Expansion of the core features of VACTERL association to include genital anomalies.

Genital anomalies have been reported with VACTERL association but not considered a core feature. Acute and chronic complications stemming from unrecognized genital anomalies have been reported in adolescents and young adults with VACTERL association. We sought to determine the frequency and severity of genital anomalies in VACTERL patients and identify which core features were more frequently associated with genital anomalies. A retrospective chart review from January 2010 to October 2021 identified 211 patients with two or more core VACTERL features, 34% of whom had a genital anomaly. The majority of genital anomalies (83% of those in males and 90% in females) were classified as functionally significant (requiring surgical intervention or causing functional impairment). The frequency of genital anomalies in the VACTERL cohort was higher if anorectal malformations or renal anomalies were present in both males and females and if vertebral anomalies were present in females. Due to their functional significance, genital anomalies should be assessed in all patients with two or more core features of VACTERL association, especially in those with anorectal or renal anomalies. Most genital anomalies in males will be detected on physical examination but additional investigation is often needed to detect genital anomalies in females. The timing and type of investigation are subjects for future study.

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges.

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph-based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly "Question-of-the-Month (QotM) Challenge" series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

Ear anomalies and hearing loss in patients with VACTERL association and the effect of maternal diabetes.

VACTERL association is typically defined as the presence of three components among these birth defects: vertebral anomalies, anal atresia, cardiac anomalies, esophageal atresia/tracheoesophageal fistula (EA/TEF), renal anomalies, and limb defects. There is increasing recognition that VACTERL and other recurrent constellations of embryonic development often overlap clinically and might share pathogenesis. We conducted a comprehensive chart review of a large patient population with VACTERL association from two tertiary care centers in California. We included patients with incomplete VACTERL expression, which we denoted as "partial VACTERL" (pVACTERL). We assessed the occurrence of craniofacial (CF) findings in these two groups and the combined cohort. We collected data on potential risk factors and demographic information such as sex, Hispanic ancestry, pregnancy complications, and maternal age. The study included 409 participants, of whom 263 had VACTERL and 146 pVACTERL. CF abnormalities were found in 17.3% of VACTERL patients and 9.4% of pVACTERL patients. In the VACTERL group, ear anomalies were found in 10.2%, microtia in 5.9%, hearing loss (HL) in 13.90%, and orofacial clefts in 3.1%. In the pVACTERL group, ear anomalies were found in 7.2%, microtia in 5.0%, HL in 9.3%, and orofacial cleft in 2.2%. Maternal diabetes significantly increased the risk for HL in VACTERL (odds ratio [OR]: 3.71, 95% confidence interval [CI]: 1.5-7.3) and pVACTERL patients (OR: 6.7, 95% CI: 1.70-23.4). Poorly controlled maternal diabetes significantly increased the risk for all the outcomes in VACTERL patients including CF anomalies (OR: 4.2, 95% CI: 1.9-9.6), ear anomalies (OR: 4.7, 95% CI: 1.8-11.8), microtia (OR: 5.4, 95% CI: 1.7-16.6), and HL (OR: 8.1, 95% CI: 3.4-19.4). Twin status was significantly associated with the occurrence of microtia (p = 0.038) in VACTERL patients. Occurrence of CF features, particularly ear anomalies, microtia, and HL, might be considered as part of phenotypic diversity of VACTERL association. Diabetes and twinning might appear to play a role in increasing the risk for this phenotype in VACTERL association.

Evaluación fonoaudiológica clínica de la alimentación y la deglución en lactantes menores con hipoplasia 0 aplasia cóndilo-mandibular: Scoping review / Clinical speech therapy evaluation of feeding and swallowing in young infants with hypoplasia or aplasia of the mandibular condyle: A scoping review

