The effect of disgust-related side-effects on symptoms of depression and anxiety in people treated for cancer: a moderated mediation model

As maladaptive disgust responses are linked to mental health problems, and cancer patients may experience heightened disgust as a result of treatments they receive, we explored the associations between disgust-related side-effects and symptoms of depression and anxiety in people treated for cancer. One hundred and thirty two (83 women, Mage = 57.48 years) participants answered questions about their treatments, side-effects, disgust responding, and mental health. Experiencing bowel and/or bladder problems, sickness and/or nausea (referred to here as “core” disgust-related side-effects) was significantly related to greater symptoms of depression and borderline increased anxiety. Further, these links were explained by a moderated mediation model, whereby the effects of core disgust side-effects on depression and anxiety were mediated by (physical and behavioural) self-directed disgust, and disgust propensity moderated the effect of core disgust side-effects on self-disgust. These findings stress the importance of emotional responses, like disgust, in psychological adaptation to the side-effects of cancer treatments

A summer heat wave decreases the immunocompetence of the mesograzer, Idotea baltica

Extreme events associated with global change will impose increasing stress on coastal organisms. How strong biological interactions such as the host–parasite arms-race are modulated by environmental change is largely unknown. The immune system of invertebrates, in particular phagocytosis and phenoloxidase activity response are key defence mechanisms against parasites, yet they may be sensitive to environmental perturbations. We here simulated an extreme event that mimicked the European heat wave in 2003 to investigate the effect of environmental change on the immunocompetence of the mesograzer Idotea baltica. Unlike earlier studies, our experiment aimed at simulation of the natural situation as closely as possible by using long acclimation, a slow increase in temperature and a natural community setting including the animals’ providence with natural food sources (Zostera marina and Fucus vesiculosus). Our results demonstrate that a simulated heat wave results in decreased immunocompetence of the mesograzer Idotea baltica, in particular a drop of phagocytosis by 50%. This suggests that global change has the potential to significantly affect host–parasite interactions

Are white matter hyperintensities associated with neuroborreliosis? The answer is twofold

Purpose Many consider white matter hyperintensities (WMHs) to be important imaging findings in neuroborreliosis. However, evidence regarding association with WMHs is of low quality. The objective was to investigate WMHs in neuroborreliosis visually and quantitatively. Materials and methods Patients underwent brain MRI within one month of diagnosis and six months after treatment. Healthy controls were recruited. WMHs were counted by visual rating and the volume was calculated from automatic segmentation. Biochemical markers and scores for clinical symptoms and findings were used to explore association with longitudinal volume change of WMHs. Results The study included 74 patients (37 males) with early neuroborreliosis and 65 controls (30 males). Mean age (standard deviation) was 57.4 (13.5) and 57.7 (12.9) years, respectively. Baseline WMH lesion count was zero in 14 patients/16 controls, 20 in 13/11, with no difference between groups (p = 0.90). However, from baseline to follow-up the patients had a small reduction in WMH volume and the controls a small increase, median difference 0.136 (95% confidence interval 0.051–0.251) ml. In patients, volume change was not associated with biochemical or clinical markers, but with degree of WMHs (p values 0.002–0.01). Conclusion WMH lesions were not more numerous in patients with neuroborreliosis compared to healthy controls. However, there was a small reduction of WMH volume from baseline to follow-up among patients, which was associated with higher baseline WMH severity, but not with disease burden or outcome. Overall, non-specific WMHs should not be considered suggestive of neuroborreliosis.publishedVersio

Identification and characterisation of novel SNP markers in Atlantic cod: Evidence for directional selection

