Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS). METHODS: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up). RESULTS: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025). DISCUSSION: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.

Biomarcadores sanguíneos, de orina y conductas autolesivas e intentos de suicidio repetidos en los adolescentes / Blood and urine biomarkers and repeated self-injurious behaviors and suicide attempts in adolescents

Hay evidencia parcial de que los niveles elevados de la β-endorfina sanguínea se asocian a la adicción suicida en los adultos, pero apenas hay datos sobre los adolescentes. La β-endorfina sanguínea, con un importante papel en los mecanismos de gestión de las adicciones, puede inducir euforia y felicidad, recompensar y reforzar el comportamiento suicida. Para probar si los grandes repetidores de intentos de suicidio (5 o más intentos de suicidio) y de conductas autolesivas (20 o más episodios de autolesiones) tienen unos niveles de biomarcadores más elevados, se selecciona una muestra de 43 pacientes de entre 12 y 17 años que acuden al Servicio de Urgencias Psiquiátricas en el Hospital Universitario Puerta de Hierro Majadahonda. Diez presentan 5 o más intentos de suicidio, 35 presentan 20 o más episodios autolesivos y 10 presentan ambas características, y la mayoría de los adolescentes cumplían criterios de adicción para autolesiones y suicidio. Los resultados sugieren que todos los pacientes que presentaban adicción al suicidio también presentaban adicción a la autolesión. Los niveles de ACTH, cortisol y β-endorfina sanguíneos y de cortisol en orina fueron muy elevados, pero no diferenciaban a los grandes repetidores del resto de adolescentes. (AU)

There is partial evidence that elevated levels of blood β-endorphin are associated with suicidal addiction in adults, but hardly any data on adolescents. Blood β-endorphin, with an important role in addiction management mechanisms, can induce euphoria and happiness, reward and reinforce suicidal behavior. To test whether high repeaters of suicide attempts (5 or more suicide attempts) and self-injurious behaviors (20 or more episodes of self-injury) have higher biomarker levels, a sample of 43 patients aged 12-17 years attending the Psychiatric Emergency Department at the Hospital Universitario Puerta de Hierro Majadahonda is recruited. Ten present 5 or more suicide attempts, 35 present 20 or more self-injurious episodes and 10 present both characteristics, and most of the adolescents meet addiction criteria for self-injury and suicide. The results suggest that all patients with addiction to suicide also had addiction to self-injury. Blood ACTH, cortisol and β-endorphin and urine cortisol levels were very elevated, but did not differentiate heavy repeaters from the rest of the adolescents. (AU)

Response to Fingolimod in Multiple Sclerosis Patients Is Associated with a Differential Transcriptomic Regulation.

Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (five responders and five non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signaling pathways. These DEGs were predominantly immune related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). The S1P, NF-kB and TCR signaling pathways were differentially modulated in responder and non-responder patients. These transcriptomic differences offer the potential of being exploited as biomarkers of a clinical response to fingolimod.

Cancer-Related Fatigue and Circulating Biomarkers in Breast Cancer Survivors.

PURPOSE: Cancer-related fatigue (CRF) is the most common and disruptive symptom experienced by cancer survivors and because of its frequency and severity is especially worrisome in breast cancer survivors (BCS). Despite a great deal of research, the mechanisms underlying CRF have not been determined. The present study aims to describe associations between CRF in BCS and different blood biomarkers. METHODS: A descriptive and cross-sectional study was conducted. A set of biomarkers assessing inflammation were measured in BCS: C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor (TNF); HPA axis dysfunction (cortisol), autonomic dysfunction (noradrenaline); oxidative stress (8-OH deoxyguanosine); insulin resistance markers (insulin, IGF-I, IGFBP3) and sexual hormones (estrogens, progesterone, testosterone). RESULTS: NLR (p = .00) and cortisol (p = .02) were positive and negatively associated with CRF, respectively. The rest of the blood markers were not associated with CRF. CONCLUSION: Our results increase the evidence on pathophysiological mechanisms driving CRF in BCS. However, longitudinal studies are needed to explore the role of these factors as potential causal mechanisms.

Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis.

BACKGROUND: We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS). METHODS: A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods. RESULTS: Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change. CONCLUSIONS: Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.

Seroprevalence of SARS-CoV-2 in Patients with Multiple Sclerosis under Disease-Modifying Therapies: A Multi-Centre Study.

BACKGROUND: The EMCOVID project conducted a multi-centre cohort study to investigate the impact of COVID-19 on patients with Multiple Sclerosis (pwMS) receiving disease-modifying therapies (DMTs). The study aimed to evaluate the seroprevalence and persistence of SARS-CoV-2 antibodies in MS patients enrolled in the EMCOVID database. The DMTs were used to manage MS by reducing relapses, lesion accumulation, and disability progression. However, concerns arose regarding the susceptibility of pwMS to COVID-19 due to potential interactions between SARS-CoV-2 and the immune system, as well as the immunomodulatory effects of DMTs. METHODS: This prospective observational study utilized data from a Multiple Sclerosis and COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data, SARS-CoV-2 serology, and symptoms of COVID-19 were extracted for pwMS receiving any type of DMT. The relationship between demographics, MS phenotype, DMTs, and COVID-19 was evaluated. The evolution of SARS-CoV-2 antibodies over a 6-month period was also assessed. RESULTS: The study included 709 pwMS, with 376 patients providing samples at the 6-month follow-up visit. The seroprevalence of SARS-CoV-2 antibodies was higher among pwMS than the general population, with Interferon treatment being significantly associated with greater seroprevalence (16.9% vs. 8.4%; p 0.003). However, no other specific DMT showed a significant association with antibody presence. A total of 32 patients (8.5%) tested positive for IgG, IgM, or IgA antibodies against SARS-CoV-2 at baseline, but then tested negative at 6 months. Most of the pwMS in the cohort were asymptomatic for COVID-19 and, even among symptomatic cases, the prognosis was generally favourable. CONCLUSION: pwMS undergoing DMTs exhibited a higher seroprevalence of COVID-19 than the general population. Interferon treatment was associated with a higher seroprevalence, suggesting a more robust humoral response. This study provides valuable insights into the seroprevalence and persistence of SARS-CoV-2 antibodies in pwMS and contributes to our understanding of the impact of COVID-19 amongst this population.

Dimethyl fumarate-related immune and transcriptional signature is associated with clinical response in multiple sclerosis-treated patients.

Background and objective: Dimethyl fumarate (DMF) is an immunomodulatory drug approved for the therapy of multiple sclerosis (MS). The identification of response biomarkers to DMF is a necessity in the clinical practice. With this aim, we studied the immunophenotypic and transcriptomic changes produced by DMF in peripheral blood mononuclear cells (PBMCs) and its association with clinical response. Material and methods: PBMCs were obtained from 22 RRMS patients at baseline and 12 months of DMF treatment. Lymphocyte and monocyte subsets, and gene expression were assessed by flow cytometry and next-generation RNA sequencing, respectively. Clinical response was evaluated using the composite measure "no evidence of disease activity" NEDA-3 or "evidence of disease activity" EDA-3 at 2 years, classifying patients into responders (n=15) or non-responders (n=7), respectively. Results: In the whole cohort, DMF produced a decrease in effector (TEM) and central (TCM) memory T cells in both the CD4+ and CD8+ compartments, followed by an increase in CD4+ naïve T cells. Responder patients presented a greater decrease in TEM lymphocytes. In addition, responder patients showed an increase in NK cells and were resistant to the decrease in the intermediate monocytes shown by non-responders. Responder patients also presented differences in 3 subpopulations (NK bright, NK dim and CD8 TCM) at baseline and 4 subpopulations (intermediate monocytes, regulatory T cells, CD4 TCM and CD4 TEMRA) at 12 months. DMF induced a mild transcriptional effect, with only 328 differentially expressed genes (DEGs) after 12 months of treatment. The overall effect was a downregulation of pro-inflammatory genes, chemokines, and activators of the NF-kB pathway. At baseline, no DEGs were found between responders and non-responders. During DMF treatment a differential transcriptomic response was observed, with responders presenting a higher number of DEGs (902 genes) compared to non-responders (189 genes). Conclusions: Responder patients to DMF exhibit differences in monocyte and lymphocyte subpopulations and a distinguishable transcriptomic response compared to non-responders that should be further studied for the validation of biomarkers of treatment response to DMF.

Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer.

Clinical management of breast cancer (BC) metastasis remains an unmet need as it accounts for 90% of BC-associated mortality. Although the luminal subtype, which represents >70% of BC cases, is generally associated with a favorable outcome, it is susceptible to metastatic relapse as late as 15 years after treatment discontinuation. Seeking therapeutic approaches as well as screening tools to properly identify those patients with a higher risk of recurrence is therefore essential. Here, we report that the lipid-degrading enzyme fatty acid amide hydrolase (FAAH) is a predictor of long-term survival in patients with luminal BC, and that it blocks tumor progression and lung metastasis in cell and mouse models of BC. Together, our findings highlight the potential of FAAH as a biomarker with prognostic value in luminal BC and as a therapeutic target in metastatic disease.

Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.

The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline and after 12 and 24 months of DMF treatment. MS patients presented lower levels of 2-AG and PEA compared to HD. 2-AG increased at 24 months, reaching HD levels. AEA and PEA remained stable at 12 and 24 months. OEA increased at 12 months and returned to initial levels at 24 months. Patients who achieved no evidence of disease activity (NEDA3) presented the same modulation over time as EDA3 patients. PEA was modulated differentially between females and males. Our results show that the ECS is dysregulated in MS patients. The increase in 2-AG and OEA during DMF treatment suggests a possible role of DMF in ECS modulation.

Biosignature of self-injury behaviors in adolescence: Role of ß-endorphin in an acute inpatient unit.

Self-injurious behavior (SIB) (either non-suicidal self-injury, NSSI; or suicide attempts, SA) is a common reason for adolescent psychiatric emergency hospitalizations. Altered basal serum ß-endorphin (BE) levels have been reported in adults with a history of SIB, but information is lacking in adolescents. We analyzed the psychoclinical profile and serum BE level of 39 adolescents admitted to the acute unit at a hospital in Spain due to SIB. The Mean (SD) serum BE level was high (190.53 ± 74.83). Regarding time sequence, the onset age of NSSI and SA were related (p < 0.001). The older the onset age of NSSI, the shorter the transition between NSSI and the onset of SA behavior (p = 0.05), but this difference does not lead the variation of BE (p = 0.81). Patients diagnosed with depression had lower serum BE levels than adolescents with other diagnoses (p = 0.03). Although adolescents who seem to be addicted to SIB had higher levels of BE, this finding was not statistically significant. The relationship between serum BE levels and SIB in adolescents requires further investigation.

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease.

BACKGROUND: Infection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus. METHODS: 318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed. RESULTS: Four SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12-0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14-0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12-115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26-125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities. CONCLUSIONS: Different genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.

Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19.

INTRODUCTION: Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. METHODS: This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, ß2 microglobulin and albumin levels pre/post-dialysis and on 1st-2nd week. We compared levels among both techniques and control group (HD without COVID-19). RESULTS: We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and ß2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. DISCUSSION: Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. CONCLUSION: HDx appears to provide better clearance for TNFα and ß2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

Exploring the potential relationship between collagen cross-linking and impaired myocardial relaxation in Marfan syndrome: An observational study using serum biomarkers.

