Child Neurology: Common Occurrence of Narcolepsy Type 1 and Myasthenia Gravis.

Narcolepsy with cataplexy and myasthenia gravis are both chronic neurologic conditions causing symptoms of muscle weakness, often affecting facial muscles, and have both been attributed to an immune-mediated etiology. We report an adolescent girl diagnosed with both conditions and discuss possible shared mechanisms and the diagnostic challenges presented by her case to inform and aid clinicians managing children and young people with these rare conditions.

Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom.

Background: Real-world data on the efficacy and safety of onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) are needed, especially to overcome uncertainties around its use in older and heavier children. This study evaluated the efficacy and safety of OA in patients with SMA type 1 in the UK, including patients ≥2 years old and weighing ≥13.5 kg. Methods: This observational cohort study used data from patients with genetically confirmed SMA type 1 treated with OA between May 2021 and January 2023, at 6 infusion centres in the United Kingdom. Functional outcomes were assessed using age-appropriate functional scales. Safety analyses included review of liver function, platelet count, cardiac assessments, and steroid requirements. Findings: Ninety-nine patients (45 SMA therapy-naïve) were treated with OA (median age at infusion: 10 [range, 0.6-89] months; median weight: 7.86 [range, 3.2-20.2] kg; duration of follow-up: 3-22 months). After OA infusion, mean ± SD change in CHOP-INTEND score was 11.0 ± 10.3 with increased score in 66/78 patients (84.6%); patients aged <6 months had a 13.9 points higher gain in CHOP-INTEND score than patients ≥2 years (95% CI, 6.8-21.0; P < 0.001). Asymptomatic thrombocytopenia (71/99 patients; 71.7%), asymptomatic troponin-I elevation (30/89 patients; 33.7%) and transaminitis (87/99 patients; 87.9%) were reported. No thrombotic microangiopathy was observed. Median steroid treatment duration was 97 (range, 28-548) days with dose doubled in 35/99 patients (35.4%). There were 22.5-fold increased odds of having a transaminase peak >100 U/L (95% CI, 2.3-223.7; P = 0.008) and 21.2-fold increased odds of steroid doubling, as per treatment protocol (95% CI, 2.2-209.2; P = 0.009) in patients weighing ≥13.5 kg versus <8.5 kg. Weight at infusion was positively correlated with steroid treatment duration (r = 0.43; P < 0.001). Worsening transaminitis, despite doubling of oral prednisolone, led to treatment with intravenous methylprednisolone in 5 children. Steroid-sparing immunosuppressants were used in 5 children to enable steroid weaning. Two deaths apparently unrelated to OA were reported. Interpretation: OA led to functional improvements and was well tolerated with no persistent clinical complications, including in older and heavier patients. Funding: Novartis Innovative Therapies AG provided a grant for independent medical writing services.

Recurrent atraumatic compartment syndrome as a manifestation of genetic neuromuscular disease.

Compartment syndrome (CS) is a medical emergency that occurs secondary to excessively high pressures within a confined fibro-osseous space, resulting in reduced perfusion and subsequent tissue injury. CS can be divided into acute forms, most commonly due to trauma and considered an orthopaedic emergency, and chronic forms, most commonly presenting in athletes with recurrent exercise-induced pain. Downstream pathophysiological mechanisms are complex but do share commonalities with mechanisms implicated in genetic neuromuscular disorders. Here we present 3 patients with recurrent CS in the context of a RYR1-related disorder (n = 1) and PYGM-related McArdle disease (n = 2), two of whom presented many years before the diagnosis of an underlying neuromuscular disorder was suspected. We also summarize the literature on previously published cases with CS in the context of a genetically confirmed neuromuscular disorder and outline how the calcium signalling alterations in RYR1-related disorders and the metabolic abnormalities in McArdle disease may feed into CS-causative mechanisms. These findings expand the phenotypical spectrum of RYR1-related disorders and McArdle disease; whilst most forms of recurrent CS will be sporadic, above and other genetic backgrounds ought to be considered in particular in patients where other suggestive clinical features are present.

Early recognition of SGCE-myoclonus-dystonia in children.

