Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumor.

Cancer stem cells (CSCs) in colorectal cancer (CRC) drive intratumoral heterogeneity and distant metastases. Previous research from our group showed that CSCs can be easily detected by autofluorescence (AF). The aim of the present study was to evaluate the potential role of AF CSCs as a prognostic biomarker for CRC relapse. Seventy-five freshly-resected tumors were analyzed, by flow cytometry. AF was categorized as high (H-AF) or low (L-AF), and results were correlated with histological features (grade of differentiation, presence of metastases in lymph nodes (LN), perivascular and lymphovascular invasion) and clinical variables (time to relapse and overall survival). Nineteen out of 75 (25.3%) patients experienced relapse (local or distant), 13 out of these 19 patients showed positive LNs and 6 patients had H-AF. Of note, 4 of them died before 5 years. While patients with H-AF CSCs percentages in the global population experienced 1.5 times increased relapse -HR 1.47, CI 95% (0.60 - 3.63), patients with H-AF CSC percentages and LN metastases had the highest risk of relapse; HR 7.92, p< 0.004, CI 95% (1.97 - 31.82). These data support AF as an accurate and feasible marker to identify CSCs in resected CRC. A strong statistical association between H-AF CSCs and the risk of relapse was observed, particularly in patients with positive LNs, suggesting that H-AF patients might benefit from adjuvant chemotherapy regimens and intensive surveillance due to their high propensity to experience disease recurrence.

Ion-Fluid Transport-Control Feedback along Nanopore Networks.

Biological signaling correlates with the interrelation between ion and nanofluidic transportation pathways. However, artificial embodies with reconfigurable ion-fluid transport interaction aspects remain largely elusive. Herein, we unveiled an intimate interplay between nanopore-driven advancing flow and ion carriage for the spontaneous imbibition of aqueous solutions at the nanoporous thin film level. Ionic factors dominate transport phenomena processing and integration (ions influence fluid motion, which in turn governs the self-regulated ion traveling). We show an ion-induced translation effect that finely converts a chemical input, the nature of ions, into a related fluidic output: modulation of the extent of imbibition. We further find complex imbibition dynamics induced by the ion type and population. We peculiarly pinpoint a stop-and-go effective transport process with a programmable delay time triggered by selective guest-host interactions. The ion-fluid transport interplay is captured by a simple model that considers the counterbalance between the capillary infiltration and solution concentration, owing to water loss at the nanoporous film-air interface. Our results demonstrate that nanopore networks present fresh scenarios for understanding and controlling autonomous macroscopic liquid locomotion and offer a distinctive working principle for smart ion operation.

Standardization of the definition of the types of oncological colectomy. Delphi method for consensus of experts of the Spanish Association of Surgeons.

There is no international consensus on the definition of the type of oncological resection that corresponds to each of the colectomies existing in the current literature. The objective is to define for each colectomy described in the literature: embryological dissection plane, vascular pedicles in which to perform central ligation, the extent of the colectomy, and the need for resection of the greater momentum. A consensus of experts is carried out through the Delphi methodology through two rounds from the Coloproctology Section of the Spanish Association of Surgeons. Study period: November 2021-January 2023. 120 experts were surveyed. Degrees of consensus: Very strong: >90%, Strong: 80%-90%, Moderate: 50%-80%, No consensus: <50%. The definition for each oncological colectomy was established by very strong, and strong recommendations. Each oncological colectomy was established as Right hemicolectomy (RHC), RHC with D3 lymphadenectomy, Extended-RHC, transverse colon segmental colectomy, splenic flexure segmental colectomy, subtotal colectomy, total colectomy, left hemicolectomy (LHC), extended-LHC, sigmoidectomy.