<p>Abstract</p> <p>Background</p> <p>The Atlantic cod (<it>Gadus morhua</it>) is a groundfish of great economic value in fisheries and an emerging species in aquaculture. Genetic markers are needed to identify wild stocks in order to ensure sustainable management, and for marker-assisted selection and pedigree determination in aquaculture. Here, we report on the development and evaluation of a large number of Single Nucleotide Polymorphism (SNP) markers from the alignment of Expressed Sequence Tag (EST) sequences in Atlantic cod. We also present basic population parameters of the SNPs in samples of North-East Arctic cod and Norwegian coastal cod obtained from three different localities, and test for SNPs that may have been targeted by natural selection.</p> <p>Results</p> <p>A total of 17,056 EST sequences were used to find 724 putative SNPs, from which 318 segregating SNPs were isolated. The SNPs were tested on Atlantic cod from four different sites, comprising both North-East Arctic cod (NEAC) and Norwegian coastal cod (NCC). The average heterozygosity of the SNPs was 0.25 and the average minor allele frequency was 0.18. <it>F</it>_{<it>ST </it>}values were highly variable, with the majority of SNPs displaying very little differentiation while others had <it>F</it>_{<it>ST </it>}values as high as 0.83. The <it>F</it>_{<it>ST </it>}values of 29 SNPs were found to be larger than expected under a strictly neutral model, suggesting that these loci are, or have been, influenced by natural selection. For the majority of these outlier SNPs, allele frequencies in a northern sample of NCC were intermediate between allele frequencies in a southern sample of NCC and a sample of NEAC, indicating a cline in allele frequencies similar to that found at the Pantophysin I locus.</p> <p>Conclusion</p> <p>The SNP markers presented here are powerful tools for future genetics work related to management and aquaculture. In particular, some SNPs exhibiting high levels of population divergence have potential to significantly enhance studies on the population structure of Atlantic cod.</p

Serological diagnostics of Lyme borreliosis:comparison of assays in twelve clinical laboratories in Northern Europe

Lyme borreliosis (LB), caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, is the most common tick-borne infection in Europe. Laboratory diagnosis of LB is mainly based on the patients' medical history, clinical signs and symptoms in combination with detection of Borrelia-specific antibodies where indirect enzyme-linked-immunosorbent assay (ELISA) is the most widely used technique. The objective of the study was to evaluate and compare the diagnostic accuracy (sensitivities and specificities) of serological tests that are currently in use for diagnosis of LB in clinical laboratories in Northern Europe, by use of a large serum panel. The panel consisted of 195 serum samples from well-characterized and classified patients under investigation for clinically suspected LB (n = 59) including patients with Lyme neuroborreliosis, Lyme arthritis, acrodermatitis chronica atrophicans, erythema migrans or other diseases (n = 112). A total of 201 serum samples from healthy blood donors were also included. The panel (396 serum samples altogether) was sent to 12 clinical laboratories (using five different ELISA methods) as blinded for group affiliation and the laboratories were asked to perform serological analysis according to their routine procedure. The results from the study demonstrated high diagnostic concordance between the laboratories using the same diagnostic assay and lower diagnostic concordance between laboratories using different diagnostic assays. For IgG, the results were in general rather homogenous and showed an average sensitivity of 88% (range 85-91%) compared to IgM which showed lower average sensitivity of 59% (range 50-67%) and more heterogeneous results between assays and laboratories.</p

Are health care professionals able to judge cancer patients' health care preferences correctly? A cross-sectional study

Background: Health care for cancer patients is primarily shaped by health care professionals. This raises the question to what extent health care professionals are aware of patients' preferences, needs and values. The aim of this study was to explore to what extent there is concordance between patients' preferences in cancer care and patients' preferences as estimated by health care professionals. We also examined whether there were gender differences between health care professionals with regard to the degree in which they can estimate patients' preferences correctly. Methods: To obtain unbiased insight into the specific preferences of cancer patients, we developed the 'Cancer patients' health care preferences' questionnaire'. With this questionnaire we assessed a large sample of cancer patients (n = 386). Next, we asked health care professionals (medical oncologists, nurses and policymakers, n = 60) to fill out this questionnaire and to indicate preferences they thought cancer patients would have. Mean scores between groups were compared using Mann-Whitney tests. Effect sizes (ESs) were calculated for statistically significant differences. Results: We found significant differences (ESs 0.31 to 0.90) between patients and professionals for eight out of twenty-one scales and two out of eight single items. Patients valued care aspects related to expertise and attitude of health care providers and accessibility of services as more important than the professionals thought they would do. Health care professionals overestimated the value that patients set on particularly organisational and environmental aspects. We found significant gender-related differences between the professionals (ESs 0.69 to 1.39) for eight out of twenty-one scales and two out of eight single items. When there were significant differences between male and female healthcare professionals in their estimation of patients health care preferences, female health care professionals invariably had higher scores. Generally, female health care professionals did not estimate patients' preferences and needs better than their male colleagues. Conclusions: Health care professionals are reasonably well able to make a correct estimation of patients preferences, but they should be aware of their own bias and use additional resources to gain a better understanding of patients' specific preferences for each patient is different and ultimately the care needs and preferences will also be unique to the person