AIM: To evaluate early dystonic features in children and adolescents with SGCE-myoclonus-dystonia. METHOD: In this cross-sectional study, 49 patients (26 females and 23 males) with SGCE-myoclonus-dystonia (aged 15y 2mo, SD 12y) with childhood-onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. RESULTS: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby-horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self-reported disability. INTERPRETATION: Children with SGCE-myoclonus-dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. WHAT THIS PAPER ADDS: Most children with SGCE-myoclonus-dystonia got writer's cramp and had walking and running dystonia. Writer's cramp was a key feature and should prompt SGCE genetic investigation. 'Circular shaking leg', 'dragging leg', and 'hobby-horse gait' were recognized as early gait patterns. Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms. Action dystonia rating scales are valid tools to assess severity in children.

ε-Sarcoglycan: Unraveling the Myoclonus-Dystonia Gene.

Myoclonus-dystonia (MD) is a rare childhood-onset movement disorder, with an estimated prevalence of about 2 per 1,000,.000 in Europe, characterized by myoclonic jerks in combination with focal or segmental dystonia. Pathogenic variants in the gene encoding ε-sarcoglycan (SGCE), a maternally imprinted gene, are the most frequent genetic cause of MD. To date, the exact role of ε-sarcoglycan and the pathogenic mechanisms that lead to MD are still unknown. However, there are more than 40 reported isoforms of human ε-sarcoglycan, pointing to a complex biology of this protein. Additionally, some of these are brain-specific isoforms, which may suggest an important role within the central nervous system. In the present review, we aim to provide an overview of the current state of knowledge of ε-sarcoglycan. We will focus on the genetic landscape of SGCE and the presence and plausible role of ε-sarcoglycan in the brain. Finally, we discuss the importance of the brain-specific isoforms and hypothesize that SGCE may play essential roles in normal synaptic functioning and their alteration will be strongly related to MD.

La técnica de perfilación criminológica: conocimiento, características y utilidad en Colombia / The Criminal Profiling Technique: Knowledge, Characteristics and Usefulness in Colombia / A técnica do perfil criminológico: conhecimento, característica e utilidade na Colômbia

Resumen La presente investigación tuvo como objetivo indagar sobre el conocimiento, las características y la utilidad de la técnica de perfilación criminológica dentro de una muestra de actores judiciales en Colombia, quienes, por sus funciones profesionales en la investigación criminal, se encontraban en posibilidad de aplicar la técnica. La metodología incluyó la realización de entrevistas semiestructuradas a 155 funcionarios pertenecientes a las principales instituciones de administración de justicia colombiana (Fiscalía, Policía Nacional, Defensoría del Pueblo, Instituto Nacional Penitenciario y Carcelario, y miembros de la rama judicial). Entre los resultados se encuentra que los actores judiciales consideran útil la técnica por la noción de cientificidad que tienen sobre ella. Asimismo, aunque se percibe útil, es poco usada debido al desconocimiento general derivado del poco entrenamiento recibido para su ejecución. Estos resultados se discuten frente a la historia reciente del estudio en materia criminológica en el país, la formación de sus profesionales y las brechas entre la investigación académica y su uso en la práctica de investigación criminal. Se concluye que la técnica en el contexto colombiano está aún en desarrollo, actualmente cuenta con algunas guías y protocolos al interior de cada institución y requiere de mayores ejercicios de evaluación de impacto y análisis exhaustivos de su relevancia y cientificidad.

Abstract This research study's objective was to explore the knowledge, characteristics and usefulness of the criminal profiling technique within a sample of judicial actors in Colombia who, due to their professional functions in criminal investigations, could possibly apply the technique. The methodology included performing semi-structured interviews on 155 officials belonging to Colombia's main institutions for the administration of justice (Prosecutor's Office, National Police, Ombudsman's Office, National Penitentiary and Prison Institute, and members of the judicial branch). Among the results, it was observed that judicial actors consider the technique useful due to the scientific notion they have regarding it. Furthermore, although it is perceived as being useful, it is seldom used because of a general lack of knowledge derived from scant training for its execution. These results are discussed in light of the recent criminological study carried out in the country, its professionals' education and the gaps in academic research and its use in criminal investigations. It was concluded that the technique is still being developed in the Colombian context. It currently have some guides and protocols within each institution, and requires more impact assessments and comprehensive analyses regarding its relevance and scientific nature.