Introducción: Los síndromes craneofaciales congénitos han sido ampliamente descritos debido a su naturaleza precursora de alteraciones en el sistema cráneo-cérvico-mandibular; específicamente las malformaciones a nivel cóndilo-mandibular, como la hipoplasia o aplasia de estas estructuras, comprometen una de las funciones vitales para el ser humano: la alimentación. Con el objetivo de establecer una guía de práctica clínica, se proponen lineamientos que promuevan la práctica fonoaudiológica basada en la evidencia. Pacientes y métodos: Se realiza una revisión sistemática de tipo scoping review en las principales bases de datos biomédicas, en búsqueda de artículos científicos dirigidos a la evaluación de la alimentación y deglución en lactantes menores con hipoplasia y aplasia cóndilo-mandibular asociadas a síndromes craneofaciales. Resultados:Se seleccionaron 37 artículos de tipo ensayo clínico aleatorizado, estudio de casos, estudio ecológico, metaanálisis y revisión sistemática, cuyo contenido es presentado y organizado dentro de un formato de evaluación que busca la obtención de información anatomofuncional de los lactantes menores para el desarrollo de su evaluación clínica. Conclusiones: Se resalta una reducida cantidad y difusión de evidencia fonoaudiológica al aplicar los parámetros de búsqueda, encontrando que los criterios de evaluación específicos ante esta patología no difieren en gran medida a los de la población pediátrica en general.(AU)

Introduction: Congenital craniofacial syndromes have been widely described due to their precursor nature of alterations in the cranio-cervico-mandibular system; specifically, condyle-mandibular malformations such as hypoplasia or aplasia of these structures, compromise one of the vital functions for humans, nutrition. In order to establish a clinical practice guide, guidelines that promote evidence-based speech therapy practice are proposed. Patients and methods: A scoping review is carried out in the main biomedical databases, in search of scientific articles aimed at evaluating feeding and swallowing in newborn and young infants with condyle-mandibular hypoplasia and aplasia associated with craniofacial syndromes. Results: Thirty-seven articles of a randomized clinical trial, case study, ecological study, meta-analysis, and systematic review were selected, this content is presented and organized using an evaluation format that seeks to obtain anatomical and functional information on newborn and young infants for the development of a clinical assessment. Conclusions: A reduced amount and dissemination of speech therapy evidence is highlighted when applying the search parameters, finding that the specific evaluation criteria for this pathology do not differ greatly from those of the pediatric population in general.(AU)

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

OBJECTIVES: To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. DESIGN: A single-center prospective cohort study from January to December 2021. SETTING: Twelve medical-surgical PICU beds at a university hospital. PATIENTS: Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. CONCLUSIONS: Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

Biomarkers of Glycocalyx Injury and Endothelial Activation are Associated with Clinical Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Sepsis is one of the main causes of morbidity and mortality worldwide. Microcirculatory impairment, especially damage to the endothelium and glycocalyx, is often not assessed. The objective of this systematic review and meta-analysis was to summarize the available evidence of the risk of unsatisfactory outcomes in patients with sepsis and elevated glycocalyx injury and endothelial activation biomarkers. DESIGN: A systematic search was carried out on PubMed/MEDLINE, Embase, Cochrane and Google Scholar up to December 31, 2021, including studies in adults and children with sepsis which measured glycocalyx injury and endothelial activation biomarkers within 48 hours of hospital admission. The primary outcome was the risk of mortality from all causes and the secondary outcomes were the risk of developing respiratory failure (RF) and multiple organ dysfunction syndrome (MODS) in patients with elevations of these biomarkers. MEASUREMENTS AND MAIN RESULTS: A total of 17 studies (3,529 patients) were included: 11 evaluated syndecan-1 (n=2,397) and 6 endocan (n=1,132). Syndecan-1 was higher in the group of patients who died than in those who survived [255 ng/mL (IQR: 139-305) vs. 83 ng/mL (IQR:40-111); p=0.014]. Patients with elevated syndecan-1 had a greater risk of death (OR 2.32; 95% CI 1.89, 3.10: p<0.001), MODS (OR 3.3; 95% CI 1.51, 7.25: p=0.003;), or RF (OR 7.53; 95% CI 1.86-30.45: p=0.005). Endocan was higher in patients who died [3.1 ng/mL (IQR 2.3, 3.7) vs. 1.62 ng/mL (IQR 1.2, 5.7); OR 9.53; 95% CI 3.34, 27.3; p<0.001], who had MODS (OR 8.33; 95% CI 2.07, 33.58; p=0.003) and who had RF (OR 9.66; 95% CI 2.26, 43.95; p=0.002). CONCLUSION: Patients with sepsis and abnormal glycocalyx injury and endothelial activation biomarkers have a greater risk of developing respiratory failure, multiple organ failure, and death. Microcirculatory impairment should be routinely evaluated in patients with sepsis, using biomarkers to stratify risk groups.

Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SARS-CoV-2 virus disease (COVID-19) is multisystem inflammatory syndrome (MIS-C). This new disease is characterized by a large inflammatory response and frequent cardiovascular, cutaneous and gastrointestinal disorders. We describe the first two cases of critically ill children with MIS-C who evidenced a large inflammatory response associated with elevated plasma and imaging biomarkers of endothelial activation and endothelial glycocalyx degradation. This microcirculation involvement in MIS-C could, at least partially, explain some of the clinical manifestations and laboratory and imaging alterations found in these patients. These findings contribute to a better understanding of this disease and suggest that medications to modulate the inflammatory response and protect or restore the endothelial glycocalyx should be considered in future studies.

Toma de decisiones centradas en la familia en la enfermedad renal crónica avanzada. De la autonomía individual a la autonomía familiar o comunitaria / Family Centered Decision Making in Advanced Chronic Kidney Disease. From individual autonomy to family or community autonomy / Tomada de decisões centradas na família na enfermidade renal crônica avançada. Da autonomia individual à autonomia familiar ou comunitária

Resumen El aumento de la tasa de incidencia y prevalencia de la enfermedad renal crónica plantea desafíos y dilemas éticos que tanto pacientes como familiares y profesionales de salud deben enfrentar diariamente. El objetivo de este artículo es reflexionar acerca de que, para la toma decisiones, los pacientes recurren a terceros como partícipes, lo que a nuestro juicio requiere un abordaje desde la autonomía solidaria. Se presenta el análisis de doce entrevistas semiestructuradas, realizadas a pacientes de 60 años o más, de distintos programas de la Unidad de Nefrología del Hospital Universitario San Ignacio, Colombia, entre 2017-2018. El artículo propone la necesidad de toma de decisiones centradas en la familia de los pacientes con enfermedades crónicas, antes de que su estado sea avanzado y los estados de inconciencia impidan su autodeterminación, considerando la determinación social de la autonomía.

Abstract The increase in the incidence and prevalence rate of Chronic Kidney Disease poses challenges and ethical dilemmas that patients, family members and health professionals must face daily. The objective of this article is to present a reflection on the way in which patients make recourse to third parties as participants in their decision-making, which would require an approach based on solidarity autonomy. The analysis of twelve semi-structured interviews conducted with patients 60 years of age and older, from different programs of the Nephrology Unit of the Hospital Universitario San Ignacio in the period 2017-2018 Colombia, is presented. This article proposes the need for family-centered decision making of patients with chronic diseases, before their state is advanced and states of unconsciousness prevent their self-determination, considering the social determination of autonomy.

Resumo O aumento da taxa de incidência e prevalência da enfermidade renal crônica coloca desafios e dilemas éticos que tanto pacientes como familiares e professionais da saúde devem enfrentar diariamente. O objetivo deste artigo é refletir acerca de que, para a tomada de decisões, os pacientes recorrem a terceiros como partícipes, o que a nosso juízo requer uma abordagem a partir da autonomia solidária. Se apresenta a análise de doze entrevistas semiestruturadas, realizadas com pacientes de 60 anos ou mais, de distintos programas da Unidade de Nefrologia do Hospital Universitário San Ignacio, Colômbia, entre 2017-2018. O artigo propõe a necessidade de tomada de decisões centradas na família dos pacientes com enfermidades crônicas, antes que seu estado esteja avançado e estados de inconsciência impeçam sua autodeterminação, considerando a determinação social da autonomia.

Muscle defects due to perturbed somite segmentation contribute to late adult scoliosis.

Scoliosis is an abnormal bending of the body axis. Truncated vertebrae or a debilitated ability to control the musculature in the back can cause this condition, but in most cases the causative reason for scoliosis is unknown (idiopathic). Using mutants for somite clock genes with mild defects in the vertebral column, we here show that early defects in somitogenesis are not overcome during development and have long lasting and profound consequences for muscle fiber organization, structure and whole muscle volume. These mutants present only mild alterations in the vertebral column, and muscle shortcomings are uncoupled from skeletal defects. None of the mutants presents an overt musculoskeletal phenotype at larval or early adult stages, presumably due to compensatory growth mechanisms. Scoliosis becomes only apparent during aging. We conclude that adult degenerative scoliosis is due to disturbed crosstalk between vertebrae and muscles during early development, resulting in subsequent adult muscle weakness and bending of the body axis.

