in SHR and WKY rats fed super olein (SO), red palm olein (RPO) and palm olein (PO) supplemented diets from 4–19 weeks of age, at 0–15 weeks of treatment period. Calorie intake of treated SHR and its controls (A), and treated WKY and its controls (B). Body weight of treated SHR and its controls (C), and treated WKY and its controls (D). Each point represents mean±SEM (n = 6).</p