Resumo O objetivo desta pesquisa foi indagar sobre o conhecimento, as características e a utilidade da técnica de perfil criminológico dentro de uma amostra de atores judiciais na Colômbia que, devido às suas funções profissionais na investigação criminal, são capazes de aplicar a técnica. A metodologia incluiu a realização de entrevistas semiestruturadas com 155 funcionários pertencentes às principais instituições de administração de justiça colombiana (Procuradoria, Polícia Nacional, Defensoria do povo, Instituto Nacional Penitenciário e Carcerário, e membros do poder judiciário). Entre os resultados, encontra-se que os atores judiciais consideram a técnica útil devido à noção de cientificidade que possuem sobre ela. Da mesma forma, embora seja percebida como útil, é pouco utilizada por causa do desconhecimento geral derivado do pouco treinamento recebido para sua execução. Esses resultados são discutidos à luz da história recente do estudo da criminologia no país, da formação de seus profissionais e as brechas entre a pesquisa acadêmica e sua utilização na prática da investigação criminal. Conclui-se que a técnica, no contexto colombiano, ainda está em desenvolvimento. Atualmente possui alguns guias e protocolos dentro de cada instituição e requer maiores exercícios de avaliação de impacto e análise exaustiva de sua relevância e cientificidade.

Delineating the motor phenotype of SGCE-myoclonus dystonia syndrome.

OBJECTIVE: To perform phenotype and genotype characterization in myoclonus-dystonia patients and to validate clinical rating tools. METHOD: Two movement disorders experts rated patients with the Burke-Fahn-Marsden and Unified-Myoclonus rating scales using a video-recording protocol. Clinimetric analysis was performed. SGCE mutations were screened by Sanger sequencing and multiplex ligation-dependent probe amplification. RESULTS: 48 patients were included and 43/48 rated. Mean age at assessment was 12.9±10.5 years (range 3-51) and 88% were ≤18 years of age. Myoclonus was a universal sign with a rostro-caudal severity-gradient. Myoclonus increased in severity and spread to lower limbs during action tests. Stimulus-evoked myoclonus was observed in 86.8% cases. Dystonia was common but mild. It had a focal distribution and was action-induced, causing writer's cramp (69%) and gait dystonia (34%). The severity of both myoclonus and dystonia had a strong impact on hand writing and walking difficulties. The Unified Myoclonus Rating scale showed the best clinimetric properties for the questionnaire, action myoclonus and functional subscales, and exceeded the Burke-Fahn-Marsden scale in its utility in assessing functional impairment in MDS patients. Twenty-one different SGCE mutations were identified in 45/48 patients, eleven being novel (most prevalent p. Val187*, founder mutation in Canary Islands). CONCLUSION: This study quantifies the severity of the motor phenotype in SGCE-myoclonus dystonia syndrome, with a special focus on children, and identifies disabilities in gross and fine motor tasks that are essential for childhood development. Our results contribute to the knowledge of SGCE-related MDS in the early stage of evolution, where disease-modifying therapies could be initiated in order to prevent long-term social and physical burdens.

Pancreatic ß-cell dysfunction in normoglycemic patients and risk factors.

AIMS: To evaluate pancreatic ß-cell function (ßf) in patients with normoglycemia (NG) and normal glucose tolerance (NGT) and related risk factors. METHODS: An observational and comparative study in 527 patients with NG and NGT that were divided by quartiles of ßf according to the disposition index derived from OGTT. Anthropometrical, clinical, nutritional, and biochemical variables were measured and associated with ßf. RESULTS: Quartiles of ßf were Q1 = DI < 1.93 n = 131, Q2 = DI 1.93-2.45 n = 134, Q3 = DI 2.46-3.1 n = 133, and Q4 = DI > 3.1 n = 129. There was a progressive reduction in pancreatic ß-cell function and it is negatively correlated with age, weight, BMI, total body fat and visceral fat, waist circumference, total cholesterol, LDL, and triglycerides (p < 0.01). Glucose levels during OGTT had a negative correlation with ßf; the product of fasting glucose by 1-h glucose had the best correlation with ßf (r = 0.611, p < 0.001) and was the best predictor of ßdf (AUC 0.816, CI 95% 0.774-0.857), even better than 1-h glucose (r = 0.581, p < 0.001). Energy, fat, and carbohydrate intake were negatively correlated with ßf (p < 0.05). Glucose levels at 1-h OGTT > 110 mg/dl were positively associated with pancreatic ßdf (OR 6.85, CI 95% 3.86-12.4). In the multivariate analysis, glucose levels during OGTT, fasting insulin, and BMI were the main factors associated with ßf. CONCLUSIONS: A subgroup of patients with NG and NGT may have a loss of 40% of their ßf. Factors related to this ßdf were age, adiposity, glucose during OGTT, and the product of fasting and 1-h glucose, as well as food intake.