Paediatric cardiomyopathies: echocardiographic diagnosis, clinical profile, and demographic characteristics: the experience of a tertiary referral centre for Latin American paediatric cardiology.

BACKGROUND: Although multiple studies have been conducted in the adult population, there is a vast knowledge gap regarding the epidemiologic characteristics of cardiomyopathies in the paediatric population. This issue is even more crucial when the precarious situation of medical research in Latin America is considered. Given the potential impact that these disorders could have on Latin American health systems, a comprehensive epidemiologic study regarding the clinical profile and sociodemographic characteristics of these patients will influence the way we approach paediatric cardiomyopathies. METHODS: An observational retrospective study was conducted at a tertiary referral centre for Colombian and Latin American paediatric cardiology. We analysed all cases of primary cardiomyopathies in children younger than 18 years of age who presented at our institution between 2010 and 2016. Cases of cardiomyopathies were classified according to World Health Organization guidelines. RESULTS: From a total of 29,533 children who attended our institution during the study period, 89 new cases of primary cardiomyopathies were identified. The median age at diagnosis was 11 years (interquartile range 4-9). Dilated cardiomyopathy accounted for 57.3% (n = 51) of cases; hypertrophic cardiomyopathy, 12.3% (n = 11); restrictive cardiomyopathy, 8.9% (n = 8); non-compacted cardiomyopathy, 7.8% (n = 7); arrhythmogenic ventricular cardiomyopathy, 6.7% (n = 6); and unspecified cardiomyopathy, 6.7% (n = 6). Heart failure was observed in 53.93% of the patients. The overall mortality was 12.36% (n = 11), which included two of eight patients who underwent cardiac transplantation.

Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock.

Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome. While the segmentation clock clearly operates in teleosts, the role of the sclerotome in establishing the axial skeleton is unclear. We severely disrupt zebrafish paraxial segmentation, yet observe a largely normal segmentation process of the chordacentra. We demonstrate that axial entpd5+ notochord sheath cells are responsible for chordacentrum mineralization, and serve as a marker for axial segmentation. While autonomous within the notochord sheath, entpd5 expression and centrum formation show some plasticity and can respond to myotome pattern. These observations reveal for the first time the dynamics of notochord segmentation in a teleost, and are consistent with an autonomous patterning mechanism that is influenced, but not determined by adjacent paraxial mesoderm. This behavior is not consistent with a clock-type mechanism in the notochord.

Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair.

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments.

Notochord Injury Assays that Stimulate Transcriptional Responses in Zebrafish Larvae.

Zebrafish have become an increasingly important model organism in the field of wound healing and regenerative medicine, due to their high regenerative capacity coupled with high-resolution imaging in living animals. In a recent study, we described multiple physical and chemical methods to induce notochord injury that led to highly specific transcriptional responses in notochord cellular subpopulations. The notochord is a critical embryonic structure that functions to shape and pattern the vertebrae and spinal column. Here, we describe precision needle injury, tail-notochord amputation, and chemical inhibition of caveolin that trigger a wound-specific wt1b expression response in the notochord sheath cell subpopulation. We propose that these procedures can be used to study distinct cell populations that make up the cellular processes of notochord repair.

Quantitative interaction mapping reveals an extended UBX domain in ASPL that disrupts functional p97 hexamers.

Interaction mapping is a powerful strategy to elucidate the biological function of protein assemblies and their regulators. Here, we report the generation of a quantitative interaction network, directly linking 14 human proteins to the AAA+ ATPase p97, an essential hexameric protein with multiple cellular functions. We show that the high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers. High-resolution structural and biochemical studies indicate that an extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers. This spontaneous process is accompanied by a reorientation of the D2 ATPase domain in p97 and a loss of its activity. Finally, we demonstrate that overproduction of ASPL disrupts p97 hexamer function in ERAD and that engineered eUBX polypeptides can induce cell death, providing a rationale for developing anti-cancer polypeptide inhibitors that may target p97 activity.