Hepatectomía derecha de urgencia por necrosis hepática infectada secundaria a colangiografía endoscópica / Urgent right hepatectomy for infected hepatic necrosis secondary to endoscopic cholangiography

RESUMEN El hematoma subcapsular hepático es una complicación infrecuente pero potencialmente grave de la colangiografía retrógrada endoscópica. Por otra parte, las complicaciones derivadas del hematoma pueden ser su rotura, con el consiguiente sangrado masivo, y/o la trombosis portal por compresión que evolucione hacia la necrosis, la cual es susceptible de infecciones generalmente graves que requieren un manejo más enérgico. Presentamos el caso de una paciente a quien se le realizó una colangiografía endoscópica retrógrada por una colangitis aguda, y presentó en la evolución un hematoma subcapsular, que progresó a la necrosis hepática por compresión del pedículo portal, y una infección de esa necrosis, por lo que requirió una hepatectomía derecha de urgencia.

ABSTRACT Hepatic subcapsular hematoma is a rare but potentially lethal complication of endoscopic retrograde cholangiography. On the other hand, complications derived from the hematoma can be its rupture with the consequent massive bleeding, and/or portal thrombosis due to compression that evolves towards necrosis, which is susceptible to generally serious infections that require more aggressive management. We present the case of a patient treated in our department who underwent retrograde endoscopic cholangiography as treatment for her acute cholangitis, presenting in the evolution a subcapsular hematoma that progressed to hepatic necrosis due to compression of the portal pedicle and later an infection of that necrosis. requiring an emergency right hepatectomy as surgical treatment.

Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Exceptional diversity of KIR and HLA class I in Egypt.

Genetically determined variation of killer cell immunoglobulin like receptors (KIR) and their HLA class I ligands affects multiple aspects of human health. Their extreme diversity is generated through complex interplay of natural selection for pathogen resistance and reproductive health, combined with demographic structure and dispersal. Despite significant importance to multiple health conditions of differential effect across populations, the nature and extent of immunogenetic diversity is under-studied for many geographic regions. Here, we describe the first high-resolution analysis of KIR and HLA class I combinatorial diversity in Northern Africa. Analysis of 125 healthy unrelated individuals from Cairo in Egypt yielded 186 KIR alleles arranged in 146 distinct centromeric and 79 distinct telomeric haplotypes. The most frequent haplotypes observed were KIR-A, encoding two inhibitory receptors specific for HLA-C, two that are specific for HLA-A and -B, and no activating receptors. Together with 141 alleles of HLA class I, 75 of which encode a KIR ligand, we identified a mean of six distinct interacting pairs of inhibitory KIR and HLA allotypes per individual. We additionally characterize 16 KIR alleles newly identified in the study population. Our findings place Egyptians as one of the most highly diverse populations worldwide, with important implications for transplant matching and studies of immune-mediated diseases.

Single-cell transcriptomic profiling reveals a pathogenic role of cytotoxic CD4+ T cells in giant cell arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis mediated by an aberrant immunological response against the blood vessel wall. Although the pathogenic mechanisms that drive GCA have not yet been elucidated, there is strong evidence that CD4+ T cells are key drivers of the inflammatory process occurring in this vasculitis. The aim of this study was to further delineate the role of CD4+ T cells in GCA by applying single-cell RNA sequencing and T cell receptor (TCR) repertoire profiling to 114.799 circulating CD4+ T cells from eight GCA patients in two different clinical states, active and in remission, and eight healthy controls. Our results revealed an expansion of cytotoxic CD4+ T lymphocytes (CTLs) in active GCA patients, which expressed higher levels of cytotoxic and chemotactic genes when compared to patients in remission and controls. Accordingly, differentially expressed genes in CTLs of active patients were enriched in pathways related to granzyme-mediated apoptosis, inflammation, and the recruitment of different immune cells, suggesting a role of this cell type in the inflammatory and vascular remodelling processes occurring in GCA. CTLs also exhibited a higher clonal expansion in active patients with respect to those in remission. Drug repurposing analysis prioritized maraviroc, which targeted CTLs, as potentially repositionable for this vasculitis. In addition, effector regulatory T cells (Tregs) were decreased in GCA and showed lower expression of genes involved in their suppressive activity. These findings provide further insights into the pathogenic role of CD4+ T cells in GCA and suggest targeting CTLs as a potential therapeutic option.

