Zinvolle pijn? Een empirisch onderzoek naar spiritualiteit en kwaliteit van leven bij patiënten met chronische, onverklaarde pijn

In Nederland lijden 600.000 tot 800.000 mensen aan chronische, onverklaarde pijn (COP), wat gepaard gaat met aanzienlijke functioneringsproblemen in het dagelijkse leven en lijdensdruk voor de patiënt. Het gebruikelijke biopsychosociaal verklaringsmodel van pijn blijkt tot op heden onvoldoende toereikend om de kwaliteit van leven bij patiënten met COP te verbeteren. Een benadering vanuit het biopsychosociaal-spiritueel model van zorg biedt mogelijk een aanvulling op de bestaande kennis van COP, wat de begeleiding van patiënten ten goede komt. In dit onderzoek stond de vraag centraal wat de samenhang was tussen pijnintensiteit, spiritualiteit en kwaliteit van leven bij patiënten met COP. Om dit te onderzoeken werd een exploratief cross-sectioneel vragenlijstonderzoek uitgevoerd onder 164 patiënten met COP. Met de SAIL-vragenlijst werd spiritualiteit gemeten op zeven dimensies: zingeving; vertrouwen; aanvaarding; zorg om anderen; verbondenheid met de natuur; transcendente ervaringen; en spirituele activiteiten. Twee VAS-schalen bepaalden de pijnintensiteit en de SF-36 werd gebruikt om de kwaliteit van leven te meten op twee domeinen: de fysieke en de mentale kwaliteit van leven. De data werden geanalyseerd met enkelvoudige en multiple lineaire regressieanalyses. De resultaten van dit verkennende onderzoek toonden onder meer dat er sprake was van samenhang tussen pijn en spiritualiteit, en dat er sprake was van samenhang tussen kwaliteit van leven en spiritualiteit. Ook bleek dat de respondenten significant hoger scoorden dan gezonde personen op de spiritualiteitsdimensies ‘zingeving’, ‘vertrouwen’, ‘zorg om anderen’ en ‘transcendente ervaringen’. Spiritualiteitsdimensies die gericht waren op verbondenheid met zichzelf bleken een bijdrage te leveren aan de mentale kwaliteit van leven. Vervolgonderzoek moet nader licht werpen op de causaliteit van de verbanden, waardoor duidelijk wordt op welke manier de spiritualiteitsdimensies een positieve dan wel negatieve rol spelen bij mensen met chronische, onverklaarde pijn

Temporal changes in sugar-sweetened soft drink intake and variation across municipalities in the Capital Region of Denmark

We aimed to examine the changes in sugar-sweetened soft drink intake across the Capital Region of Denmark from 2007 to 2013 and to examine the association between intake and neighbourhood socioeconomic status. The study included data from three health surveys in 2007 (n = 30,426), 2010 (n = 42,218) and 2013 (n = 34,330) in the Capital Region of Denmark. Frequency of soft drink intake was derived from questionnaires among residents aged 25–79 years and linked with information from central registers. Municipality social groups (MSG) 1–4 of decreasing affluence were defined as a composite measure. Logistic regression analyses were conducted for individuals with an appropriate soft drink intake (&lt; once/week) and for individuals with a frequent soft drink intake (≥ 3 times/week). The proportion of individuals reporting an appropriate soft drink intake increased by 71% during 2007–2013 (p &lt; 0.0001). A corresponding decrease was found in the proportion of individuals reporting a frequent soft drink intake. Compared to MSG 1, odds of an appropriate soft drink intake were significantly lower in MSG 3–4: OR = 0.87 (95%CI 0.83–0.91) and OR = 0.89 (95%CI 0.85–0.92), respectively. Compared to MSG 1, odds of a frequent soft drink intake were significantly higher in MSG 3–4: OR = 1.24 (95%CI 1.63–1.31) and 1.17 (95%CI 1.10–1.25), respectively. A significant interaction between MSG and educational level was found among individuals reporting a frequent soft drink intake (p = 0.02). The results show an encouraging reduction in frequency of soft drink intake among capital residents in the period of 2007–2013. A social gradient was observed in soft drink intake across MSG.</p

Exposure of fibrinogen and thrombin to nitric oxide donor ProliNONOate affects fibrin clot properties