BACKGROUND: Increased collagen cross-linking (CCL) has been described in hypertensive cardiomyopathy by means of reduced serum ratio of serum carboxyterminal telopeptide of collagen type I (CITP) to matrix metalloproteinase-1 (MMP1). Previous studies have demonstrated the existence of primary impaired diastole in patients with Marfan syndrome (MFS), but little is known about the pathophysiology of this condition. METHODS: 60 MFS patients (without previous cardiovascular surgery or significant valvular regurgitation) and 24 healthy controls (age and sex-matched) were enrolled. All participants underwent a comprehensive transthoracic echocardiographic study, including left atrial and left ventricular speckle-tracking strain analysis. CITP and MMP1 were measured in peripheral blood. RESULTS: All participants had normal diastolic function according to guidelines. Peak left atrial strain in the reservoir phase (LASr) was significantly reduced in the MFS cohort compared to controls (32.2 ± 9.4 vs 43.9 ± 7.0%; p < 0.001). Serum CITP and CITP:MMP1 ratio were lower among MFS patients, showing significant correlations with LASr (R = 0.311; p = 0.020 and R = 0.437; p = 0.001, respectively). The MFS cohort was divided into quartiles of LASr. MFS patients in the lowest quartile of LASr (<26%) had significantly lower values of CITP:MMP1 ratio compared to the other quartiles. CONCLUSIONS: The analysis of serum biomarkers revealed the presence of increased CCL in association with reduced LASr in the MFS cohort. Our results suggest that excessive CCL may play a role in the development of primary myocardial impairment in these patients. Future studies are needed to confirm our findings and evaluate the prognostic role of CCL markers in the MFS population.

C-Reactive Protein Is Associated with Physical Fitness in Breast Cancer Survivors.

Background: Physical fitness (PF) is an expression of the physiological functioning of multiple body components. PF is an important prognostic factor in terms of cardiovascular mortality, cancer mortality, and all-cause mortality. PF has been related to some biomarkers in the general population but not in breast cancer survivors (BCS). Purpose: To evaluate the effects of PF on biomarkers potentially related to physical activity (PA) in a sample of BCS. Methods: Cross-sectional study. A total of 84 BCS (mean age 54) who had finished their treatment were recruited. Different components of PF were evaluated, namely body composition (anthropometry), cardiorespiratory fitness (one-mile walk test), muscular (handgrip and sit-to-stand timed test), and motor (gait speed) components. Sexual hormones, inflammation, and insulin resistance biomarkers were measured. Results: C-Reactive Protein (CRP) was associated with every component of physical fitness: cardiorespiratory fitness (p-value = 0.002), muscular (sit-to-stand timed test, p-value = 0.002) and motor (gait speed, p-value = 0.004) components, and body composition (body mass index, p-value = 0.003; waist, p-value < 0.000; and waist-to-hip index, p-value = 0.012). CRP also was associated with "poor physical condition," a constructed variable that encompasses all components of physical fitness (p-value < 0.001). Insulin was associated with cardiorespiratory fitness and gait speed (p-values = 0.002 and 0.024, respectively). Insulin-like Growth Factor-1 was negatively associated with waist perimeter and waist-to-hip ratio. Conclusions: CRP can also be considered an indicator of poor PF in BCS. Implications for cancer survivors: in case of elevation of CRP indicating cardiovascular risk, health professionals should recommend lifestyle changes to improve BCS physical condition.

CSF Chitinase 3-Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis.

OBJECTIVE: This study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS). METHODS: CSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical trial with interferon beta. Patients were classified into high and low disability progression phenotypes according to numeric progression rates (NPR) and step-based progression rates (SPR) after a mean follow-up time of 12 years. Protein abundance was measured by shotgun proteomics. Selected proteins from the discovery cohort were quantified by parallel reaction monitoring in CSF samples from an independent validation cohort of 41 patients with progressive MS classified also into high and low disability progression phenotypes after a mean follow-up time of 7 years. RESULTS: Of 2,548 CSF proteins identified in the discovery cohort, 10 were selected for validation based on their association with long-term disability progression: SPATS2-like protein, chitinase 3-like 2 (CHI3L2), plasma serine protease inhibitor, metallothionein-3, phospholipase D4, beta-hexosaminidase, neurexophilin-1, adipocyte enhancer-binding protein 1, cathepsin L1, and lipopolysaccharide-binding protein. Only CHI3L2 was validated, and patients with high disability progression exhibited significantly higher CSF protein levels compared with patients with low disability progression (p = 0.03 for NPR and p = 0.02 for SPR). CHI3L2 levels showed good performance to discriminate between high and low disability progression in patients with progressive MS (area under the curve 0.73; sensitivity 90% and specificity 63%). CONCLUSIONS: Although further confirmatory studies are needed, we propose CSF CHI3L2 as a prognostic protein biomarker associated with long-term disability progression in patients with progressive MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that high CSF CHI3L2 levels identified higher disability progression in patients with progressive MS.