Frameless robot-assisted pallidal deep brain stimulation surgery in pediatric patients with movement disorders: precision and short-term clinical results.

OBJECTIVE: The purpose of this study was to verify the safety and accuracy of the Neuromate stereotactic robot for use in deep brain stimulation (DBS) electrode implantation for the treatment of hyperkinetic movement disorders in childhood and describe the authors' initial clinical results. METHODS: A prospective evaluation of pediatric patients with dystonia and other hyperkinetic movement disorders was carried out during the 1st year after the start-up of a pediatric DBS unit in Barcelona. Electrodes were implanted bilaterally in the globus pallidus internus (GPi) using the Neuromate robot without the stereotactic frame. The authors calculated the distances between the electrodes and their respective planned trajectories, merging the postoperative CT with the preoperative plan using VoXim software. Clinical outcome was monitored using validated scales for dystonia and myoclonus preoperatively and at 1 month and 6 months postoperatively and by means of a quality-of-life questionnaire for children, administered before surgery and at 6 months' follow-up. We also recorded complications derived from the implantation technique, "hardware," and stimulation. RESULTS: Six patients aged 7 to 16 years and diagnosed with isolated dystonia ( DYT1 negative) (3 patients), choreo-dystonia related to PDE2A mutation (1 patient), or myoclonus-dystonia syndrome SGCE mutations (2 patients) were evaluated during a period of 6 to 19 months. The average accuracy in the placement of the electrodes was 1.24 mm at the target point. At the 6-month follow-up, patients showed an improvement in the motor (65%) and functional (48%) components of the Burke-Fahn-Marsden Dystonia Rating Scale. Patients with myoclonus and SGCE mutations also showed an improvement in action myoclonus (95%-100%) and in functional tests (50%-75%) according to the Unified Motor-Rating Scale. The Neuro-QOL score revealed inconsistent results, with improvement in motor function and social relationships but worsening in anxiety, cognitive function, and pain. The only surgical complication was medial displacement of the first electrode, which limited intensity of stimulation in the lower contacts, in one case. CONCLUSIONS: The Neuromate stereotactic robot is an accurate and safe tool for the placement of GPi electrodes in children with hyperkinetic movement disorders.

Nueva unidad de oncología infantil / New children's oncology unit

La humanización de los servicios de salud es la apuesta más importante que están desarrollando diferentes centros asistenciales en el país, lograr que el paciente y su familia se sientan más y mejor atendidos es todo un reto. Es así como el Hospital Infantil Universitario de San José cumpliendo con su promesa de valor "manos cálidas y confiables" renovó su unidad de oncología infantil convirtiéndola en un ambiente más agradable para los niños que atiende la institución. Este hospital era el antiguo Lorencita Villegas de Santos y fue rescatado en el año 2006 por la Fundación Universitaria de Ciencias de la Salud (FUCS) con 11 años de reapertura. Es conocido como el moderno Hospital Infantil Universitario de San José. La FUCS ha velado por su Institución y es así como gracias a su aporte económico y al de Asociados y Vélez, tras dos meses de remodelación, esta ala oncológica hoy es un hecho. Los niños tendrán un espacio más cómodo para ellos y sus acompañantes, en el que se sientan con un mejor estado de ánimo para afrontar sus procedimientos y recuperación. Es de resaltar que una quimioterapia puede tomar hasta seis u ocho horas diarias, lo cual genera un desgaste físico y mental que debe ser afrontado de la mejor manera.

