APARICIÓN TEMPRANA DEL PATRÓN DE DOLOR CRÓNICO EN PACIENTES MUSCULOESQUELÉTICOS SUBAGUDOS

The chronic pain pattern implies high levels of negative emotions, pain and perceived disability disability perceived. Up to date few studies have assessed when this chronic pain pattern appears. This study is aimed at exploring this issue. Methods: were evaluated  146 subjects with 4 weeks sick leave due to musculoskeletal diseases (MSDs) and 95 with Rheumatoid Arthritis (RA). All patients completed the following assessment instruments: the Sadness and Depression Questionnaire (CTD), Anxiety situations and responses. Inventory –Brief form- (ISRA-B), Health Assessment Questionnaire (HAQ), a visual analogy scale for intensity of pain and a likert type scale for the frequency of pain. The analyses included a comparison on the scores of the tests between patients on sick leave due to MD compared to RA patients. Descriptive and bivariate analyses were performed. Results: Patients on sick leave due to MD and RA patients reported similar perception of their disability, showing a high HAQ score mean. Patients on sick leave due to MD reported more perceived frequency and intensity of pain than RA patients. In relation to negative emotions, both groups reported similar high levels with some poorer levels for RA patients compared to patients on sick leave due to MD for cognitive, evaluation and life situations anxiety. Depression scores presented the same levels for both patients groups. Conclusions: Our study shows that patients with subacute pain/disability and chronic pain/disability report very similar pattern for negative emotions and perception of pain and disability, suggesting that these factors appear in an early stage and contributing to the transition from acute to chronic pain/disability.El patrón de dolor crónico implica altos niveles de emociones negativas, dolor y discapacidad percibida. Pocos estudios han evaluado el patrón de aparición del dolor crónico  y éste era nuestro objetivo. Método: fueron evaluados 146 participantes con 4 semanas la Baja Laboral por enfermedades musculoesqueléticas (DsMS) y 95 con artritis reumatoide (AR) mediante los siguientes instrumentos: el Cuestionario de Tristeza y Depresión (CTD), el  Inventario de Situaciones y Respuestas de Ansiedad–forma breve-. (ISRA-B), Cuestionario de Evaluación de Salud (HAQ), una escala analógica visual para la intensidad del dolor y una escala tipo Likert para la frecuencia del dolor. Los análisis (descriptivos y bivariados) incluyeron una comparación de las puntuaciones de las pruebas entre los pacientes con baja laboral por EM en comparación con los pacientes con AR.  Resultados: Los pacientes con Baja Laboral por enfermedades musculoesqueléticas y los pacientes con AR informaron de una percepción similarde su discapacidad, según el HAQ. Pacientes con Baja Laboral por enfermedades musculoesqueléticas informaron mayor frecuencia percibida y más intensidad de dolor que los pacientes con AR. En relación a las emociones negativas, ambos grupos presentaron niveles altos y similares, con algunos niveles más pobres de los pacientes con AR en comparación con Pacientes con Baja Laboral por enfermedades musculoesqueléticas para la ansiedad cognitiva, la ansiedad de evaluación y la de la vida cotidiana (en  ISRA-B). Las puntuaciones en depresión presentan los mismos niveles en ambos grupos de pacientes.Conclusión. Nuestro estudio muestra que los pacientes con dolor subagudo/discapacidad y dolor crónico/discapacidad reportan un patrón muy similar para las emociones negativas y la percepción del dolor y la discapacidad, lo que sugiere que estos factores aparecen en una etapa temprana y favorecen, por tanto, la transición de dolor agudo a crónico/discapacidad

Synthesis, characterization and self aggregation of a new neo-pentylamide cholic derivative (Na-n-penC)

The 10th International Electronic Conference on Synthetic Organic Chemistry session Supramolecular ChemistryThe self-aggregation in aqueous solution of a new neo-pentyl amide of the 3-β-amino derivative of cholic acid (Na-n-penC) has been investigated in aqueous solution by surface tension and steady state-fluorescence spectroscopy of pyrene (used as a probe). The nature of the agregates was determined by transmission electron microscopy (TEM) revealing that vesicles are formed. The structure of the compound in the solid state was resolved by X-ray spectroscopy. The synthesis of the compound is also give

473 DIFFERENTIAL PROTEOME OF ARTICULAR CHONDROCYTES FROM PATIENTS WITH OSTEOARTHRITIS

Cartilage damage is a major problem in osteoarthritis (OA). To gain insight into the pathogenesis of OA, we have analyzed the differential proteome of articular chondrocytes from these patients. Protein extracts were prepared from cultured chondrocytes from 6 patients with end-stage OA and 6 normal donors and were analyzed by 2D-DIGE. Differentially expressed proteins were identified by mass spectrometry (MS). Significant differential expression was observed for 27 proteins, with 14 underexpressed and 13 overexpressed chondrocyte OA proteins. Of special interest was the identification of destrin, cofilins, gelsolin, annexin A2, glycolytic enzymes, chaperones, cathepsin D, proteasome beta 9 subunit isoform 2 proprotein and proteasome activator hPA28 subunit beta. The altered expression of these proteins is consistent with events such as cytoskeleton binding, protein disruption, apoptosis, and glycolysis, demonstrating the ability of the 2D-DIGE/MS platform to identify proteins with altered expression in chondrocytes from patients with end-stage OA. The identification of these proteins may open new lines of research for this disease.S