Variación del perfil lipídico durante el embarazo y su relación con las enfermedades metabólicas / Changes in lipid profile during pregnancy and their association with metabolic disorders

Introducción: En el embarazo se producen numerosos cambios fisiológicos en las gestantes los cuales pueden llegar a desencadenar potenciales complicaciones y enfermedades cardiovasculares o metabólicas tales como hipertensión gestacional, hiperlipidemia y diabetes mellitus gestacional.Objetivo: Realizar una revisión sistemática de la literatura con objeto de evaluar la relación entre las variaciones del perfil lipídico durante el embarazo y el riesgo de padecer enfermedades metabólicas y cardiovasculares.Métodos: Se ha llevado a cabo una revisión sistemática siguiendo las directrices del modelo PRISMA en la que se incluyeron 22 artículos. Los descriptores empleados incluyeron marcadores del perfil lipídico (HDL, LDL, TG y CT) y las principales patologías metabólicas y cardiovasculares. El idioma se restringió a español e inglés. La revisión fue llevada a cabo durante el año 2019.Resultados: Niveles elevados de colesterol total, LDL y triglicéridos durante el embarazo se asocian con un mayor riesgo de padecer preeclampsia y diabetes mellitus gestacional. Un mayor índice de masa corporal pre gestacional y una mayor ganancia ponderal se relacionan con mayor tasa hiperlipidemia lo cual conlleva a su vez alteraciones vasculares.Conclusiones: Se hace patente la necesidad de reforzar el control preventivo del peso materno trimestral y del perfil lipídico durante la gestación con objeto de prevenir complicaciones del embarazo. Son necesarios estudios centrados en determinados resultados adversos perinatales tales como la macrosomía del recién nacido.(AU)

Background: Various changes occur during pregnancy that, when exacerbated, could progress to metabolic and cardiovascular disorders such as gestational hypertension, hyperlipidemia, and gestational diabetes mellitus.Objective: To conduct a systematic review of the literature that evaluates the association between changes in lipid profile during pregnancy and the risk of developing metabolic and cardiovascular disorders.Methods: We conducted a PRISMA systematic review of scientific databases. A total of 22 articles were finally included. Used search terms consisted of lipid profile biomarkers (HDL, LDL, triglycerides, total cholesterol) in combination with the most important metabolic and cardiovascular disorders. Language was restricted to Spanish and English. The review was conducted during 2019.Results: High levels of total cholesterol, LDL and triglycerides during pregnancy were found to be associated with increased risk of developing preeclampsia and gestational diabetes mellitus. Higher pre-gestational BMI and elevated gestational weight gain were associated with increase rates of hyperlipidemia which is closely related to vascular pathologies.Conclusions: Fostering routine control of maternal weight during all trimesters of gestation and monitoring the lipid profile throughout pregnancy is necessary to prevent pregnancy adverse outcomes. New studies focused on specific perinatal outcomes such as neonatal macrosomia are required.(AU)

Effects of physical activity on quality of life in overweight and obese children / Efectos de la actividad física sobre la calidad de vida en niños con sobrepeso y obesidad