Impact on Hip Fracture Mortality After the Establishment of an Orthogeriatric Care Program in a Colombian Hospital.

OBJECTIVE: The aim of this study is to evaluate mortality and survival rates of patients aged 65 years or older who sustained a hip fracture and were treated at a hospital in Bogotá, Colombia, after the establishment of an Orthogeriatric Program. METHOD: In total, 298 patients were treated according to the program's protocol. The primary outcome was 1-year mortality. Mortality predictors were estimated using Cox proportional hazards model, and survival was measured with Kaplan-Meier analysis. RESULTS: The annual survival rate increased from 80% to 89% ( p = .039) 4 years after its implementation. There was a significant decrease in mortality risk (Hazard Ratio = 0.54, p = .049). Arrhythmia, valvular heart disease, history of myocardial infarction, and age greater than 85 years were predictors of mortality. DISCUSSION: This is the first study in Latin America to show decreased mortality rates 1 year after the implementation of an Orthogeriatric Program. Our rates were lower than developed countries, suggesting the existence of additional factors that influence long-term outcomes.

Serotipificación molecular e identificación del fragmento 85M deaislamientos colombianos de Listeria monocytogenes: Un estudio descriptivo / Molecular serotyping and identification of the 85M gragment in different Colombian isolates of Listeria monocytogenes strains: A descriptive study

Introduction: Listeria monocytogenes is a pathogen acquired through the consumption of contaminated foods.Thirteen serotypes have been reported, of which 1/2a, 1/2b, and 4b are responsible for 98% of human listeriosis cases. This study examines the association between serotypes and virulent clones, offering greater information and providingtools to prevent and control diseases caused by L. monocytogenes serotype 4b. Objective: To identify the serotypes from L. monocytogene strains isolated from different samples by performingthe molecular subtyping technique; to determine the 85M fragment that codifies for epidemic clone I.Methods : 108 strains of L. monocytogenes were used, isolated from samples of animals, body fluids, foods, and food processing plant equipment and spaces. The samples were identified by following the Bacteriological AnalyticalManual protocol described by the Food and Drug Administration (FDA). The strains were identified by PolymeraseChain Reaction (PCR) using primers and a standardized protocol from a previous research project. Serotypeidentification was performed by multiplex PCR. The determination of the 85M fragment of the SSCS cassette was done by following the protocol by Yildrim et al. Results : Of the 108 L. monocytogenes strains analyzed, 60.2% (65 strains) belonged to the 4b-4d-4e serotype, 17.6%(19 strains) were identified as 1/2a-3a serotype, 14.8% (16 strains) were 4a-4c serotype, 3.7% (4 strains) belonged to the 1/2c-3c serotype, and (3.7%) corresponded to the 1/2b-3b-7 serotype. It was determined that the L. monocytogenes strains serotype 4b-4d-4e and 1/2a-3b have the 85M fragment of the SSCS cassette.Conclusion : This study reports the predominant existence of L. monocytogenes strains serotype 4b-4d-4e in food, environmental, and clinical samples. The presence of an epidemic clone I region was also found in L. monocytogenes strains.

Capacidad bactericida de Bifidobacterium sp. aislada de leche materna y de heces de neonatos, frente a los principales causantes de enfermedades transmitidas por alimentos / Antibiotic activity of Bifidobacterium sp. isolated from breast milk and newborn faeces, against the main causes for foodborne illnesses

