Orbitofrontal dysfunction predicts poor prognosis in chronic migraine with medication overuse

Chronic migraine patients are at risk of developing a medication overuse. Brain functional studies in these patients have demonstrated an orbitofrontal hypometabolism, persistent after overuse cessation. Orbitofrontal dysfunction is also present in addiction and thus could predispose migraineurs to medication overuse. The aim of this study was to investigate if orbitofrontal dysfunction can be demonstrated in patients with chronic migraine and medication overuse by performing a systematic neuropsychological evaluation focused on tests that assess frontal lobe function. Second, to establish whether it is related to the outcome of these patients. We prospectively studied 42 chronic migraine patients with medication overuse, 42 episodic migraineurs and 41 controls on a battery of neuropsychological tasks evaluating the orbitofrontal and dorsolateral functioning. Depression, anxiety, and personality traits were also assessed. Chronic migraineurs with medication overuse showed a significant impairment in orbitofrontal task performance and higher depression scores as compared to episodic migraineurs and controls. Dorsolateral dysfunction was present in both groups of migraneurs, who also had higher rates of anxiety as compared to controls. After 1 year of follow-up, migraine patient’s outcome was classified according to their medication overuse status. A negative outcome that included persistent or new-onset medication overuse was present in 34% of migraineurs and was associated with baseline poor orbitofrontal task performance, and with mild dorsolateral dysfunction, higher rates of depression, anxiety and neuroticism-anxiety traits. Formal education and years with migraine did not influence outcome. Orbitofrontal dysfunction is present in patients with chronic migraine and medication overuse, and associates with a poor outcome at 1 year of follow-up. Neuropsychological evaluation in migraine may help to detect patients prone to overuse so that appropriate therapeutic attitudes can be taken

Response mapping methods to estimate the EQ-5D-5L from the Western Ontario McMaster Universities Osteoarthritis in patients with hip or knee osteoarthritis

Objectives: The mapping technique can estimate generic preference-based measure scores through a specific measure that cannot be used in economic evaluations. This study compared 2 response mapping methods to estimate EQ-5D-5L scores using the Western Ontario McMaster Universities Osteoarthritis (WOMAC). Methods: The sample consisted of 758 patients with the hip or knee osteoarthritis recruited in baseline. Bayesian networks (BN) and multinomial logistic regression (ML) were used as response mapping models. Predictions were obtained using the 6-month follow-up as a validation sample. The mean absolute error, mean squared error, deviation from the root mean squared error and intraclass correlation coefficient were calculated as precision measures. Results: There was 5.5% of missing data, which was removed. The mean age was 69.6 years (standard deviation = 10.5), with 61.6% of women. The BN model presented lower mean absolute error, mean squared error, root mean squared error and higher intraclass correlation coefficient than the ML model. Only the WOMAC items pain and physical function items were related with the EQ-5D-5L dimensions. Conclusion: BN response mapping models are more robust methods, with better prediction results, than ML models. The BN model also provided a graphic representation of the dependency relationships between the EQ-5D-5L dimensions and the different WOMAC items that could be useful in the clinical investigation of patients with hip or knee osteoarthritis

A prospective study of the association of patient expectations with changes in health-related quality of life outcomes, following total joint replacement

BACKGROUND: Patient expectations regarding surgery may be related to outcomes in total joint replacement (TJR). The aim of this study was to determine the association of patient expectations with health related quality of life (HRQoL) outcomes measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form 12 (SF-12) and satisfaction with current symptoms measured on a 4-point Likert scale, one year after surgery, adjusting for Body Mass Index (BMI), age, gender, joint, education, previous intervention and baseline scores. METHODS: Consecutive patients preparing for TJR of the knee or hip due to primary osteoarthritis (OA) in 15 hospitals in Spain were recruited for the study. Patients completed questionnaires before surgery and 12 months afterwards: five questions about expectations before surgery; an item to measure satisfaction; two HRQoL instruments—WOMAC and SF-12; as well as questions about sociodemographic information. To determine the association of patient expectations at baseline, with changes in HRQoL 12 months after surgery and with satisfaction, general linear models and logistic regression analysis were performed. RESULTS: A total of 892 patients took part in the study. Patients who had higher pain relief or ability to walk expectations improved more in HRQoL at 12 months. Moreover, patients with high daily activity expectations were more satisfied. CONCLUSIONS: Patients with higher baseline expectations for TJR, improved more in HRQoL at one year and had more likelihood to be satisfied than patients with lower expectations, adjusted for BMI, age, gender, joint, education, previous intervention and HRQoL baseline scores