High-resolution DNA methylation screening of the major histocompatibility complex in multiple sclerosis.

Background: The HLA-DRB1 gene in the major histocompatibility complex (MHC) region in chromosome 6p21 is the strongest genetic factor identified as influencing multiple sclerosis (MS) susceptibility. DNA methylation changes associated with MS have been consistently detected at the MHC region. However, understanding the full scope of epigenetic regulations of the MHC remains incomplete, due in part to the limited coverage of this region by standard whole genome bisulfite sequencing or array-based methods. Methods: We developed and validated an MHC capture protocol coupled with bisulfite sequencing and conducted a comprehensive analysis of the MHC methylation landscape in blood samples from 147 treatment naïve MS study participants and 129 healthy controls. Results: We identified 132 differentially methylated region (DMRs) within MHC region associated with disease status. The DMRs overlapped with established MS risk loci. Integration of the MHC methylome with human leukocyte antigen (HLA) genetic data indicate that the methylation changes are significantly associated with HLA genotypes. Using DNA methylation quantitative trait loci (mQTL) mapping and the causal inference test (CIT), we identified 643 cis-mQTL-DMRs paired associations, including 71 DMRs possibly mediating causal relationships between 55 single nucleotide polymorphisms (SNPs) and MS risk. Results: The results describe MS-associated methylation changes in MHC region and highlight the association between HLA genotypes and methylation changes. Results from the mQTL and CIT analyses provide evidence linking MHC region variations, methylation changes, and disease risk for MS.

Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study.

Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using the two-sample Mendelian randomization approach, with the genome-wide association study data for both LTL and SSc. The results of inverse-variance weighted regression (OR = 0.716 [95% CI 0.528-0.970], p = 0.031) and the Mendelian randomization pleiotropy residual sum and outlier method (OR = 0.716 [95% CI 0.563-0.911], p = 0.035) indicate an association between telomere length and SSc. Specifically, longer genetically predicted LTL is associated with a reduced risk of SSc. Sensitivity tests highlight the significant roles of the variants rs10936599 and rs2736100 annotated to the TERC and TERT genes, respectively. Our findings suggest an influence of telomere length in leukocytes on the development of SSc.

Non-classical circulating monocytes expressing high levels of microsomal prostaglandin E2 synthase-1 tag an aberrant IFN-response in systemic sclerosis.

Systemic sclerosis (SSc) is a complex disease that affects the connective tissue, causing fibrosis. SSc patients show altered immune cell composition and activation in the peripheral blood (PB). PB monocytes (Mos) are recruited into tissues where they differentiate into macrophages, which are directly involved in fibrosis. To understand the role of CD14+ PB Mos in SSc, a single-cell transcriptome analysis (scRNA-seq) was conducted on 8 SSc patients and 8 controls. Using unsupervised clustering methods, CD14+ cells were assigned to 11 clusters, which added granularity to the known monocyte subsets: classical (cMos), intermediate (iMos) and non-classical Mos (ncMos) or type 2 dendritic cells. NcMos were significantly overrepresented in SSc patients and showed an active IFN-signature and increased expression levels of PTGES, in addition to monocyte motility and adhesion markers. We identified a SSc-related cluster of IRF7+ STAT1+ iMos with an aberrant IFN-response. Finally, a depletion of M2 polarised cMos in SSc was observed. Our results highlighted the potential of PB Mos as biomarkers for SSc and provided new possibilities for putative drug targets for modulating the innate immune response in SSc.

[Pseudoascitis by giant ovaric cyst] / Pseudoascitis por quiste ovárico gigante.

