Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Low-cost air, noise, and light pollution measuring station with wireless communication and tinyML.

Different types of environmental pollution cause negative consequences to ecosystems throughout the globe, which humanity is now trying to mitigate. It is necessary to know the level of pollution problems in the immediate environment, to evaluate the impact of human activities, and mitigation strategies necessary to ensure habitability. For this reason, in this work, a low-cost pollution measurement station for outdoor or indoor use is proposed and developed that measures air pollution (particulate matter and CO2), noise (level and direction), light pollution (power and multispectral), and also relative humidity and ambient temperature. The system stores the data in an SD memory or transmits data in real-time to the internet via WiFi. The purposes of the system are to be used in environmental studies, to deploy monitoring networks, or to ensure the habitability of a living or working space. The prototype integrates the measurement of the different sources of contamination in a single compact device at USD$ 628.12 without sacrificing measurement accuracy. The system is validated for each variable with reference equipment, obtaining an average error of approximately 2.67% in the measurement of all the variables measured. The system is easy to assemble and has an option for power supply using solar photovoltaic devices and an alternative for connection to 2G/3G mobile networks.

Epidemiology of Non-Tuberculous Mycobacteria isolated from clinical specimens in Madrid, Spain, from 2013 to 2017.

The epidemiology of non-tuberculous mycobacteria (NTM) in Spain is largely unknown because systematic reporting is not compulsory. The aim of our study was to describe the frequency and diversity of NTM species in our region and their distribution according to the source sample, gender, and age of the patients. We performed a multicenter study of all NTM isolated in 24 public hospitals in Madrid from 2013 to 2017. A total of 6.923 mycobacteria were isolated: 4535 (65.5%) NTM, and 2.388 (34.5%) Mycobacterium tuberculosis complex (MTB). Overall, 61 different NTM species were identified. The most frequently isolated species were Mycobacterium avium complex (47.7%), M. lentiflavum (12.2%), M. gordonae (9.2%), M. fortuitum (8.9%), and M. abscessus (3.9%). Whereas MTB cases were stable during the study period, the number of NTM isolates increased considerably from 930 isolates in 2013 to 1012 in 2017; a sharp increase occurred in the last year. The rise in NTM isolates was mostly due to M. lentiflavum, M. kansasii, and M. abscessus mainly isolated from respiratory specimens in patients older than 60. The increase in isolation rate of NTM in our region is consistent with the increasing rates reported worldwide in the last decades. The rise in NTM isolates was mainly attributed to M. lentiflavum but it also should be noted the increasing of species with high pathogenic potential such as M. kansasii and M. abscessus.

[Pregnancy during chronic hemodialysis. A series of cases]. / Embarazo en hemodiálisis crónica: experiencia de un hospital universitario.

BACKGROUND: Pregnancies in women with end stage renal failure are uncommon. However, correction of anemia and improvement in dialysis techniques increases the rate of successful pregnancies. AIM: To describe a 16 years' experience treating pregnant women on hemodialysis and to analyze maternal-fetal outcomes. MATERIALS AND METHODS: Observational study of a dialysis center historical cohort in a university hospital, between 2001 and 2016. RESULTS: Thirteen pregnancies were found in 11 women aged 23 to 32 years, 77% on dialysis prior to pregnancy. Residual diuresis was 1,300 [625-1,575] mL in 24 hrs. The baseline hemoglobin was 9.0 [7.6-9.9] g/dL and 92% of patients did not use contraception. The pre-dialysis blood urea nitrogen was 34 [29-36] mg /dL. An ultrasound to confirm pregnancy was done in all. At 23 [14-25] weeks of pregnancy, dialysis hours were increased, reaching 24 [19.5-24.0] hours per week. The most common complications were severe arterial hypertension (54%), severe anemia (46%), polyhydramnios (31%) and severe intrauterine growth retardation (IUGR) (23%). The median time of pregnancy at delivery was 34 [29-34] weeks. Neonatal median hospitalization length was 4 [4-32] days, with 18% of neonatal deaths. CONCLUSIONS: Pregnancies in dialysis are no longer exceptional. Despite better maternal and fetal outcomes, morbidity and mortality remains higher than in the normal population, which makes multidisciplinary management essential.