Gender differences in the decision-making process for undergoing total knee replacement

Acord transformatiu CRUE-CSICThis project was supported by Instituto de Salud Carlos III, Ministry of Health, Spain (grant number PI15/01264).Objective: To assess gender differences in the decision-making process for treatment of knee osteoarthritis (OA). Methods: A secondary analysis of a randomized trial was conducted (n = 193). Knowledge of OA and total knee replacement (TKR), decisional conflict, satisfaction with the decision-making process, treatment preference and TKR uptake 6 months later were compared by gender. Multivariate regression models were developed to identify gender-specific predictors. Results: Women showed less knowledge (MD = −7.68, 95% CI: −13.9, −1.46, p = 0.016), reported less satisfaction (MD = −6.95, 95% CI: −11.7, −2.23, p = 0.004) and gave more importance to avoiding surgery (U = 2.09, p = 0.019). In women, more importance attributed to the time needed to relieve symptoms significantly reduced the odds of surgery (OR = 0.76, p = 0.016). Conclusion: The provision of information and/or promotion of shared decision-making could be of lower quality in female patients, although other explanations such as differences in information needs or preference for involvement in decision-making cannot be ruled out with the current evidence. Given the study's limitations, especially regarding the sample size, further confirmation is needed. Practice implications: A systematic, shared decision-making approach in consultation is needed to avoid potential gender-based biases

Transcription Factor Binding Site Enrichment Analysis In Co-Expression Modules In Celiac Disease

The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified in the acute and chronic responses to gliadin using expression data from a previous microarray study in duodenal biopsies. Transcription factor binding site (TFBS) and Gene Ontology (GO) annotation enrichment analyses were performed in differentially co-expressed genes (DCGs) and selection of candidate regulators was performed. Expression of candidates was measured in clinical samples and the activation of the TFs was further characterized in C2BBe1 cells upon gliadin challenge. Enrichment analyses of the DCGs identified 10 TFs and five were selected for further investigation. Expression changes related to active CD were detected in four TFs, as well as in several of their in silico predicted targets. The activation of TFs was further characterized in C2BBe1 cells upon gliadin challenge, and an increase in nuclear translocation of CAMP Responsive Element Binding Protein 1 (CREB1) and IFN regulatory factor-1 (IRF1) in response to gliadin was observed. Using transcriptome-wide co-expression analyses we are able to propose novel genes involved in CD pathogenesis that respond upon gliadin stimulation, also in non-celiac models.The authors thank the technical and human support provided by SGIker of the UPV/EHU. The work was funded by ISCIII Research Project Grants PI13/01201 and PI16/00258, cofunded by the European Union ERDF/ESF "A way to make Europe" and by Basque Department of Health project 2011/111034 to JRB and Basque Department of Health project 2015/111068 to I.S., N.F.-J. was supported by an IARC Postodctoral Fellowship (FP7 Marie Curie Actions-People-COFUND) and a Postdoctoral Fellowship from the Basque Department of Education. I.R.-G. and A.J.-M. are supported by predoctoral fellowship grants from the UPV/EHU and the Basque Department of Education, respectively

MAGI2 Gene Region and Celiac Disease

Celiac disease (CD) patients present a loss of intestinal barrier function due to structural alterations in the tight junction (TJ) network, the most apical unions between epithelial cells. The association of TJ-related gene variants points to an implication of this network in disease susceptibility. This work aims to characterize the functional implication of TJ-related, disease-associated loci in CD pathogenesis. We performed an association study of 8 TJ-related gene variants in a cohort of 270 CD and 91 non-CD controls. The expression level of transcripts located in the associated SNP region was analyzed by RT-PCR in several human tissues and in duodenal biopsies of celiac patients and non-CD controls. (si)RNA-driven silencing combined with gliadin in the Caco2 intestinal cell line was used to analyze the implication of transcripts from the associated region in the regulation of TJ genes. We replicated the association of rs6962966*A variant [p = 0.0029; OR = 1.88 (95%1.24-2.87)], located in an intron of TJ-related MAGI2 coding gene and upstream of RP4-587D13.2 transcript, bioinformatically classified as a long non-coding RNA (lncRNA). The expression of both genes is correlated and constitutively downregulated in CD intestine. Silencing of lncRNA decreases the levels of MAGI2 protein. At the same time, silencing of MAGI2 affects the expression of several TJ-related genes. The associated region is functionally altered in disease, probably affecting CD-related TJ genes.This work was partially funded by the Basque Department of Education grant IT1281-19 and ISCIII Research Project PI16/00258, cofunded by the European Union ERDF, A way to make Europe to JB. AC-R is supported by an Ikerbasque Fellowship and funded by a research project grant 2017111082 from the Basque Goverment. IS was funded by a research project grant 2015111068 from the Basque Department of Health. AJ-M and AO-G are predoctoral fellows funded by FPI grants from the Basque Department of Education, Universities and Research and IR-G and MS are predoctoral fellows funded by the University of Basque Country

Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

first_page settings Open AccessArticle Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age by Diego Delgado 1, Ane Miren Bilbao 2, Maider Beitia 1, Ane Garate 1, Pello Sánchez 1, Imanol González-Burguera 3,4, Amaia Isasti 4,5, Maider López De Jesús 4,5,6, Jone Zuazo-Ibarra 7, Alejandro Montilla 7 [OrcID] , María Domercq 7 [OrcID] , Estibaliz Capetillo-Zarate 7,8, Gontzal García del Caño 3,4 [OrcID] , Joan Sallés 4,5,6, Carlos Matute 7 and Mikel Sánchez 1,2,* 1 Advanced Biological Therapy Unit, Hospital Vithas Vitoria, 01008 Vitoria-Gasteiz, Spain 2 Arthroscopic Surgery Unit, Hospital Vithas Vitoria, 01008 Vitoria-Gasteiz, Spain 3 Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01008 Vitoria-Gasteiz, Spain 4 Bioaraba, Neurofarmacología Celular y Molecular, 01008 Vitoria-Gasteiz, Spain 5 Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01008 Vitoria-Gasteiz, Spain 6 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain 7 Achucarro Basque Center for Neuroscience, CIBERNED and Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU), 48940 Leioa, Spain 8 IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain * Author to whom correspondence should be addressed. Academic Editor: Francesca Santilli Int. J. Mol. Sci. 2021, 22(4), 1725; https://doi.org/10.3390/ijms22041725 Received: 24 November 2020 / Revised: 12 January 2021 / Accepted: 3 February 2021 / Published: 9 February 2021 (This article belongs to the Section Molecular Endocrinology and Metabolism) Download PDF Browse Figures Citation Export Abstract Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.This work was funded by the Provincial Council of Alava through the AlavaInnova Program, Basque Government through the GAITEK Program, Ministry of Economy, Industry and Competitiveness (CTQ2017-85686-R), Spanish Ministry of Education and Science (PID2019-109724RB-I00), Basque Government (IT1203-19, IT1230-19, and KK-2020/00034) and Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED)

The EPICTER score: a bedside and easy tool to predict mortality at 6 months in acute heart failure