Introducción. La microbiota del tubo digestivo humano contiene bacterias benéficas para la salud que regulan el funcionamiento del colon e inhiben algunos microorganismos patógenos intestinales. Las bifidobacterias aisladas de neonatos y de leche materna se usan como microorganismos probióticos para prevenir enfermedades infecciosas, incluidas las transmitidas por alimentos. Objetivo. Aislar e identificar Bifidobacterium sp. en humanos y determinar su capacidad bactericida frente a patógenos causantes de enfermedades transmitidas por alimentos, importantes en Colombia y en el mundo. Materiales y métodos. Se recolectaron 17 muestras de leche materna, y 19 muestras de meconio y heces de neonatos, en diferentes hospitales de Bogotá. Los 26 aislamientos sospechosos se identificaron a nivel de género mediante PCR 16-23S; para la identificación de especie, se secuenciaron algunos de los aislamientos. La capacidad antagonista de las 26 cepas de Bifidobacterium sp. fue evaluada contra Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Salmonella enteritidis ATCC 13076, Listeria monocytogenes ATCC 7644 y E. coli O157:H7 ATCC 35150. Para las cepas que presentaron mayor actividad antagonista, se analizó el extracto inhibidor con ensayos de difusión en placa. Resultados. Todas las cepas amplificaron la banda esperada para la confirmación de género; asimismo, las cepas Bif 013 y Bif 023 se identificaron por secuenciación como Bifidobacterium breve, con una homología del 97%. Del total de cepas, 17 mostraron capacidad de inhibir, al menos, uno de los patógenos evaluados. E. coli ATCC 25922 fue el patógeno más inhibido. Se determinó que la cepa Bif 023 es eficiente como antagonista, ya que inhibió todos los patógenos evaluados. Los halos de inhibición presentaron diámetros mayores a lo esperado, lo que indica una muy buena capacidad antagonista de las cepas nativas. Se aisló Bifidobacterium sp. de leche materna, meconio y heces de neonatos, por lo cual se confirmó que este microorganismo es microbiota humana (2). Conclusión. Se concluye que, debido a la gran capacidad antagonista de la mayoría de las bacterias aisladas, éstas pueden estar cumpliendo una importante función protectora en el recién nacido, en particular las cepas Bif 013 y Bif 023 aisladas de materia fecal. Estos microorganismos deben continuar siendo estudiados para definir su potencial probiótico. También, se pueden evaluar para bioconservación en la industria y contra patógenos transmitidos por alimentos.

Introduction. The microbiota in the human gastrointestinal tract contains beneficial microorganisms for human health, which contribute to the regulation of colonic function and inhibition of some intestinal pathogens growth. Bifidobacterium sp. isolated from newborns and breast milk are used as probiotic microorganisms, which are useful in the prevention of infectious diseases including foodborne illnesses. Objective: To isolate and identify human Bifidobacterium sp. and to determine its antibiotic activity against important pathogens which cause foodborne illnesses in Colombia and the world. Materials and methods. 17 breast milk samples and 19 meconium and newborn faeces samples were collected from different hospitals in Bogotá. 26 presumptive Bifidobacterium strains were identified at genus level by PCR 16-23S; some strains were identified at species level by nucleic acid sequencing. The antagonistic activity of 26 Bifidobacterium sp. strains was tested against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Salmonella enteritidis ATCC 13076, Listeria monocytogenes ATCC 7644 and E. coli O157:H7 ATCC 35150. For the strains that showed a greater antibiotic activity, the inhibitory compound was analyzed using disk diffusion tests. Results. All strains amplified the expected band for genus confirmation. Strains Bif 023 and Bif 013 were identified by DNA-sequencing as Bifidobacterium breve, with 97% homology. 17 strains were able to inhibit at least one of the pathogens tested. Escherichia coli ATCC 25922 was the most inhibited. It was determined that the strain Bif 023 is highly efficient as an antagonist strain due its ability to inhibit all the evaluated pathogens. Inhibition areas showed higher diameters than expected, suggesting an enhanced antagonist capacity of native strains. Bifidobacterium sp. was isolated from breast milk, meconium and newborn faeces which confirmed that this microorganism is human microbiota. Conclusion. Due to the high antagonist activity of most isolated bacteria, they could be playing an important protective function in the newborn, in particular strains Bif 013 and Bif 023, isolated from faeces. Other studies must be performed with these organisms to determine their probiotic potential as well as their use in the biocontrol industry due their activity against foodborne pathogens.

Molecular characterization of diarrheagenic Escherichia coli strains from stools samples and food products in Colombia.