Variants in the <em>DDX6-CXCR5</em> autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland

\ua9 2025 The Author(s). Objectives: Sj\uf6gren\u27s disease (SjD) and systemic lupus erythematosus (SLE) share genetic risk at the DDX6-CXCR5 locus (11q23.3). Identifying and functionally characterising shared SNPs spanning this locus can provide new insights into common genetic mechanisms of autoimmunity. Methods: Transdisease meta-analyses, fine-mapping, and bioinformatic analyses prioritised shared likely functional single nucleotide polymorphisms (SNPs) for allele-specific and cell type–specific functional interrogation using electromobility shift, luciferase reporter, and quantitative chromatin conformation capture assays and clustered regularly interspaced short palindromic repeat (CRISPR) gene regulation. Results: Five shared SNPs were identified as likely functional in primary human immune cells, salivary gland and kidney tissues: rs57494551, rs4936443, rs4938572, rs7117261, and rs4938573. All 5 SNPs exhibited cell type-specific and allele-specific effects on nuclear protein binding affinity and enhancer/promoter regulatory activity in immune, salivary gland epithelial, and kidney epithelial cell models. Mapping of chromatin–chromatin interactions revealed a chromatin regulatory network that expanded beyond DDX6 and CXCR5 to include PHLDB1, lnc-PHLDB1-1, BCL9L, TRAPPC4, among others. Coalescence of functional assays and multiomic data analyses indicated that these SNPs likely modulate the activity of 3 regulatory regions: intronic rs57494551 regulatory region, intergenic SNP haplotype (rs4938572, rs4936443, and rs7117261) regulatory region, and rs4938573 regulatory region upstream of the CXCR5 promoter. Conclusions: Shared genetic susceptibly at the DDX6-CXCR5 locus in SjD and SLE likely alters common mechanisms of autoimmunity, including interferon signalling (DDX6), autophagy (TRAPPC4), and lymphocytic infiltration of disease-target tissues (CXCR5). Further, using multiomic data from patients with SjD, combined with bioinformatic and in vitro functional studies, can provide mechanistic insights into how genetic risk influences the biological pathways that drive complex autoimmunity

Distribution and determinants of patient satisfaction in oncology with a focus on health related quality of life

<p>Abstract</p> <p>Background</p> <p>Cancer patients usually undergo extensive and debilitating treatments, which make quality of life (QoL) and patient satisfaction important health care assessment measures. However, very few studies have evaluated the relationship between QoL and patient satisfaction in oncology. We investigated the clinical, demographic and QoL factors associated with patient satisfaction in a large heterogeneous sample of cancer patients.</p> <p>Methods</p> <p>A cohort of 538 cancer patients treated at Cancer Treatment Centers of America^®(CTCA) was assessed. A patient satisfaction questionnaire developed in-house by CTCA was used. It covered the following dimensions of patient satisfaction: hospital operations and services, physicians and staff, and patient endorsements for themselves and others. QoL was assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30). The clinical, demographic and QoL factors were evaluated for predictive significance using univariate and multivariate logistic regression.</p> <p>Results</p> <p>The mean age of our patient population was 54.1 years (SD = 10.5, range 17-86), with a slight preponderance of females (57.2%). Breast cancer (n = 124) and lung cancer (n = 101) were the most frequent cancer types. 481 (89.4%) patients were "very satisfied" with their overall experience. Age and several QoL function and symptom scales were predictive of overall patient satisfaction upon univariate analysis. In the multivariate modeling, only those with a score above the median on the fatigue measure (i.e. worse fatigue) had reduced odds of 0.28 of being very satisfied (p = 0.03).</p> <p>Conclusion</p> <p>Patient fatigue, as reported by the QoL fatigue scale, was an independent significant predictor of overall patient satisfaction. This finding argues for special attention and programs for cancer patients who report higher levels of fatigue given that fatigue is the most frequently reported symptom in cancer patients.</p

Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.

Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.We thank all the research and clinical staff, consortium investigators, and study participants (detailed in Supplementary Information), and funding agencies who made this study possible. The content of this publication is solely the responsibility of the authors and does not represent the official views of the funding agencies listed below. Research reported in this publication was supported by the National Institutes of Health (NIH): R01AR073855 (C.J.L.), R01AR065953 (C.J.L.), R01AR074310 (A.D.F.), P50AR060804 (K.L.S.), R01AR050782 (K.L.S), R01DE018209 (K.L.S.), R33AR076803 (I.A.), R21AR079089 (I.A.); NIDCR Sjögren’s Syndrome Clinic and Salivary Disorders Unit were supported by NIDCR Division of Intramural Research at the National Institutes of Health funds - Z01-DE000704 (B.W.); Birmingham NIHR Biomedical Research Centre (S.J.B.); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 – Projektnummer 390874280 (T.W.); Research Council of Norway (Oslo, Norway) – Grant 240421 (TR.R.), 316120 (M.W-H.); Western Norway Regional Health Authority (Helse Vest) – 911807, 912043 (R.O.); Swedish Research Council for Medicine and Health (L.R., G.N., M.W-H.); Swedish Rheumatism Association (L.R., G.N., M.W-H.); King Gustav V’s 80-year Foundation (G.N.); Swedish Society of Medicine (L.R., G.N., M.W-H.); Swedish Cancer Society (E.B.); Sjögren’s Syndrome Foundation (K.L.S.); Phileona Foundation (K.L.S.). The Stockholm County Council (M.W-H.); FOREUM Foundation for Research in Rheumatology (R.J., M.W-H). The Swedish Twin Registry is managed through the Swedish Research Council - Grant 2017-000641. The French ASSESS (Atteinte Systémique et Evolution des patients atteints de Syndrome de Sjögren primitive) was sponsored by Assistance Publique-Hôpitaux de Paris (Ministry of Health, PHRC 2006 P060228) and the French society of Rheumatology (X.M.). We want to acknowledge the following invesigators who recruited patients: Jacques-Eric Gottenberg, Valerie Devauchelle-Pensec, Jean Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Emmanuelle Dernis, Stéphanie Rist, Damien Sene, Olivier Vittecoq. We also thank Sarah Tubiana and all staff members of the Bichat Hospital Biological Resource Center (Paris) for centralizing and managing biological collection. We also thank Rezvan Kiani Dehkordi, Karolina Tandre, Käth Nilsson, Marianne Eidsheim, Kjerstin Jacobsen, Ingeborg Kvivik and Kjetil Bårdsen for collecting patient blood samples. We acknowledge the SNP&SEQ Technology Platform, Uppsala, part of National Genomics Infrastructure (NGI) Sweden, for genotyping of Scandinavian samples, and the Swedish Twin Registry for access to data. The SNP&SEQ Technology Platform was supported by Science for Life Laboratory, Uppsala University, the Knut and Alice Wallenberg Foundation and the Swedish Research Council. Last, we thank the investigators for the following dbGaP studies: Phs000428.v2.p2: This study used control data from the Health and Retirement Study in dbGaP (phs000428.v2.p2) submitted by David Weir, PhD at the University of Michigan and funded by the National Institute of Aging RC2 AG036495 and RC4 AG039029. Phs000672.v1.p1: Genotype data from the Sjögren’s International Collaborative Clinical Alliance (SICCA) Registry was obtained through dbGAP accession number phs000672.v1.p1. This study was supported by the National Institute of Dental and Craniofacial Research (NIDCR), the National Eye Institute, and the Office of Research on Women’s Health through contract number N01-DE-32636. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health (NIH) to the Johns Hopkins University (contract numbers HHSN268200782096C, HHSN268201100011I, HHSN268201200008I). Funds for genotyping were provided by the NIDCR through CIDR’s NIH contract. Assistance with data cleaning and imputation was provided by the University of Washington. We thank investigators from the following studies that provided DNA samples for genotyping: the Genetic Architecture of Smoking and Smoking Cessation, Collaborative Genetic Study of Nicotine Dependence (phs000404.v1.p1); Age-Related Eye Disease Study (AREDS) - Genetic Variation in Refractive Error Substudy (phs000429.v1.p1); and National Institute of Mental Health’s Human Genetics Initiative (phs000021.v3.p2, phs000167.v1.p1). We thank the many clinical collaborators and research participants who contributed to this research. Phs000196.v3.p1: Investigators and Parkinson Disease patients that contributed to this Genome-wide Association Study of Parkinson Disease. phs000187.v1.p1: Research support to collect data and develop an application to support the High Density SNP Association Analysis of Melanoma project was provided by 3P50CA093459, 5P50CA097007, 5R01ES011740, and 5R01CA133996