The term pseudoascitis is used in patients who give the false impression of ascites, with abdominal distension but without peritoneal free fluid. The case of a 66-year-old woman, hypertensive and hypothyroid with occasional alcohol consumption, who consults due to progressive abdominal distension of 6 months of evolution and diffuse percussion dullness is presented, in whom a paracentesis is performed with the wrong endorsement of examination ultrasound that reports abundant intrabdominal free fluid (Fig. 1), later finding in the CT scan of the abdomen and pelvis an expansive process of cystic appearance of 295mm x 208mm x 250mm. Left anexectomy is programmed (Fig. 2) with pathological report of mucinous ovarian cystadenoma. The case report refers to the availability of the giant ovarian cyst within the differential diagnosis of ascites. If no symptoms or obvious signs of liver, kidney, heart or malignant disease are found and / or ultrasound does not reveal typical signs of intra-abdominal free fluid (fluid in the bottom of the Morrison or Douglas sac, presence of floating free intestinal handles), a CT scan and / or an RMI should be requested before performing paracentesis, which could have potentially serious consequences.

El término pseudoascitis, se utiliza en los pacientes que dan la falsa impresión de ascitis, con distensión abdominal pero sin líquido libre peritoneal. Se presenta el caso de una mujer de 66 años, hipertensa e hipotiroidea con consumo ocasional de alcohol, que consulta por distensión abdominal progresiva de 6 meses de evolución y matidez difusa a la percusión, en quien se realiza una paracentesis con el aval equivoco de examen ecográfico que informa abundante líquido libre  intrabdominal (Fig. 1), hallando posteriormente en TAC de abdomen y pelvis un proceso expansivo de aspecto quístico de 295mm x 208mm x 250mm. Se programa anexectomia izquierda (Fig. 2) con informe anatomopatológico de cistoadenoma mucinoso de ovario. La comunicación del caso remite a tener disponible el quiste ovárico gigante dentro de los diagnósticos diferenciales de ascitis. Si no se hallan síntomas o signos evidentes de insuficiencia hepática, renal, cardiaca o enfermedad maligna y/o la ecografía no revela signos típicos de líquido libre intrabdominal  (líquido en el fondo de saco de Morrison o de Douglas, presencia de asas intestinales libres flotantes), se debería solicitar una TAC y/o una RMI antes de realizar una paracentesis, la cual podría tener consecuencias potencialmente graves.

Identification of Mechanisms by Which Genetic Susceptibility Loci Influence Systemic Sclerosis Risk Using Functional Genomics in Primary T Cells and Monocytes.

OBJECTIVE: Systemic sclerosis (SSc) is a complex autoimmune disease with a strong genetic component. However, most of the genes associated with the disease are still unknown because associated variants affect mostly noncoding intergenic elements of the genome. We used functional genomics to translate the genetic findings into a better understanding of the disease. METHODS: Promoter capture Hi-C and RNA-sequencing experiments were performed in CD4+ T cells and CD14+ monocytes from 10 SSc patients and 5 healthy controls to link SSc-associated variants with their target genes, followed by differential expression and differential interaction analyses between cell types. RESULTS: We linked SSc-associated loci to 39 new potential target genes and confirmed 7 previously known SSc-associated genes. We highlight novel causal genes, such as CXCR5, as the most probable candidate gene for the DDX6 locus. Some previously known SSc-associated genes, such as IRF8, STAT4, and CD247, showed cell type-specific interactions. We also identified 15 potential drug targets already in use in other similar immune-mediated diseases that could be repurposed for SSc treatment. Furthermore, we observed that interactions were directly correlated with the expression of important genes implicated in cell type-specific pathways and found evidence that chromatin conformation is associated with genotype. CONCLUSION: Our study revealed potential causal genes for SSc-associated loci, some of them acting in a cell type-specific manner, suggesting novel biologic mechanisms that might mediate SSc pathogenesis.