The prevalence of diarrheagenic Escherichia coli in childhood diarrhea and the role of contaminated food products in disease transmission in Colombia are largely unknown. The aim of this study is to identify E. coli pathotypes, including E. coli O157:H7, from 108 stool samples from children with acute diarrhea, 38 meat samples and 38 vegetable samples. Multiplex PCR and Bax Dupont systems were used for E. coli pathotype detection. Eighteen (9.8%) E. coli diarrheagenic pathotypes were detected among all clinical and food product samples tested. Four different pathotypes were identified from clinical samples, including enteroaggregative E. coli, enterotoxigenic E. coli, shiga-toxin producing E. coli, and enteropathogenic E. coli. Food product samples were positive for enteroaggregative and shiga-toxin producing E. coli, suggesting that meat and vegetables may be involved in transmission of these E. coli pathotypes in the community. Most E. coli strains identified belong to the phylogenetic groups A and B1, known to be associated with intestinal rather than extraintestinal E. coli clones. Our data is the first molecular E. coli report that confirms the presence of E. coli pathotypes circulating in Colombia among children with diarrhea and food products for human consumption. Implementation of multiplex PCR technology in Latin America and other countries with limited resources may provide an important epidemiological tool for the surveillance of E. coli pathotypes from clinical isolates as well as from water and food product samples.

Aislamiento e identificación de Enterobacter sakazakii en lactarios de Bogotá / Isolation and identification of Enterobacter sakazakii in milk feeders of Bogotá, D. C

Introducción. Enterobacter sakazakii es un patógeno oportunista emergente de alto riesgo, responsable de meningitis grave y enterocolitis necrosante. El principal vehículo de transmisión de esta bacteria son los productos infantiles deshidratados, debido a su contaminación después del tratamiento térmico. Objetivo. Identificar cepas de E. sakazakii en muestras de lactarios recolectadas en la ciudad de Bogotá, D.C. Materiales y métodos. Se analizaron 222 muestras de 9 lactarios, de superficies estériles y no estériles, utensilios empleados para la preparación de biberones y operarios. Se realizó recuento de coliformes totales y detección de E. sakazakii utilizando el protocolo propuesto por la Food and Drug Administration y por el Sistema Automático Bax® Dupont Qualicon. Resultados. De las 222 muestras recolectadas en las clínicas de Bogotá, se reportó que 27,4% (61) de las muestras analizadas presentaban coliformes totales; se detectó la presencia de E. sakazakii en 3,6% por el método automatizado de PCR BAX Dupont a partir de muestras de biberones y superficies. Conclusiones. Se demostró la presencia de E. sakazakii en lactarios en Colombia. Debido a que este microorganismo es un patógeno oportunista de alto riesgo para neonatos y que está asociado a las prácticas higiénicas en los lactarios, la información de este estudio puede ser útil para la toma de medidas profilácticas que reduzcan el riesgo de contaminación con este patógeno para la población infantil y, también, aporta información importante para la salud pública.

Introduction: Enterobacter sakazakii is an emergent opportunistic pathogen of high risk responsible of severe meningitis and necrotizing enterocolitis in neonates and infants with underlying medical conditions. One of the principal transmission vehicles for the transmission of these bacteria, is the infant dehydrated formula after exposing them to the heating treatment. Objective: To identify strains of E. sakazakii in milk feeders’ samples from Bogotá. Materials and methods: 222 samples from 9 milk feeders including sterile and non sterile surfaces, utensils used for the formula preparation and food handlers were analyzed. Total coliforms counts and identification of E. sakazakii was done using the FDA protocol and the automatic system Bax ® Dupont Qualicon. Results: From de 222 samples collected from hospitals in Bogotá, it was reported that 27.4% (61) had total coliforms, and the presence of E. sakazakii was detected in 3.6% (8) from one feeding bottle and surfaces. Conclusion: The presence of E. sakazakii strains was reported in Colombian milk feeders. Because this microorganism is a high risk opportunistic pathogen for newborn infants, usually associated with hygiene practices in milk feeders, the information of this research could be useful to develop preventive measurements to reduce the risk of contamination in the infant population and provides important public health information.

Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism.

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.

Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism / Desfecho Fatal de uma Paciente com Carcinoma Papilífero de Tiróide e Doença de Graves: possível Implicação do Mecanismo de Sinalização Cruzada

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8 percent (n.v. < 10 percent). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.