Embarazo en hemodiálisis crónica: experiencia de un hospital universitario / Pregnancy during chronic hemodialysis. A series of cases

Background: Pregnancies in women with end stage renal failure are uncommon. However, correction of anemia and improvement in dialysis techniques increases the rate of successful pregnancies. Aim: To describe a 16 years' experience treating pregnant women on hemodialysis and to analyze maternal-fetal outcomes. Materials and Methods: Observational study of a dialysis center historical cohort in a university hospital, between 2001 and 2016. Results: Thirteen pregnancies were found in 11 women aged 23 to 32 years, 77% on dialysis prior to pregnancy. Residual diuresis was 1,300 [625-1,575] mL in 24 hrs. The baseline hemoglobin was 9.0 [7.6-9.9] g/dL and 92% of patients did not use contraception. The pre-dialysis blood urea nitrogen was 34 [29-36] mg /dL. An ultrasound to confirm pregnancy was done in all. At 23 [14-25] weeks of pregnancy, dialysis hours were increased, reaching 24 [19.5-24.0] hours per week. The most common complications were severe arterial hypertension (54%), severe anemia (46%), polyhydramnios (31%) and severe intrauterine growth retardation (IUGR) (23%). The median time of pregnancy at delivery was 34 [29-34] weeks. Neonatal median hospitalization length was 4 [4-32] days, with 18% of neonatal deaths. Conclusions: Pregnancies in dialysis are no longer exceptional. Despite better maternal and fetal outcomes, morbidity and mortality remains higher than in the normal population, which makes multidisciplinary management essential.

"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression.

Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female puberty via epigenetic repression of the puberty-activating gene, Kiss1. SIRT1 is expressed in hypothalamic Kiss1 neurons and suppresses Kiss1 expression. SIRT1 interacts with the Polycomb silencing complex to decrease Kiss1 promoter activity. As puberty approaches, SIRT1 is evicted from the Kiss1 promoter facilitating a repressive-to-permissive switch in chromatin landscape. Early-onset overnutrition accelerates these changes, enhances Kiss1 expression and advances puberty. In contrast, undernutrition raises SIRT1 levels, protracts Kiss1 repression and delays puberty. This delay is mimicked by central pharmacological activation of SIRT1 or SIRT1 overexpression, achieved via transgenesis or virogenetic targeting to the ARC. Our results identify SIRT1-mediated inhibition of Kiss1 as key epigenetic mechanism by which nutritional cues and obesity influence mammalian puberty.

Hypothalamic epigenetics driving female puberty.

Puberty involves a series of morphological, physiological and behavioural changes during the last part of the juvenile period that culminates in the attainment of fertility. The activation of the pituitary-gonadal axis by increased hypothalamic secretion of gonadotrophin-releasing hormone (GnRH) is an essential step in the process. The current hypothesis postulates that a loss of transsynaptic inhibition and a rise in excitatory inputs are responsible for the activation of GnRH release. Similarly, a shift in the balance in the expression of puberty activating and puberty inhibitory genes exists during the pubertal transition. In addition, recent evidence suggests that the epigenetic machinery controls this genetic balance, giving rise to the tantalising possibility that epigenetics serves as a relay of environmental signals known for many years to modulate pubertal development. Here, we review the contribution of epigenetics as a regulatory mechanism in the hypothalamic control of female puberty.

Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

Valor de la ecografía ganglionar previa a la biopsia del ganglio centinela en 384 pacientes con melanoma: análisis de coste-efectividad / Use of Lymph Node Ultrasound Prior to Sentinel Lymph Node Biopsy in 384 Patients with Melanoma: A Cost-Effectiveness Analysis

INTRODUCCIÓN Y OBJETIVOS: La ecografía ganglionar locorregional como parte de la estadificación previa a la biopsia del ganglio centinela (BSGC) en pacientes con melanoma no se incluye habitualmente en las guías de manejo. El objetivo de este estudio es evaluarla desde la perspectiva clínica y económica. PACIENTES Y MÉTODOS: Estudio retrospectivo de 384 pacientes con melanoma primario de estadios clínicos I-II, en el periodo 2004-2015, a los que se les realizó una ecografía ganglionar locorregional (±biopsia ecodirigida) previa a la BSGC. Se evaluó la fiabilidad de la técnica y se realizó un análisis de su coste efectividad. RESULTADOS: En 23 pacientes (6%) se pudo evitar la realización de la BSGC mediante la técnica. La ecografía mostró una sensibilidad del 46% y una especificidad del 76% para la detección de ganglios metastásicos clínicamente no palpables. Los falsos negativos fueron significativamente más frecuentes en pacientes mayores de 60 años y con tumores <2mm. El coste unitario del proceso de estadificación mediante BSGC con ecografía-biopsia ecodirigida generó un sobrecoste de 16,30 €. El análisis coste-efectividad identificó como estrategia dominante desde ese punto de vista el protocolo de estadificación con ecografía y BSGC, con una ratio coste-efectividad inferior a la de la alternativa consistente en BSGC (8.095,24 vs. 28.605,00 € CONCLUSIONES: La ecografía con biopsia ecodirigida como método diagnóstico de estadificación previo a la BSGC es una herramienta útil y coste-efectiva, que no sustituye a la BSGC, pero que permite en un porcentaje no desdeñable de casos evitar su realización

BACKGROUND AND OBJECTIVES: Locoregional lymph node ultrasound is not typically included in guidelines as part of the staging process prior to sentinel lymph node biopsy (SLNB). The objective of the present study was to make a clinical and economic analysis of lymph node ultrasound prior to SLNB. MATERIALS AND METHODS: We performed a retrospective study of 384 patients with clinical stage I-II primary melanoma who underwent locorregional lymph node ultrasound (with or without ultrasound-guided biopsy) prior to SLNB between 2004 and 2015. We evaluated the reliability and cost-effectiveness of the strategy. RESULTS: Use of locorregional lymph node ultrasound avoided SLNB in 23 patients (6%). Ultrasound had a sensitivity of 46% and specificity of 76% for the detection of metastatic lymph nodes that were not clinically palpable. False negatives were significantly more common in patients aged over 60 years and in tumors with a thickness of less than 2mm. The staging process using SLNB and ultrasound with ultrasound-guided biopsy produced an increase of €16.30 in the unit price. Our cost-effectiveness analysis identified the staging protocol with ultrasound and SLNB as the dominant strategy, with a lower cost-effectiveness ratio than the alternative, consisting of SLNB alone (8,095.24 vs. € 28,605.00). CONCLUSIONS: Ultrasound with ultrasound-guided biopsy for the diagnostic staging of melanoma prior to SLNB is a useful and cost-effective tool. This procedure does not substitute SLNB, though it does allow to avoid SLNB in a not insignificant proportion of patients

Use of Lymph Node Ultrasound Prior to Sentinel Lymph Node Biopsy in 384 Patients with Melanoma: A Cost-Effectiveness Analysis. / Valor de la ecografía ganglionar previa a la biopsia del ganglio centinela en 384 pacientes con melanoma: análisis de coste-efectividad.