Fibrin fibers form the structural backbone of blood clots. The structural properties of fibrin clots are highly dependent on formation kinetics. Environmental factors such as protein concentration, pH, salt, and protein modification, to name a few, can affect fiber kinetics through altered fibrinopeptide release, monomer association, and/or lateral aggregation. The objective of our study was to determine the effect of thrombin and fibrinogen exposed to nitric oxide on fibrin clot properties. ProliNONOate (5 [mu]mol/l) was added to fibrinogen and thrombin before clot initiation and immediately following the addition of thrombin to the fibrinogen solution. Resulting fibrin fibers were probed with an atomic force microscope to determine their diameter and extensibility and fibrin clots were analyzed for clot density using confocal microscopy. Fiber diameters were also determined by confocal microscopy and the rate of clot formation was recorded using UV-vis spectrophotometry. Protein oxidation and S-nitrosation was determined by UV-vis, ELISA, and chemiluminescence. The addition of ProliNONOate to fibrinogen or thrombin resulted in a change in clot structure. ProliNONOate exposure produced clots with lower fiber density, thicker fibers, and increased time to maximum turbidity. The effect of the exposure of nitric oxide to thrombin and fibrinogen were measured independently and indicated that each plays a role in altering clot properties. We detected thrombin S-nitrosation and protein carbonyl formation after nitric oxide exposure. Our study reveals a regulation of fibrin clot properties by nitric oxide exposure and suggests a role of peroxynitrite in oxidative modifications of the proteins. These results relate nitric oxide bioavailability and oxidative stress to altered clot properties

Classmates motivate childhood cancer patients to participate in physical activity during treatment: A qualitative study

Introduction Children with cancer experience reduced physical fitness and compromised social relationships during and following intensive treatment. This may negatively impact their quality of life. As part of the RESPECT study, we explored the motivations for participation in a physical activity programme during treatment. Methods Thirteen semi‐structured interviews were conducted with seven boys and six girls, diagnosed with paediatric cancer in 2013 and treated with chemotherapy (age 8–16 years; time from diagnosis to interview 6–16 months). Interviews were conducted in the children's homes. Results The qualitative analysis showed that children's motivations for engaging in the physical activity programme during intensive medical treatment were primarily influenced by (a) opportunity for physical activity with a classmate; (b) participation in group physical activity sessions; (c) support from significant others; and (d) improvement of physical well‐being. Main barriers included (a) poor physical well‐being; (b) compliance with medical procedures and being treated in protective isolation; and (c) limited physical activity facilities. Conclusion Despite barriers, it is possible to motivate and engage children with cancer in physical activity during intensive treatment in a paediatric oncology ward. Physical exercise and activity should be recommended and promoted from diagnosis throughout the treatment period and should include psychosocial and professional support

Chemically induced hypoxia by dimethyloxalylglycine (dmog)-loaded nanoporous silica nanoparticles supports endothelial tube formation by sustained vegf release from adipose tissue-derived stem cells

Inadequate vascularization leading to insufficient oxygen and nutrient supply in deeper layers of bioartificial tissues remains a limitation in current tissue engineering approaches to which prevascularization offers a promising solution. Hypoxia triggering pre-vascularization by enhanced vascular endothelial growth factor (VEGF) expression can be induced chemically by dimethyloxalylglycine (DMOG). Nanoporous silica nanoparticles (NPSNPs, or mesoporous silica nanoparticles, MSNs) enable sustained delivery of molecules and potentially release DMOG allowing a durable capillarization of a construct. Here we evaluated the effects of soluble DMOG and DMOG-loaded NPSNPs on VEGF secretion of adipose tissue-derived stem cells (ASC) and on tube formation by human umbilical vein endothelial cells (HUVEC)-ASC co-cultures. Repeated doses of 100 mM and 500 mM soluble DMOG on ASC resulted in 3- to 7-fold increased VEGF levels on day 9 (P<0.0001). Same doses of DMOG-NPSNPs enhanced VEGF secretion 7.7-fold (P<0.0001) which could be maintained until day 12 with 500 mM DMOG-NPSNPs. In fibrin-based tube formation assays, 100 mM DMOG-NPSNPs had inhibitory effects whereas 50 mM significantly increased tube length, area and number of junctions transiently for 4 days. Thus, DMOG-NPSNPs supported endothelial tube formation by upregulated VEGF secretion from ASC and thus display a promising tool for prevascularization of tissue-engineered constructs. Further studies will evaluate their effect in hydrogels under perfusion

Prophylactic anticoagulation with low molecular weight heparin in COVID-19: cohort studies in Denmark and Sweden

OBJECTIVES: To evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. METHODS: Using healthcare records from the capital region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. RESULTS: We included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N=432) and the pooled risk ratio was 0.89 (CI 0.61-1.29) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (CI 0.85-1.48), while we observed no increased risk of bleeding (RR 0.60, 0.14-2.59). The relative risk of venous thromboembolism was 0.68 (CI: 0.33-1.38) in Sweden. Less than 5 VTE events were observed among individuals receiving LMWH in Denmark, preventing a meaningful analysis. CONCLUSION: We found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH

A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci

A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8×10−11, GWA scan; P = 1.8×10−30, replication; P = 1.8×10−39, combined; U.K. PSA: P = 6.9×10−11). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13×10−26 in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4×10−4; U.K. PSA: P = 8.0×10−4; IL12B:rs6887695, U.S. PS, P = 5×10−5 and U.K. PSA, P = 1.3×10−3) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P = 2×10−6 for rs7993214; OR = 0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined P = 6.2×10−5 for rs6701216; OR 1.45) and a region of LD at 15q21 (combined P = 2.9×10−5 for rs3803369; OR = 1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid Arthritis)