Paciente de 29 anos foi encaminhada ao Hospital de Clínicas por causa de convulsões generalizadas. Apresentava hipertiroidismo tratado com metimazol (MMI). A ressonância magnética mostrava quatro lesões metastáticas cerebrais. Possuía bócio com nódulo frio e linfonodo palpável ipsilateral. Usando 5 mg de MMI, a paciente apresentava hipertiroidismo subclínico e TRAb = 47,8 por cento (normal < 10 por cento). A tomografia computadorizada também mostrava metástases pulmonares. A paciente foi submetida a tiroidectomia total com dissecção cervical modificada e recebeu dose acumulada de radioiodo de 700 mCi durante o período de dois anos. Foi analisado o DNA extraído de tecido emblocado em parafina do tumor, do linfonodo metastático e de tecido tiroidiano não-tumoral. Foram encontradas mutações pontuais em dois genes: uma substituição do genótipo selvagem CAA no códon 61 de /N-RAS/ por CAT, substituindo a glicina pela histidina (G61H) e uma substituição da seqüência normal GCC no códon 623 do gene TSHR por TCC, trocando a alanina pela serina (A623S). Não foram encontradas mutações no tecido não-tumoral. Estudos in vitro mostraram ativação constitutiva de TSHR. Já que esta mutação ativadora de TSHR foi incapaz de atingir o final da cascata PKA no tecido tumoral, sugere-se que um mecanismo de cross-signaling possa explicar o desvio da cascata do receptor de TSH para outra mais proliferativa, envolvendo MAPKinase e levando ao comportamento mais agressivo deste câncer papilífero.

Characterization of Shiga toxigenic Escherichia coli isolated from foods.

The aim of this study was to characterize Shiga toxigenic Escherichia coli (STEC) by PCR using strains isolated from ham, beef, and cattle in Colombia. A total of 189 E. coli strains were tested for the presence of the uidA, stx1, and stx2 genes, and identification was confirmed by the automated PCR BAX system for E. coli O157:H7. Genes encoding Shiga-like toxins (stx) were found in eight (6.06%) of 132 strains previously isolated from minced beef; four (50%) of these strains yielded amplification products for both toxin genes (stx1 and stx2), and four (50%) yielded products only for the stx2 toxin. None of the strains analyzed were positive by PCR for the presence of the single base-pair mutation in the uidA gene from E. coli O157:H7; these results were confirmed by the BAX system analysis. A multiplex PCR assay was standardized for the three genes. Results from this study confirmed previous data about the low prevalence of E. coli O157:H7 and Shiga-like toxins in Colombia and is the first known report of the prevalence of non-O157 enterohemorrhagic E. coli in this country.

[Molecular typing of Listeria monocytogenes isolated from clinical and food samples]. / Tipificación molecular de Listeria monocytogenes aisladas de muestras clínicas y alimentos.

INTRODUCTION: Listeria monocytogenes is an emergent foodborne pathogen acquired by the ingestion of contaminated food. This bacterium causes a disease called listeriosis, whose mortality rate world wide is around 20% to 30%, reaching up to 80% in cases of neonatal infections. The random amplified polymorphic DNA technique allows different isolates to be distinguished and characterized at the molecular level, which can provide useful information about the diversity of this pathogen in Colombia. OBJECTIVE: To molecularly characterize different L. monocytogenes isolates from food and clinical samples using this technique to determine possible relationships among these two origins. MATERIALS AND METHODS: Thirty eight L. monocytogenes isolates were analyzed; 22 from human clinical samples and 16 from food processing plants and food using two 10bp primers (HLW74, Arbitrary). The data were analyzed using Quantity One and SYN-TAX software. RESULTS: A high percentage of polymorphism was detected with both primers (HLWL-74, 81.81%; Arbitrary, 85.71%). Two major lineages were found, which were divided into four major clusters (A, B C and D) and great genetic diversity was observed. Most of the clinical isolates were grouped within the same cluster, and were more distantly related to the food isolates. CONCLUSION: The results of this study demonstrate a high degree of genetic diversity of DNA polymorphisms among the L. monocytogenes isolates circulating in Colombia, which could reflect phenotypic and pathogenic differences in these isolates.