[Aquatic Ecological Index based on freshwater (ICE(RN-MAE)) for the Rio Negro watershed, Colombia]. / Indice de calidad ecológica con base en macroinvertebrados acuáticos para la cuenca del río negro (ICE(RN-MAE)), Colombia.

Aquatic Ecological Index based on freshwater (ICE(RN-MAE)) for the Rio Negro watershed, Colombia. Available indices to assess the ecological status of rivers in Colombia are mostly based on subjective hypotheses about macroinvertebrate tolerance to pollution, which have important limitations. Here we present the application of a method to establish an index of ecological quality for lotic systems in Colombia. The index, based on macroinvertebrate abundance and physicochemical variables, was developed as an alternative to the BMWP-Col index. The method consists on determining an environmental gradient from correlations between physicochemical variables and abundance. The scores obtained in each sampling point are used in a standardized correlation for a model of weighted averages (WA). In the WA model abundances are also weighted to estimate the optimum and tolerance values of each taxon; using this information we estimated the index of ecological quality based also on macroinvertebrate (ICE(RN-MAE)) abundance in each sampling site. Subsequently, we classified all sites using the index and concentrations of total phosphorus (TP) in a cluster analysis. Using TP and ICE(RN-MAE), mean, maximum, minimum and standard deviation, we defined threshold values corresponding to three categories of ecological status: good, fair and critical.

Índice de calidad ecológica con base en macroinvertebrados acuáticos para la cuenca del río Negro (ICE RN-MAE), Colombia

Aquatic Ecological Index based on freshwater (ICE RN-MAE) for the Río Negro watershed, Colombia. Available indices to assess the ecological status of rivers in Colombia are mostly based on subjective hypotheses about macroinvertebrate tolerance to pollution, which have important limitations. Here we present the application of a method to establish an index of ecological quality for lotic systems in Colombia. The index, based on macroinvertebrate abundance and physicochemical variables, was developed as an alternative to the BMWP-Col index. The method consists on determining an environmental gradient from correlations between physicochemical variables and abundance. The scores obtained in each sampling point are used in a standardized correlation for a model of weighted averages (WA). In the WA model abundances are also weighted to estimate the optimum and tolerance values of each taxon; using this information we estimated the index of ecological quality based also on macroinvertebrate (ICE RN-MAE) abundance in each sampling site. Subsequently, we classified all sites using the index and concentrations of total phosphorus (TP) in a cluster analysis. Using TP and ICE RN-MAE, mean, maximum, minimum and standard deviation, we defined threshold values corresponding to three categories of ecological status: good, fair and critical. Rev. Biol. Trop. 62 (Suppl. 2): 233-247. Epub 2014 April 01.

Los índices disponibles para la evaluación del estado ecológico de los ríos en Colombia están basados principalmente en hipótesis subjetivas generalizadas acerca de la toleración de los macroinvertebrados, un proceso que presenta limitaciones. En este estudio se presenta la aplicación de un método para establecer un índice de calidad ecológica para sistemas lóticos, basado en abundancia de macroinvertebrados y variables fisicoquímicas. Se tomó como caso de estudio la cuenca del rio Negro (Colombia). Este nuevo índice se ha formulado como alternativa al BMWP-Col y consiste en la determinación de un gradiente ambiental a partir de un Análisis de Correspondencia Canónica de correlaciones entre abundancias y registros fisicoquímicos. Los puntajes de las estaciones -obtenidos en las correlaciones- son estandarizados y usados en un modelo de Promedios Ponderados (WA); en el modelo se ponderan también las abundancias para estimar los valores óptimos y de tolerancia de cada taxón. Con ellos y la abundancia se calcula los valores del Índice de Calidad Ecológica con base en macroinvertebrados acuáticos para la cuenca del rio Negro (ICE RN-MAE). Se utilizan los valores del índice junto con las concentraciones de fósforo total (FT) en un análisis de agrupamiento, para así clasificar los sitios de estudio. De ahí se obtienen finalmente los valores medios, máximos, mínimos y de desviación estándar del ICE RN-MAE y FT. Con ellos se definen los umbrales que corresponden a diferentes categorías de calidad ecológica (buena, regular y crítica).