Validación de la resonancia magnética pélvica como método de elección para determinar la distancia al margen anal en el cáncer de recto / Validation of pelvic magnetic resonance imaging as the method of choice to determine the distance to the anal margin in rectal cancer

Introducción: La altura exacta del tumor en el recto y sus relaciones anatómicas contribuyen a determinar la estrategia terapéutica multidisciplinar basada en la combinación de radio-quimioterapia y cirugía radical. Nuestro objetivo es valorar cuál es el método diagnóstico más preciso en la medición preoperatoria de la distancia al margen anal, y si la resonancia magnética pélvica (RM) puede sustituir a los métodos instrumentales clásicos. Métodos: Estudio prospectivo de precisión diagnóstica entre colonoscopia (CF), rectoscopia rígida (RRp) y RM en pacientes con indicación de cirugía radical. La RRp intraoperatoria fue considerada la prueba de referencia. Se analizaron las correlaciones entre las distintas técnicas y su coeficiente de determinación, así como el coeficiente de correlación intraclase y el grado de acuerdo entre los distintos test. Resultados: Se incluyeron 96 pacientes con edad media (DE) de 68 (14,1) años y predominio de varones (65%). Un 72% recibió tratamiento neoadyuvante. La distancia media al margen anal, medida mediante CF=103,5mm, fue significativamente mayor al resto, que obtuvieron valores similares: RRp=81,1, RM=77,4, RRp intraoperatoria=82,9mm (p<0,001). Se objetivó una significativa correlación intraclase y hubo un elevado acuerdo entre todas las mediciones pre e intraoperatorias a excepción de la realizada mediante CF, que sobreestimó el resultado. La RM aportó información más individualizada y precisa. Conclusiones: Existe variabilidad entre los métodos de medición, siendo la colonoscopia el menos fiable. La RM ofrece valores objetivos, comparables, precisos e individualizados que pueden sustituir a los obtenidos por RR en tumores de cualquier localización del recto. (AU)

Introduction: Distance from anal verge of rectal tumors and their anatomical relationships contribute to determine the multidisciplinary therapeutic strategy based on the combination of radio-chemotherapy and radical surgery. Our aims are to investigate which is the most accurate method for the preoperative measuring of the distance from the anal verge in rectal tumors and if the pelvic MRI can substitute the classical instrumental methods. Methods: Prospective study of diagnostic precision between flexible colonoscopy (FC), preoperative rigid rectosigmoidoscopy (pRR) and pelvic MRI in patients scheduled to radical surgery. Rigid intraoperative rectoscopy (iRR) was considered the reference test. The correlations between the different techniques and their determination coefficient as well as the intraclass correlation coefficient and the degree of agreement between the different tests were analyzed. Results: 96 patients (65% males), mean age (SD): 68 (14.1) years were included. 72% received neoadjuvant treatment. The mean distance to the anal margin measured by FC=103.5mm, was significantly greater than others, which had similar values: pRR=81.1; MRI=77.4; iRR=82.9mm (P<.001). A significant intraclass correlation was observed and there was high agreement between all pre- and intraoperative measurements except for the performed by FC, which overestimated the results. MRI provided more individualized and accurate information. Conclusions: There is variability between the measurement methods, being colonoscopy the least reliable. MRI offers objective, comparable, accurate and individualized values that can replace those obtained by pRR for tumors of any location in the rectum. (AU)

The Effect of Body Fat Distribution on Systemic Sclerosis.

Obesity contributes to a chronic proinflammatory state, which is a known risk factor to develop immune-mediated diseases. However, its role in systemic sclerosis (SSc) remains to be elucidated. Therefore, we conducted a two-sample mendelian randomization (2SMR) study to analyze the effect of three body fat distribution parameters in SSc. As instrumental variables, we used the allele effects described for single nucleotide polymorphisms (SNPs) in different genome-wide association studies (GWAS) for SSc, body mass index (BMI), waist-to-hip ratio (WHR) and WHR adjusted for BMI (WHRadjBMI). We performed local (pHESS) and genome-wide (LDSC) genetic correlation analyses between each of the traits and SSc and we applied several Mendelian randomization (MR) methods (i.e., random effects inverse-variance weight, MR-Egger regression, MR pleiotropy residual sum and outlier method and a multivariable model). Our results show no genetic correlation or causal relationship between any of these traits and SSc. Nevertheless, we observed a negative causal association between WHRadjBMI and SSc, which might be due to the effect of gastrointestinal complications suffered by the majority of SSc patients. In conclusion, reverse causality might be an especially difficult confounding factor to define the effect of obesity in the onset of SSc.