Background: in recent years the prevalence of obesity in infants, children, and adolescents has increased alarmingly, which may affect their health, educational level, and quality of life. Objectives: the aim of this study was to determine whether a program with physical activity and nutritional recommendations may improve health-related quality of life (HRQL) in overweight and obese children. Material and methods: the design of this study was that of a randomized clinical trial (RCT). The sample consisted of 54 children with a median age of 10.65 years, all of them overweight or obese. They were divided into a study (SG) and a control (CG) group, with 27 children each. The study group received physical activity and nutritional advice, while the control group only received theoretical-practical sessions on nutrition during 9 months. Families participated in the workshops on nutritional recommendations in both groups. Results: there was a significant difference in fat percentage before and after the intervention in the study group compared to the children who did not engage in sports activity. In the SF-10 quality-of-life perception questionnaire, statistically significant differences in both the physical and mental components may be seen at the end of the study between both groups (p < 0.001). Conclusions: an educational intervention with physical activity based on play and nutritional advice improved quality of life in overweight and obese children. Family involvement is vital for children to improve their life habits, and achieve favorable results in the reduction of overweight and obesity. (AU)

Introducción: en los últimos años, la prevalencia de la obesidad en los bebés, niños y adolescentes ha aumentado de forma alarmante, lo que podría afectar a su salud, nivel educativo y calidad de vida. Objetivos: el objetivo de este estudio fue determinar si un programa con actividad física y recomendaciones nutricionales puede mejorar la calidad de vida relacionada con la salud (CVRS) en niños con sobrepeso y obesidad. Material y métodos: el diseño de este estudio fue el de un ensayo clínico aleatorizado (ECA). La muestra consistió en 54 niños de 10,65 años de edad mediana con sobrepeso u obesidad. Se dividieron en grupos de estudio (SG) y de control (CG), ambos con 27 niños. El grupo de estudio recibió actividad física y asesoramiento nutricional mientras que el grupo de control solo recibió las sesiones de nutrición teórico-prácticas durante 9 meses. Las familias participaron en los talleres sobre recomendaciones nutricionales en ambos grupos. Resultados: hubo una diferencia significativa en el porcentaje de grasa antes y después de la intervención en el grupo de estudio en comparación con los niños que no participaron en la actividad deportiva. En el cuestionario de calidad de vida SF-10 se puede observar que existen diferencias estadísticamente significativas en los componentes físicos y mentales al final del estudio entre ambos grupos (p < 0,001). Conclusiones: una intervención educativa con actividad física basada en el juego y asesoramiento nutricional mejoró la calidad de vida de estos niños obesos y con sobrepeso. La participación familiar es vital para que los niños mejoren sus hábitos de vida y logren resultados favorables en la reducción del sobrepeso y la obesidad. (AU)

Effects of physical activity on quality of life in overweight and obese children.

INTRODUCTION: Background: in recent years the prevalence of obesity in infants, children, and adolescents has increased alarmingly, which may affect their health, educational level, and quality of life. Objectives: the aim of this study was to determine whether a program with physical activity and nutritional recommendations may improve health-related quality of life (HRQL) in overweight and obese children. Material and methods: the design of this study was that of a randomized clinical trial (RCT). The sample consisted of 54 children with a median age of 10.65 years, all of them overweight or obese. They were divided into a study (SG) and a control (CG) group, with 27 children each. The study group received physical activity and nutritional advice, while the control group only received theoretical-practical sessions on nutrition during 9 months. Families participated in the workshops on nutritional recommendations in both groups. Results: there was a significant difference in fat percentage before and after the intervention in the study group compared to the children who did not engage in sports activity. In the SF-10 quality-of-life perception questionnaire, statistically significant differences in both the physical and mental components may be seen at the end of the study between both groups (p < 0.001). Conclusions: an educational intervention with physical activity based on play and nutritional advice improved quality of life in overweight and obese children. Family involvement is vital for children to improve their life habits, and achieve favorable results in the reduction of overweight and obesity.