Aims: Estimating the prognosis in heart failure (HF) is important to decide when to refer to palliative care (PC). Our objective was to develop a tool to identify the probability of death within 6 months in patients admitted with acute HF. Methods and results: A total of 2848 patients admitted with HF in 74 Spanish hospitals were prospectively included and followed for 6 months. Each factor independently associated with death in the derivation cohort (60% of the sample) was assigned a prognostic weight, and a risk score was calculated. The accuracy of the score was verified in the validation cohort. The characteristics of the population were as follows: advanced age (mean 78 years), equal representation of men and women, significant comorbidity, and predominance of HF with preserved ejection fraction. During follow-up, 753 patients (26%) died. Seven independent predictors of mortality were identified: age, chronic obstructive pulmonary disease, cognitive impairment, New York Heart Association class III-IV, chronic kidney disease, estimated survival of the patient less than 6 months, and acceptance of a palliative approach by the family or the patient. The area under the ROC curve for 6 month death was 0.74 for the derivation and 0.68 for the validation cohort. The model showed good calibration (Hosmer and Lemeshow test, P value 0.11). The 6 month death rates in the score groups ranged from 6% (low risk) to 54% (very high risk). Conclusions: The EPICTER score, developed from a prospective and unselected cohort, is a bedside and easy-to-use tool that could help to identify high-risk patients requiring PC

Influence of depression on survival of colorectal cancer patients drawn from a large prospective cohort

Objective The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis. Methods This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS-D) at 5 years of follow-up. Survival was analysed using the Kaplan–Meier method and Cox regression models. Results According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21–1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51–0.76), age (>70 years: HR = 3.78; 95% CI: 1.94–7.36), need for help (yes: HR = 1.43; 95% CI: 1.17–1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16–1.82), tumour size (T3–T4: HR = 1.56; 95% CI: 1.22–1.99), nodule staging (N1–N2: HR = 2.46; 95% CI: 2.04–2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55–0.91). Conclusions There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.Funding for open Access charge: Universidad de Málaga / CBUA. This study was supported by public grant from Instituto de Salud Carlos III (PI09/90397, PS09/00314, PS09/00746, PI09/90460, PI/0990490, PI13/01692, PI13/00013, PI18/01181, Pi18/01589) and was co-funded by the European Regional Development fund

The Spanish version of the reflective functioning questionnaire: Validity data in the general population and individuals with personality disorders

INTRODUCTION: Mentalization or reflective functioning (RF) is the capacity to interpret oneself or the others in terms of internal mental states. Its failures have been linked to several mental disorders and interventions improving RF have a therapeutic effect. Mentalizing capacity of the parents influences the children's attachment. The Reflective Functioning Questionnaire (RFQ-8) is a widely used tool for the assessment of RF. No instrument is available to assess general RF in Spanish-speaking samples. The aim of this study is to develop a Spanish version of the RFQ-8 and to evaluate its reliability and validity in the general population and in individuals with personality disorders. METHODS: 602 non-clinical and 41 personality disordered participants completed a Spanish translation of the RFQ and a battery of self-reported questionnaires assessing several RF related constructs (alexithymia, perspective taking, identity diffusion and mindfulness), psychopathology (general and specific) and interpersonal problems. Temporal stability was tested in a non-clinical sub-sample of 113 participants. RESULTS: Exploratory and confirmatory factor analyses suggested a one-factor structure in the Spanish version of the RFQ-8. RFQ-8 understood as a single scale was tested, with low scorings reflecting genuine mentalizing, and high scorings uncertainty. The questionnaire showed good internal consistence in both samples and moderate temporal stability in non-clinical sample. RFQ correlated significantly with identity diffusion, alexithymia, and general psychopathology in both samples; and with mindfulness, perspective taking, and interpersonal problems in clinical sample. Mean values of the scale were significantly higher in the clinical group. DISCUSSION: This study provides evidence that the Spanish version of the RFQ-8, understood as a single scale, has an adequate reliability and validity assessing failures in reflective functioning (i.e., hypomentalization) in general population and personality disorders