Validation of pelvic magnetic resonance imaging as the method of choice to determine the distance to the anal margin in rectal cancer.

INTRODUCTION: Distance from anal verge of rectal tumours and their anatomical relationships contribute to determine the multidisciplinary therapeutic strategy based on the combination of radio-chemotherapy and radical surgery. Our aims are to investigate which is the most accurate method for the preoperative measuring of the distance from the anal verge in rectal tumours and if the pelvic MRI can substitute the classical instrumental methods. METHODS: Prospective study of diagnostic precision between flexible colonoscopy (FC), preoperative rigid rectosigmoidoscopy (pRR) and pelvic MRI in patients scheduled to radical surgery. Rigid intraoperative rectoscopy (iRR) was considered the reference test. The correlations between the different techniques and their determination coefficient as well as the intraclass correlation coefficient and the degree of agreement between the different tests were analyzed. RESULTS: 96 patients (65% males), mean age (SD): 68 (14.1) years were included. 72% received neoadjuvant treatment. The mean distance to the anal margin measured by FC = 103.5 mm, was significantly greater than others, which had similar values: pRR = 81.1; MRI = 77.4; iRR = 82.9 mm (P < .001). A significant intraclass correlation was observed and there was high agreement between all pre- and intraoperative measurements except for the performed by FC, which overestimated the results. MRI provided more individualized and accurate information. CONCLUSIONS: There is variability between the measurement methods, being colonoscopy the least reliable. MRI offers objective, comparable, accurate and individualized values that can replace those obtained by pRR for tumours of any location in the rectum.

Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy.

The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk.

Recent advances in elucidating the genetic basis of systemic sclerosis.

PURPOSE OF REVIEW: Systemic sclerosis (SSc) is a complex autoimmune disorder that affects the connective tissue and causes severe vascular damage and fibrosis of the skin and internal organs. There are recent advances in the field that apply novel methods to high throughput genotype information of thousands of patients with SSc and provide promising results towards the use of genomic data to help SSc diagnosis and clinical care. RECENT FINDINGS: This review addresses the development of the first SSc genomic risk score, which can contribute to differentiating SSc patients from healthy controls and other immune-mediated diseases. Moreover, we explore the implementation of data mining strategies on the results of genome-wide association studies to highlight subtype-specific HLA class II associations and a strong association of the HLA class I locus with SSc for the first time. Finally, the combination of genomic data with transcriptomics informed drug repurposing and genetic association studies in well characterized SSc patient cohorts identified markers of severe complications of the disease. SUMMARY: Early diagnosis and clinical management of SSc and SSc-related complications are still challenging for rheumatologists. The development of predictive models and tools using genotype data may help to finally deliver personalized clinical care and treatment for patients with SSc in the near future.

R-Ras1 and R-Ras2 Expression in Anatomical Regions and Cell Types of the Central Nervous System.

Since the optic nerve is one of the most myelinated tracts in the central nervous system (CNS), many myelin diseases affect the visual system. In this sense, our laboratory has recently reported that the GTPases R-Ras1 and R-Ras2 are essential for oligodendrocyte survival and maturation. Hypomyelination produced by the absence of one or both proteins triggers axonal degeneration and loss of visual and motor function. However, little is known about R-Ras specificity and other possible roles that they could play in the CNS. In this work, we describe how a lack of R-Ras1 and/or R-Ras2 could not be compensated by increased expression of the closely related R-Ras3 or classical Ras. We further studied R-Ras1 and R-Ras2 expression within different CNS anatomical regions, finding that both were more abundant in less-myelinated regions, suggesting their expression in non-oligodendroglial cells. Finally, using confocal immunostaining colocalization, we report for the first time that R-Ras2 is specifically expressed in neurons. Neither microglia nor astrocytes expressed R-Ras1 or R-Ras2. These results open a new avenue for the study of neuronal R-Ras2's contribution to the process of myelination.