INTRODUCCIÓN: Introducción: en los últimos años, la prevalencia de la obesidad en los bebés, niños y adolescentes ha aumentado de forma alarmante, lo que podría afectar a su salud, nivel educativo y calidad de vida. Objetivos: el objetivo de este estudio fue determinar si un programa con actividad física y recomendaciones nutricionales puede mejorar la calidad de vida relacionada con la salud (CVRS) en niños con sobrepeso y obesidad. Material y métodos: el diseño de este estudio fue el de un ensayo clínico aleatorizado (ECA). La muestra consistió en 54 niños de 10,65 años de edad mediana con sobrepeso u obesidad. Se dividieron en grupos de estudio (SG) y de control (CG), ambos con 27 niños. El grupo de estudio recibió actividad física y asesoramiento nutricional mientras que el grupo de control solo recibió las sesiones de nutrición teórico-prácticas durante 9 meses. Las familias participaron en los talleres sobre recomendaciones nutricionales en ambos grupos. Resultados: hubo una diferencia significativa en el porcentaje de grasa antes y después de la intervención en el grupo de estudio en comparación con los niños que no participaron en la actividad deportiva. En el cuestionario de calidad de vida SF-10 se puede observar que existen diferencias estadísticamente significativas en los componentes físicos y mentales al final del estudio entre ambos grupos (p < 0,001). Conclusiones: una intervención educativa con actividad física basada en el juego y asesoramiento nutricional mejoró la calidad de vida de estos niños obesos y con sobrepeso. La participación familiar es vital para que los niños mejoren sus hábitos de vida y logren resultados favorables en la reducción del sobrepeso y la obesidad.

Childhood Obesity and its Influence on Sleep Disorders: Kids-Play Study.

Background: Sleep disorders are associated with overweight and obese children, and could decrease life quality with limitations to normal daily activities. The purpose of the study is to describe the prevalence of sleep disorders in a cohort of overweight/obese children using respiratory polygraphy. Methods: A descriptive cross-sectional study was conducted in Granada (Spain) on a sample of 98 children with overweight or obesity. The presence of sleep disorders was determined by respiratory polygraphy. Results: Regarding apnoea-hypopnea-index (AHI) results, 44% of affected children had severe sleep apnoea-hypopnea syndrome (SAHS), and the remaining 56% had a mild form of the disorder. With respect to oxygen-desaturation index, 56% of the same group had severe SAHS, 32% had mild SAHS, and the remaining 12% did not suffer from SAHS. Among participants, average scores of 13.8 obstructive apnoea, 7.7 central apnoea, and 13.6 hypopnoea were recorded. Conclusions: Respiratory polygraphy can provide conclusive results in the diagnosis of SAHS in overweight/obese children. Interventional programmes designed and implemented to reduce overweight and obesity can improve quality of sleep and life in children.

Serum endocannabinoid levels in suicide attempters: A pilot study.

The search for a biomarker for suicide risk is a longstanding pursuit in clinical psychiatry. Literature addressing the role of endocannabinoids in suicide attempters (SA) is sparse. This cross-sectional study is aimed at comparing 8 AM serum concentrations of 4 endogenous cannabinoids (anandamide, AEA; 2-arachidonoylglycerol, 2-AG; N-palmitoiletanolamida, PEA; and oleoylethanolamide, OEA) in 30 suicide attempters (SA) and 12 psychiatric controls (PC). 8 AM AEA and PEA serum levels were higher in SA compared to PC without controlling for cannabis use (n = 42) (3.58 ± 5.77 vs. 1.62 ± 2.49, F = 3.04, P = 0.089; and 3.31 ± 4.82 vs. 1.21 ± 1.20, F = 6.22, p = 0.017, respectively). Serum ACTH was higher in PC compared to SA (32.11 ± 21.60 vs. 20.05 ± 9.96, F = 9.031, p = 0.0.005). After controlling for cannabis use in the urine test (n = 28), 8 AM AEA and PEA serum levels remained higher in SA compared to PC (4.57 ± 6.38 vs. 0.64 ± 1.11, F = 4.852, P = 0.037; and 4.35 ± 5.46 vs. 1.21 ± 1.25, F = 4.125, p = 0.053, respectively). The present study offers preliminary evidence about the role of AEA and PEA in suicidal behavior (SB). Furthermore, in the context of the mental pain model of SB, our findings suggest that some endocannabinoids may play a role in the pathophysiology of SB. Our pilot study deserves replication by other studies with bigger sample sizes.