BACKGROUND AND OBJECTIVES: Locoregional lymph node ultrasound is not typically included in guidelines as part of the staging process prior to sentinel lymph node biopsy (SLNB). The objective of the present study was to make a clinical and economic analysis of lymph node ultrasound prior to SLNB. MATERIALS AND METHODS: We performed a retrospective study of 384 patients with clinical stage I-II primary melanoma who underwent locorregional lymph node ultrasound (with or without ultrasound-guided biopsy) prior to SLNB between 2004 and 2015. We evaluated the reliability and cost-effectiveness of the strategy. RESULTS: Use of locorregional lymph node ultrasound avoided SLNB in 23 patients (6%). Ultrasound had a sensitivity of 46% and specificity of 76% for the detection of metastatic lymph nodes that were not clinically palpable. False negatives were significantly more common in patients aged over 60 years and in tumors with a thickness of less than 2mm. The staging process using SLNB and ultrasound with ultrasound-guided biopsy produced an increase of €16.30 in the unit price. Our cost-effectiveness analysis identified the staging protocol with ultrasound and SLNB as the dominant strategy, with a lower cost-effectiveness ratio than the alternative, consisting of SLNB alone (8,095.24 vs. €28,605.00). CONCLUSIONS: Ultrasound with ultrasound-guided biopsy for the diagnostic staging of melanoma prior to SLNB is a useful and cost-effective tool. This procedure does not substitute SLNB, though it does allow to avoid SLNB in a not insignificant proportion of patients.

DISEÑO DE UNA PLATAFORMA INTEROPERABLE PARA UN OBSERVATORIO DE HÁBITOS Y ESTILOS DE VIDA SALUDABLE / DESIGN OF A INTEROPERABLE OBSERVATORY PLATFORM FOR HABITS ANDHEALTHY LIFESTYLES / CONCEPÇÃO DE UMA PLATAFORMA INTEROPERÁVEL PARA UM OBSERVATÓRIO HÁBITOS E ESTILOS DE VIDA SAUDÁVEIS

Esta investigación muestra el diseño de una plataforma interoperable que hace uso del estándar HL7 (Health Level Seven) y permite el registro y análisis de datos relacionados con estilos de vida saludable y prácticas de actividad física en adultos y adultos mayores de las zonas rurales de Colombia. El proyecto se centra en la utilización de las TIC para generar un sistema interoperable que permita la consolidación de los datos, con el fin de facilitar cifras epidemiológicas, hacer diagnósticos que permitan generar estrategias de promoción de la salud y prevención de la enfermedad en las que se promueva la actividad física; y consolidar un marco de referencia para las entidades interesadas. Esta plataforma provee un servicio de integración que puede ser utilizado por entidades externas, compartiendo así información relacionada con hábitos y estilos de vida saludables. Dicha plataforma, utiliza tecnología web ASP.net, con un modelo arquitectural MVC (Modelo Vista Controlador), lenguaje C#, un motor de base de datos SQLServer y servicios web a nivel de integración que usa HL7 como estándar de intercambio de mensajes. Se generó una prueba de control realizada en el año 2014, en ocho municipios del departamento de Cundinamarca en los cuales se aplicaron 304 instrumentos, con los cuales se alimentó la plataforma.

This research shows the design of an interoperable platform that uses the HL7 standard (Health Level Seven) and allows the record and analysis of data related to healthy lifestyles and practices of physical activity in adults and older adults in rural areas of Colombia. The project focuses on the use of ICT to generate an interoperable system that allows the consolidation of data, in order to facilitate epidemiological records, make diagnoses that generate strategies for health promotion and disease prevention in which promote physical activity; and build a framework for stakeholders. This platform provides an integration service that can be used by external entities, to reporting information related to habits and healthy lifestyles. This platform uses web ASP.net technology with architectural model MVC (Model View Controller), C # language, a database SQLServer motor and web services to integration with HL7 standard for the exchange of information. Was performed a control test in to 2014, in eight municipalities of the department of Cundinamarca in which 304 instruments were applied to upload to the platform.

Esta pesquisa mostra o desenho de uma plataforma interoperável que usa o HL7 (Health Level Seven) padrão e permite a gravação e análise de dados relacionados com os estilos de vida saudáveis e prática de atividade física em adultos e idosos nas zonas rurais da Colômbia. O projecto centra-se na utilização das TIC para gerar um sistema de interoperabilidade que permite a consolidação de dados, a fim de facilitar números epidemiológicos, fazer diagnósticos que podem gerar estratégias para promover a saúde e prevenção de doença em que promoção da atividade física; e construir uma estrutura para as partes interessadas. Esta plataforma fornece um serviço de integração que pode ser usado por entidades externas, a partilha de informações relacionadas a hábitos e estilos de vida saudáveis. Esta plataforma, utilizando a tecnologia web ASP.net com um padrão de arquitetura MVC (Model View Controller), a linguagem C#, banco de dados SQLServer do motor e nível de integração de serviços web usando a troca de mensagens HL7 padrão. Um teste de controle realizado em 2014, em oito municípios de Cundinamarca em que foram aplicados 304 instrumentos, com os quais a plataforma foi alimentado foi gerado.

Fiebre recurrente transmitida por garrapatas en área rural del sur de España / Tick-borne relapsing fever in a rural area of southern Spain

INTRODUCCIÓN: La fiebre recurrente transmitida por garrapatas (FRTG) es una enfermedad zoonótica producida por espiroquetas del género Borrelia. Es una enfermedad infradiagnosticada en nuestro medio debido al bajo índice de sospecha y a la dificultad en su diagnóstico. El objetivo del estudio es presentar nuestra experiencia en el manejo diagnóstico y terapéutico de la FRTG y revisar la literatura. MÉTODOS: Análisis retrospectivo de pacientes con FRTG ingresados en nuestro centro durante el periodo 2002-2012. Se analizan variables epidemiológicas, clínicas, microbiológicas, tratamiento y resultado. RESULTADO: Se identificaron 9 pacientes con FRTG. La mediana de edad fue de 11 años. Todos los casos ocurrieron durante meses cálidos. La clínica de presentación fue de episodios recurrentes de fiebre con escalofríos, cefalea, vómitos, mialgias y dolor abdominal. Se identificó afectación meníngea en 2 casos. En 2 pacientes existía infección por Borrelia en otros miembros de la familia en el momento del diagnóstico. La media de PCR fue de 187 mg/l y el 56% de casos presentaron trombocitopenia. Se visualizó Borrelia spp. en frotis de sangre periférica en el 67%. Todos los pacientes recibieron tratamiento antibiótico. Se empleó doxiciclina en mayores de 8 años y eritromicina y penicilina en menores de esta edad. Se produjo reacción de Jarisch- Herxheiner en un paciente. La evolución fue satisfactoria en todos los casos, sin secuelas. CONCLUSIONES: Subrayamos la importancia de mantener un elevado índice de sospecha de FRTG en regiones endémicas. El diagnóstico precoz, junto con el correcto tratamiento, permite evitar la aparición de recurrencias febriles y potenciales complicaciones

INTRODUCTION: Tick-borne relapsing fever (TBRF) is a zoonotic disease caused by spirochetes of the genus Borrelia. This disease is underdiagnosed in our area due to a low index of suspicion among clinicians, as well as its difficult diagnosis. This study aims to present our experience in the diagnosis and therapeutic management of TBRF and a literature review. METHODS: A retrospective medical chart review was carried out on children diagnosed of TBRF from 2002 to 2012 in our hospital, and included clinical, epidemiological, microbiological, treatment, and outcome data. RESULTS: Nine children with TBRF were identified. Median age was 11 years. All cases occurred during warm months. The most frequent presenting clinical findings were fever, chills, headache, vomiting, myalgia and abdominal pain. Meningeal involvement was identified in 2 cases. In the case of 2 patients, Borrelia infection was identified in several relatives at the time of diagnosis. Mean C-protein reactive was 187 mg/L, and low platelet counts were observed in 56% of the cases. Borrelia spp. was visualized in peripheral blood smears in 67% of cases. All of the patients received antibiotic treatment. Doxycycline was used in children older than 8 years and erythromycin and penicillin in the younger ones. Jarisch-Herxheiner reaction occurred in one patient. All cases resolved without sequelae. CONCLUSIONS: We emphasize the importance of maintaining a high level of suspicion in endemic regions of TBRF. Early diagnosis and a correct therapy can prevent the appearance of subsequent fever recurrences and potential complications

[Tick-borne relapsing fever in a rural area of southern Spain]. / Fiebre recurrente transmitida por garrapatas en área rural del sur de España.

INTRODUCTION: Tick-borne relapsing fever (TBRF) is a zoonotic disease caused by spirochetes of the genus Borrelia. This disease is underdiagnosed in our area due to a low index of suspicion among clinicians, as well as its difficult diagnosis. This study aims to present our experience in the diagnosis and therapeutic management of TBRF and a literature review. METHODS: A retrospective medical chart review was carried out on children diagnosed of TBRF from 2002 to 2012 in our hospital, and included clinical, epidemiological, microbiological, treatment, and outcome data. RESULTS: Nine children with TBRF were identified. Median age was 11 years. All cases occurred during warm months. The most frequent presenting clinical findings were fever, chills, headache, vomiting, myalgia and abdominal pain. Meningeal involvement was identified in 2 cases. In the case of 2 patients, Borrelia infection was identified in several relatives at the time of diagnosis. Mean C-protein reactive was 187 mg/L, and low platelet counts were observed in 56% of the cases. Borreliaspp. was visualized in peripheral blood smears in 67% of cases. All of the patients received antibiotic treatment. Doxycycline was used in children older than 8 years and erythromycin and penicillin in the younger ones. Jarisch-Herxheiner reaction occurred in one patient. All cases resolved without sequelae. CONCLUSIONS: We emphasize the importance of maintaining a high level of suspicion in endemic regions of TBRF. Early diagnosis and a correct therapy can prevent the appearance of subsequent fever recurrences and potential complications.

MRI characteristics of globus pallidus infarcts in isolated methylmalonic acidemia.

BACKGROUND: Bilateral infarcts confined to the globus pallidus are unusual and occur in conjunction with only a few disorders, including isolated methylmalonic acidemia, a heterogeneous inborn error of metabolism. On the basis of neuroradiographic features of metabolic strokes observed in a large cohort of patients with methylmalonic acidemia, we have devised a staging system for methylmalonic acidemia-related globus pallidus infarcts. MATERIALS AND METHODS: Forty patients with isolated methylmalonic acidemia and neurologic symptoms underwent clinical brain MR imaging studies, which included 3D-T1WI. Infarcted globus pallidus segments were neuroanatomically characterized, and infarct volumes were measured. RESULTS: Globus pallidus infarcts were present in 19 patients; all were bilateral, and most were left-dominant. A neuroanatomic scoring system based on the infarct patterns was devised; this revealed a 5-stage hierarchical susceptibility to metabolic infarct, with the posterior portion of the globus pallidus externa being the most vulnerable. Globus pallidus infarct prevalence by methylmalonic acidemia class was the following: cblA (5/7, 71%), cblB (3/7, 43%), mut(o) (10/22, 45%), and mut- (1/4, 25%). Tiny lacunar infarcts in the pars reticulata of the substantia nigra, previously unrecognized in methylmalonic acidemia, were found in 17 patients, 13 of whom also had a globus pallidus infarct. CONCLUSIONS: The staged pattern of globus pallidus infarcts in isolated methylmalonic acidemia suggests a nonuniform, regionally specific cellular susceptibility to metabolic injury, even for patients having milder biochemical phenotypes. In support of this hypothesis, the delineation of lacunar infarcts in the pars reticulata of the substantia nigra, a tissue functionally and histologically identical to the globus pallidus interna, supports the concept of cell-specific pathology.

Cytotoxic effect of double emulsion (w/o/w) cuso4 loaded pla nanoparticles on mkn-45 gastric adenocarcinoma cell line / Efecto citotóxico de nanopartículas de pla de doble emulsión (w/o/w) cargadas con cuso4 sobre la línea célular de adenocarcinoma gástrico mkn-45

Poly (L-lactic acid) (PLA) nanoparticles have the approval of the main institutions for drugs administration and therapeutics. However, the use of lactic acid polymer is controversial because lactic acid has been proposed as an energy source for cancer cells. The aim of this study was to evaluate the cytotoxic, apoptotic and cell cycle properties of PLA and CuSO4-loaded PLA biodegradable nanoparticles on MKN-45 gastric adenocarcinoma cell line. PLA nanoparticles for the delivery of the anticancer active principle CuSO4 were obtained using the double emulsion method. PLA and CuSO4 loaded PLA nanoparticles were morphologically characterized and their size determined using transmission electron microscopy (TEM). The cytotoxicity of this drug delivery system was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; apoptosis was evaluated using YO-PRO-1/Propidium Iodide and cell cycle analysis throughout flow cytometry. CuSO4-loaded PLA nanoparticles were effective inhibitors of MKN45 cancer cell growth. They increased cytotoxicity and apoptosis, and induced G1/Go cell cycle arrest;whereas the anticancer activity was increased using a 96 h treatment of a minimal (1mM) concentration of CuSO4 loaded in 40 µM PLA nanoparticles. The treatment with 40 µM lactic acid and PLA (40 µM) did not increase the rate of cell survival assays related to the control, which indicate that PLA use as a polymer carrier not induce proliferation of MKN-45 cancer cells. Our research presents novel data about the effect of PLA nanoparticles and CuSO4 on gastric cancer cell line MKN45.

Las nanopartículas de ácido poli L-láctico (PLA) tienen la aprobación de las principales instituciones de administración de medicamentos y terapéutica. Sin embargo, el uso de polímero de ácido láctico es controvertido ya que el ácido láctico se ha propuesto como una fuente de energía para las células cancerosas. El objetivo de este estudio fue evaluar las propiedades citotóxicas, la apoptosis y sobre el ciclo celular de las nanoparticulas de PLA biodegradable y de estas PLA nanopartículas cargadas con CuSO4 en la línea celular de adenocarcinoma gástrico MKN-45. Las nanopartículas de PLA para la administración del principio activo CuSO4 contra el cáncer se obtuvieron utilizando el método de doble emulsión. Las nanopartículas de PLA y PLA cargadas con CuSO4 se caracterizan morfológicamente y su tamaño fue determinaron usando microscopía electrónica de transmisión (TEM). Se evaluó la citotoxicidad de este sistema de administración de fármacos utilizando la 3 - (4,5-dimetiltiazol-2-il) -2,5-ensayo difeniltetrazolio (MTT); la apoptosis se evaluó usando yoduro de propidio/YO-PRO-1 y el análisis de ciclo celular por citometría de flujo. Las nanopartículas cargadas con CuSO4-PLA fueron eficaces inhibidores del crecimiento de las células MKN-45 cancerosas. Aumentaron citotoxicidad y la apoptosis, e inducen la detención del ciclo celular en G1/Go, mientras que la actividad contra el cáncer se incrementó con el uso de un tratamiento de 96 horas con una concentración mínima (1 mM) de CuSO4 cargado en nanopartículas con 40 µM de PLA. El tratamiento con 40 µM de ácido láctico y 40 µM PLA no aumentó la tasa de supervivencia de células en relación con el control, lo que indica que el uso de PLA como un polímero portador que no induce la proliferación de células de cáncer MKN-45. Nuestro estudio presenta nuevos datos sobre el efecto de las nanopartículas de PLA con CuSO4 en la línea celular de cáncer gástrico MKN-45.

La esclerosis múltiple en el embarazo: reporte de tres casos en el Hospital Universitario de San Ignacio (HUSI) / Multiple Sclerosis in Pregnancy

Introducción: Se presentan tres casos de pacientes con esclerosis múltiple (EM),diagnosticadas previo al embarazo, y que fueron evaluadas en la Unidad de MedicinaMaterno-Fetal durante sus controles y parto en el Hospital Universitario de SanIgnacio, centro de referencia nivel IV que atiende población embarazada de altoriesgo obstétrico perteneciente al régimen contributivo. Objetivo: Describir lasformas de presentación, fisiopatología, etiología y cuadro clínico de la EM, así comosu comportamiento en el embarazo. Metodología: Se realizó una búsqueda de laliteratura en las bases PubMed, Medline y Cochrane utilizando las palabras clave, pararecopilar información tanto en inglés como en español desde el 2000 al 2011. Despuésse eligieron artículos de revisión y de investigación en EM y embarazo. Conclusiones:Las pacientes con diagnóstico de EM en el embarazo parecen tener un menor riesgode sufrir una recaída, especialmente durante el último trimestre. Sin embargo, vieneseguido de una alta probabilidad de recaída durante los tres meses posteriores, comose observó en dos de los casos descritos en este estudio...

Introduction: Three cases of patients withmultiple sclerosis (MS), diagnosed before pregnancy,and were evaluated at the Departmentof Maternal-Fetal and birth control during theHospital Universitario San Ignacio, level IV referralcenter serving pregnant population highrisk obstetric pertaining to contributory scheme.Objective: To describe the clinical presentationsof the pathophysiology, etiology and clinicalfeatures of MS, as well as their behavior duringpregnancy. Methodology: Electronic search wasconducted in PubMed, Medline, and Cochraneusing the keywords to collect information inboth English and Spanish from 2000 to 2011. Afterreview articles were selected and research inmultiple sclerosis and pregnancy. Conclusions:There seems to be a lower risk of relapse duringpregnancy and especially during the last quarter.However, it is followed by a high probability ofrelapse within three months, as observed in twocases described in this study...

[Spurious hypoxemia due to hyperleukocytosis. Report of one case]. / Hipoxemia espuria por hiperleucocitosis. Reporte de un caso y revisión de la literatura.

BACKGROUND: Arterial gasometry is considered the gold standard for establishing a diagnosis of respiratory failure of any etiology. However, there are some circumstances in which it loses specificity, making necessary to consider other tests such as pulse oximetry to adequately determine hypoxemia. We report a 67 years old patient with sudden hypoacusia, right hemiparesis and polypnea. His laboratory exams on admission, showed extreme hypoxemia in several readings, without correlation to the patient's clinical condition nor the pulse oximetry, and a leukocytosis of 800.000 cells x ml, with many immature cells. Chronic myeloid leukemia was diagnosed and treatment with hydroxyurea was initiated, achieving normalization in the arterial gases in accordance with the fall of the white cell count. Interpretation of laboratory findings according to the general clinical context of the patient allowed to suspect a spurious hypoxemia, saving the patient from unnecessary and risky interventions.

Hipoxemia espuria por hiperleucocitosis: Reporte de un caso y revisión de la literatura / Spurious hypoxemia due to hyperleukocytosis: Report of one case

Background: Arterial gasometry is considered the gold standard for establishing a diagnosis of respiratory failure of any etiology. However, there are some circumstances in which it loses specificity, making necessary to consider other tests such as pulse oximetry to adequately determine hypoxemia. We report a 67 years old patient with sudden hypoacusia, right hemiparesis and polypnea. His laboratory exams on admission, showed extreme hypoxemia in several readings, without correlation to the patient's clinical condition nor the pulse oximetry, and a leukocytosis of 800.000 cells x ml, with many immature cells. Chronic myeloid leukemia was diagnosed and treatment with hydroxyurea was initiated, achieving normalization in the arterial gases in accordance with the fall of the white cell count. Interpretation of laboratory findings according to the general clinical context of the patient allowed to suspect a spurious hypoxemia, saving the patient from unnecessary and risky interventions.