Análisis de mutaciones en los genes PINK1 Y PARKIN en pacientes colombianos con enfermedad de Parkinson / Analysis of mutations in the genes pink1 and parkin in Colombian patients with Parkinson's disease

La enfermedad de Parkinson es un desorden neurodegenerativo complejo, caracterizado por la pérdida progresiva de las neuronas dopaminérgicas de la sustancia nigra pars compacta. Factores tanto ambientales como genéticos se ha determinado que contribuyen a su desarrollo. Mutaciones en los genes PINK1 y PARKIN han sido asociadas con la enfermedad de inicio temprano e historia familiar. El objetivo del presente estudio fue identificar mutaciones en los genes PINK1 (exones 4 y 6) y PARKIN (exones 2 y 7) en 22 pacientes colombianos con EP de inicio temprano y/o antecedentes familiares, mediante amplificación por PCR y secuenciamiento. Las secuencias se compararon con la secuencia consenso de referencia. Se detectó una mutación homocigota de cambio en el marco de lectura ( frameshift) c.155 delA en el exón 2 del gen PARKIN en una paciente con inicio temprano de la enfermedad e historia familiar. Además se identificó la presencia de un polimorfismo en el intrón 2 del gen PARKIN en siete pacientes, uno de ellos en estado homocigoto. No se encontraron mutaciones en los exones 4 y 6 del gen PINK1. Se encontró una mutación homocigota c.155 delA en el exón 2 de PARKIN de una paciente con la enfermedad de Parkinson de inicio temprano con historia familiar. No se encontraron cambios el gen PINK1.

Parkinson's disease is a complex neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons of the substance nigra pars compacta. It has been determined that factors both environmental and genetic contribute to its development. Mutations in the genes PINK1 and PARKIN have been associated with the early onset of disease and family history. The goal of this study was to identify mutations in the PINK1 genes (exons 4 and 6) and PARKIN (exons 2 and 7) in 22 Colombian patients with EP of early onset and/or family history, by PCR amplification and sequencing. The sequences were compared with the reference consensus sequence. A homozygous change mutation was detected in the reading frame (frame shift) c.155 de la in exon 2 of the PAR-KIN gene in a patient with early onset of the disease and family history. In addition, the presence of a polymorphism in intron 2 of the PARKIN gene was identified in seven patients, one of them in homozygous state. Mutations were not found in exons 4 and 6 of the gene PINK1. A homozygous mutation c.155 de la in exon 2 of PARKIN was found in a female patient with Parkinson's disease early onset with family history. No changes to the gene PINK1 were found.

Manifestación atípica de encefalopatía posterior reversible (PRES) en Miastenia Gravis tratada con inmunoglobulina: reporte de caso / Atypical manifestation of posterior reversible encephalopathy (PRES) in Myasthenia Gravis treated with immunoglobulin: case report

El Síndrome de Encefalopatía Posterior Reversible (PRES por sus siglas en Inglés), es una entidad rara que se asocia a hipertensión arterial, enfermedades autoinmunes y medicamentos oncológicos. Se describe una paciente de 62 años, con crisis miasténica que posterior al tratamiento con inmunoglobulina G presentó deterioro y focalización neurológica, con lesiones en resonancia magnética inicial sugestivas de PRES, las cuales se confirmaron en control imaginológico. Esta entidad debe ser considerada en los pacientes que presenten deterioro neurológico focal posterior al uso de inmunoglobulina.

The Posterior Reversible Encephalopathy Syndrome (PRES), is a rare entity that is associated with hypertension, autoimmune diseases and cancer drugs. We describe a 62 year old female patient with myasthenic crisis that following treatment with immunoglobulin G who presents neurological impairment, with initial MRI lesions suggestive of PRES, which were confirmed in control imaging. This entity should be considered in patients presenting with focal neurological impairment following the use of immunoglobulin.

Neuropeptides: developmental signals in placode progenitor formation.

Few families of signaling factors have been implicated in the control of development. Here, we identify the neuropeptides nociceptin and somatostatin, a neurotransmitter and neuroendocrine hormone, as a class of developmental signals in both chick and zebrafish. We show that signals from the anterior mesendoderm are required for the formation of anterior placode progenitors, with one of the signals being somatostatin. Somatostatin controls ectodermal expression of nociceptin, and both peptides regulate Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, predating a complex nervous system.