Crystal Structure of a Head-to-Head Bis(cholic)-Urea Dimer

The 18th International Electronic Conference on Synthetic Organic Chemistry session General Organic SynthesisA head-to-head dimer of cholic acid linked at C3 carbon atoms by a urea bridge was synthesized and the crystal structure was studied. The crystal belongs to the monoclinic crystal system, space group I2. The packing shows a bilayer structure with alternating hydrophobic and hydrophilic layers. The horizontal and vertical planes of the two cholic residues are almost parallel to each other, the vertical ones being perpendicular to the bilayers. The hydrogen bond network is two-dimensional as it does not propagate in the direction perpendicular to the bilayers. It is noteworthy that the nitrogen atoms of the urea bridge do not participate in that network. The carbonyl urea group and only one of the ester of the two side chains form hydrogen bonds with two other dimers through the steroid hydroxy O7-H and O12-H groups. This means that each dimer forms eight hydrogen bonds but only four are differen

Highly Hydrophilic and Lipophilic Derivatives of Bile Salts

Lipophilicity of 15 derivatives of sodium cholate, defined by the octan-1-ol/water partition coefficient (log P), has been theoretically determined by the Virtual log P method. These derivatives bear highly hydrophobic or highly hydrophilic substituents at the C3 position of the steroid nucleus, being linked to it through an amide bond. The difference between the maximum value of log P and the minimum one is enlarged to 3.5. The partition coefficient and the critical micelle concentration (cmc) are tightly related by a double-logarithm relationship (VirtuallogP=−(1.00±0.09)log(cmcmM)+(2.79±0.09)), meaning that the Gibbs free energies for the transfer of a bile anion from water to either a micelle or to octan-1-ol differ by a constant. The equation also means that cmc can be used as a measurement of lipophilicity. The demicellization of the aggregates formed by three derivatives of sodium cholate bearing bulky hydrophobic substituents has been studied by surface tension and isothermal titration calorimetry. Aggregation numbers, enthalpies, free energies, entropies, and heat capacities, ΔCP,demic, were obtained. ΔCP,demic, being positive, means that the interior of the aggregates is hydrophobicThis work was funded by the Ministerio de Ciencia y Tecnología, Spain (Project MAT2017-86109P)S

Post-Hospital Syndrome and Hyponatremia

Introduction: Post-hospital syndrome (PHS) is defined as a period of vulnerability during the first 30 days after a patient is discharged from hospital, in which multiple factors come into play. Hyponatremia is the most frequent hydroelectrolytic disorder in hospitalized patients and may be related to the appearance of PHS. Objective: The objective is to estimate the prevalence of PHS that is assessed as the rate of readmissions in the first 30 days after discharge, in patients with hyponatremia. Material and Methods: It is a descriptive observational study of patients with hyponatremia who were discharged from 1 September 2010 to 2 February 2020 at the Internal Medicine Service of the Hospital University of San Juan (Alicante, Spain). Results: Of the 25 included patients, 5 (20%) were readmitted within a month of discharge, after a mean of 11.4 days (standard deviation [SD] 5.1). The overall mortality of the study was 20% (n = 5), with one case of death in the first 30 days post-hospitalization (4%). In 12 patients (48%) the origin of the hyponatremia was undetermined. The most frequently recorded etiology for the condition was pharmacological (n = 7, 28%), and there was pronounced variability in its clinical and laboratory study. The most widely used corrective measure was drug withdrawal, in 16 patients (64%). Water intake restriction was the most common treatment after discharge (5 patients, 20%), followed by urea (2 patients, 8%), while tolvaptan was not used. Conclusion: Hyponatremia may be the cause of PHS, which could increase the rate of early readmission. Hyponatremia is an underdiagnosed and undertreated entity, so it is necessary to apply an appropriate system to optimize its management and, in future studies, to assess its impact on PHS

A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction

BMP2/BMP4 colorectal cancer susceptibility loci in northern and southern european populations

Genome-wide association studies have successfully identified 20 colorectal cancer susceptibility loci. Amongst these, four of the signals are defined by tagging single nucleotide polymorphisms (SNPs) on regions 14q22.2 (rs4444235 and rs1957636) and 20p12.3 (rs961253 and rs4813802). These markers are located close to two of the genes involved in bone morphogenetic protein (BMP) signaling (BMP4 and BMP2, respectively). By investigating these four SNPs in an initial cohort of Spanish origin, we found substantial evidence that minor allele frequencies (MAFs) may be different in northern and southern European populations. Therefore, we genotyped three additional southern European cohorts comprising a total of 2028 cases and 4273 controls. The meta-analysis results show that only one of the association signals (rs961253) is effectively replicated in the southern European populations, despite adequate power to detect all four. The other three SNPs (rs4444235, rs1957636 and rs4813802) presented discordant results in MAFs and linkage disequilibrium patterns between northern and southern European cohorts. We hypothesize that this lack of replication could be the result of differential tagging of the functional variant in both sets of populations. Were this true, it would have complex consequences in both our ability to understand the nature of the real causative variants, as well as for further study designs

Effect of oral anticoagulants on the outcome of faecal immunochemical test

Background: We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening. Methods: Individuals aged 50-69 years were invited to receive one FIT sample (cutoff 75 ng ml-1) between November 2008 and June 2011. Results: Faecal immunochemical test was positive in 9.3% (21 out of 224) of users of OAC and 6.2% (365 out of 5821) of non-users (P-trend ¼ 0.07). The positive predictive value (PPV) for advanced neoplasia (AN) in non-users was 50.4% vs 47.6% in users (odds ratio, 0.70; 95% CI, 0.3-1.8; P ¼ 0.5). The PPV for AN in OAC more antiplatelets (aspirin or clopidogrel) was 75% (odds ratio, 2; 95% CI, 0.4-10.8; P ¼ 0.4). Conclusions: Oral anticoagulant did not significantly modify the PPV for AN in this population-based colorectal screening program. The detection rate of advanced adenoma was higher in the combination OAC more antiplatelets

Multiple sporadic colorectal cancers display a unique methylation phenotype.

Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity