Mapping and targeted viral activation of pancreatic nerves in mice reveal their roles in the regulation of glucose metabolism.

A lack of comprehensive mapping of ganglionic inputs into the pancreas and of technology for the modulation of the activity of specific pancreatic nerves has hindered the study of how they regulate metabolic processes. Here we show that the pancreas-innervating neurons in sympathetic, parasympathetic and sensory ganglia can be mapped in detail by using tissue clearing and retrograde tracing (the tracing of neural connections from the synapse to the cell body), and that genetic payloads can be delivered via intrapancreatic injection to target sites in efferent pancreatic nerves in live mice through optimized adeno-associated viruses and neural-tissue-specific promoters. We also show that, in male mice, the targeted activation of parasympathetic cholinergic intrapancreatic ganglia and neurons doubled plasma-insulin levels and improved glucose tolerance, and that tolerance was impaired by stimulating pancreas-projecting sympathetic neurons. The ability to map the peripheral ganglia innervating the pancreas and to deliver transgenes to specific pancreas-projecting neurons will facilitate the examination of ganglionic inputs and the study of the roles of pancreatic efferent innervation in glucose metabolism.

Clinical characteristics and outcome of hospitalized elderly patients with COVID- 19 after vaccine failure.

We described clinical characteristics and outcome of 160 patients over 65 years (01 September to 31 August 2021) who had a first positive SARS-CoV-2 PCR- test more than 14 days after full vaccination and were hospitalized with COVID-19. Median age of included patients was 84 years, 61.2% were over 80 years; 50.6% were male and most (82.5%) has at least one comorbidity. Up to 84% received specific treatment against COVID-19, including 76.9% low-flow oxygen therapy. We found that overall mortality was 25.6% and 30.6% in those older than 80 years. A higher mortality was significantly associated with older age and treatment with tocilizumab. Our data showed that although COVID-19 vaccines continue protecting elderly patients against hospitalization and death and might improve the prognosis after hospitalization in patients with breakthrough infections, mortality in this population -especially in those older than 80 years- remains very high.

Identification of genetic risk factors associated with ischaemic stroke in young Mexican patients.

BACKGROUND: Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. METHODS: We performed a case-control study of consecutive ischaemic stroke survivors aged ≤45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction-restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. RESULTS: 204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. CONCLUSION: The polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.

Epidermólisis bullosa en España: Estudio observacional de una cohorte de pacientes atendidos en un centro de referencia nacional / Epidermolysis Bullosa in Spain: Observational Study of a Cohort of Patients Treated in a National Referral Center

Antecedentes y objetivo La epidermólisis bullosa (EB) es un grupo heterogéneo de trastornos hereditarios caracterizado por un aumento de la fragilidad mucocutánea. El objetivo del presente estudio es describir las características clínicas y epidemiológicas de los pacientes con EB atendidos en el Hospital Universitario La Paz, centro de referencia nacional para EB hereditaria. Material y método Estudio observacional, retrospectivo y unicéntrico. Se incluyeron todos los pacientes con diagnóstico clínico y molecular de EB atendidos en el Servicio de Dermatología del Hospital Universitario La Paz desde el 1 de enero de 2000 hasta el 28 de febrero de 2021. Resultados Se registraron 214 pacientes, con una edad mediana de 17 años (RIQ: 8-32); el 54,2% fueron mujeres. Las formas clínicas correspondieron a EB distrófica con 135 (63,1%) casos, EB simple con 67 (31,3%) casos, EB juntural con ocho (3,7%), EB Kindler con tres (1,4%) casos y EB adquirida con un (0,5%) caso. El 35,5% de los pacientes procedían de Madrid. Las complicaciones clínicas más frecuentes en nuestra serie fueron el prurito (63,1%), las infecciones locales (56,5%) y el dolor (54,7%). Las complicaciones más graves fueron las cardíacas (5,6%) y la aparición de CCE (10,3%). Fallecieron 22 pacientes (10,3%). Conclusiones La forma clínica predominante fue la EBDR. Las complicaciones más prevalentes fueron el prurito, el dolor y las infecciones, y las más graves, la miocardiopatía y el CCE. Es un estudio pionero realizado en nuestro país que permitirá implementar estrategias para mejorar la situación sociosanitaria de los pacientes con EB (AU)

Background and objective Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by a high degree of mucocutaneous fragility. This study aimed to describe the clinical and epidemiologic characteristics of patients with EB treated in Hospital Universitario La Paz, a national referral center for inherited EB. Material and methods Observational, retrospective, single-center study. We included all cases with a clinical and molecular diagnosis of EB managed in the hospital's dermatology department from January 2, 2000, to February 28, 2021. Results A total of 214 cases were studied. The median (interquartile range) age was 17 (8–32) years; 54.2% were women. One hundred thirty-five (63.1%) patients had dystrophic EB, 67 (31.3%) had EB simplex, 8 (3.7%) had junctional EB, and 3 (1.4%) had Kindler syndrome. One (0.5%) had EB acquisita. Over a third (35.5%) of the patients resided in Madrid. The most common clinical complications were pruritus (63.1%), local infections (56.5%), and pain (54.7%). The most serious ones were cardiomyopathy (in 5.6%) and squamous cell carcinoma (10.3%). Twenty-two patients (10.3%) died. Conclusions Dystrophic EB was the most prevalent clinical form. The most prevalent complications were pruritus, pain, and infections. The most serious ones were cardiomyopathy and squamous cell carcinoma. This study is the first in Spain that explores strategies for improving the health status and quality of life of patients with EB (AU)

Spatial distribution of pyrogenic carbon in Iberian topsoils estimated by chemometric analysis of infrared spectra.

Understanding the global carbon (C) cycle is critical to accurately model feedbacks between climate and soil. Thus, many climate change studies focused on soil organic carbon (SOC) stock changes. Pyrogenic carbon (PyC) is one of the most stable fractions of soil organic matter (SOM). Accurate maps based on measured PyC contents are required to facilitate future soil management decisions and soil-climate feedback modelling. However, consistent measurements that cover large areas are rare. Therefore, this study aimed to map the PyC content and stock of the Iberian Peninsula, which covers contrasting climatic zones and has long-term data on wildfire occurrence. A partial least square (PLS) regression using the mid-infrared spectra (1800-400 cm-1) was applied to a dataset composed of 2961 soil samples from the Iberian component of the LUCAS 2009 database. The values of PyC for LUCAS points were modelled to obtain a map of topsoil PyC by a random forest (RF) approach using 36 auxiliary variables. The results were validated through comparison with documented historical wildfire activity and anthropogenic energy production. A strong relationship was found between these sources and the distribution of PyC. Our study estimates that the accumulated PyC in Iberian Peninsula soils comprises between 3.09 and 20.39% of total organic carbon (TOC) in the topsoil. Forests have higher PyC contents than grasslands, followed by agricultural soils. The incidence of recurrent wildfires also has a notable influence on PyC contents. This study shows the potential of estimating PyC with a single, rapid, low cost, chemometric method using new or archived soil spectra, and has the ability to improve soil-climate feedback modelling. It also offers a possible tool for measuring, reporting and verifying soil C stocks, which is likely to be important moving forward if soils are used as sinks for C sequestration.

Identificación de factores de riesgo genéticos asociados a la enfermedad vascular cerebral de tipo isquémico en jóvenes mexicanos / Identification of genetic risk factors associated with ischaemic stroke in young Mexican patients

Introducción: Diversos polimorfismos en genes candidatos que codifican proteínas del sistema hemostático se han propuesto como factores de riesgo para el desarrollo de trombosis.MétodosCasos y controles, sobrevivientes de enfermedad vascular cerebral (EVC) isquémica idiopática ≤ 45 años de edad del servicio de neurología incluidos de manera consecutiva de 2006 a 2014. Por PCR-RFLP se identificaron los polimorfismos: Thr325Ile y Ala147Thr del gen de TAFI, 4G/5G del gen de PAI-1, PLA1/A2 del gen de la glucoproteína plaquetaria IIb/IIIa, Glu298Asp del gen de eNOS, y C677T del gen de la 5,10 MTHFR. Se realizó un análisis multivariado de regresión logística para calcular el riesgo independiente de EVC.ResultadosDoscientos cuatro casos y 204 controles pareados por edad y sexo. Se asoció al polimorfismo Glu298Asp (genotipo p = 0,001 y frecuencia alélica p = 0,001), C677T (genotipo p = 0,01), hipertensión (p = 0,03) y tabaquismo (p = 0,02) con la presencia de EVC isquémico, no así para los polimorfismos Ala147Thr, Thr325IIe, 4G/5G y PLA1/A2. Se identificó como factor de riesgo independiente al alelo 298Asp (p = 0,03), T (p = 0,01), hipertensión (p = 0,03), tabaquismo (p = 0,01) y AHFEAT (p = 0,04).ConclusionesLos polimorfismos Glu298Asp y C677T de los genes que codifican a la enzima eNOS y 5,10 MTHFR, tabaquismo, hipertensión y AHFEAT se asociaron a la presencia de EVC isquémico en jóvenes mexicanos, no así el Thr325Ile, Ala147Thr, 4G/5G, PLA1/A2 en genes que codifican proteínas del sistema de fibrinólisis y receptores plaquetarios. (AU)

Introduction: Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis.MethodsWe performed a case-control study of consecutive ischaemic stroke survivors aged ≤ 45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke.Results204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P = .03), tobacco use (P = .02), and the polymorphisms Glu298Asp (genotype: P = .001, allele frequency: P = .001) and C677T (genotype: P = .01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P = .03) and T (P = .01) alleles, hypertension (P = .03), tobacco use (P = .01) and family history of stroke (P = .04) were identified as independent risk factors.ConclusionsThe polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors. (AU)

Epidermolysis Bullosa in Spain: Observational Study of a Cohort of Patients Treated in a National Referral Center. / Epidermólisis bullosa en España: Estudio observacional de una cohorte de pacientes atendidos en un centro de referencia nacional.

BACKGROUND AND OBJECTIVE: Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by a high degree of mucocutaneous fragility. This study aimed to describe the clinical and epidemiologic characteristics of patients with EB treated in Hospital Universitario La Paz, a national referral center for inherited EB. MATERIAL AND METHODS: Observational, retrospective, single-center study. We included all cases with a clinical and molecular diagnosis of EB managed in the hospital's dermatology department from January 2, 2000, to February 28, 2021. RESULTS: A total of 214 cases were studied. The median (interquartile range) age was 17 (8-32) years; 54.2% were women. One hundred thirty-five (63.1%) patients had dystrophic EB, 67 (31.3%) had EB simplex, 8 (3.7%) had junctional EB, and 3 (1.4%) had Kindler syndrome. One (0.5%) had EB acquisita. Over a third (35.5%) of the patients resided in Madrid. The most common clinical complications were pruritus (63.1%), local infections (56.5%), and pain (54.7%). The most serious ones were cardiomyopathy (in 5.6%) and squamous cell carcinoma (10.3%). Twenty-two patients (10.3%) died. CONCLUSIONS: Dystrophic EB was the most prevalent clinical form. The most prevalent complications were pruritus, pain, and infections. The most serious ones were cardiomyopathy and squamous cell carcinoma. This study is the first in Spain that explores strategies for improving the health status and quality of life of patients with EB.

Efecto de la psicoeducación en el afrontamiento y adaptación al rol de cuidador familiar del adulto mayor / Effect of psychoeducation in the support of the older adult family caregiver adaptation and coping role / Efeito da psicoeducação no enfrentamento e adaptação ao papel de cuidador familiar do idoso

Resumen Introducción: La transición demográfica y epidemiológica mundial, aunado a los avances en la ciencia y tecnología aplicados en mejorar la calidad de vida de la población, han influido en la longevidad; los individuos viven más, pero con un bienestar deficiente debido a las limitaciones y comorbilidades inherentes al envejecimiento, con las que a menudo necesitan el cuidado de alguien. Actualmente, uno de cada cuatro adultos mayores requiere de ayuda para realizar sus actividades de la vida diaria. Objetivo: Evaluar el efecto de una intervención de enfermería por medio de la psicoeducación para facilitar el proceso de afrontamiento y adaptación al rol de cuidador familiar del adulto mayor. Material y Métodos: Estudio cuantitativo, cuasi experimental, realizado en una unidad de medicina familiar, con un grupo de 70 cuidadores familiares de adultos mayores, los criterios de inclusión: adultos de 20 a 59 años que supieran leer y escribir. La intervención psicoeducativa consistió en 10 sesiones, los instrumentos aplicados pre y post intervención fueron la escala sobre el proceso de afrontamiento y adaptación, así como la que evalúa habilidad de cuidado. Se utilizó estadística descriptiva e inferencial. Resultados: La edad de los cuidadores familiares tuvo una media de 50.6, femeninos 92.8%. La intervención fue efectiva, pues se obtuvieron diferencias estadísticamente significativas entre el pre y post en afrontamiento y adaptación (X2 Mc nemar p=0.00001), así como para la habilidad de cuidado (X2 p=0.01), lo que sugiere un efecto positivo y sostenido de la intervención. Conclusiones: Los cuidadores familiares de los adultos mayores que participaron en la intervención, mostraron un efecto positivo en la adaptación a su rol de cuidador familiar.

Abstract Introduction: The present demographic transition, influenced by science and technology advances aimed at improving the quality of life, features a greater longevity; however, older adults sometimes suffer from limitations and comorbidities which are related to their aging process and which make them require caring assistance. Currently, around 25% of older adults require some kind of aid in order to perform their daily living activities. Objective: To assess the effect of a nursing intervention using psychoeducation to support the older adult family caregiver adaptation and coping role. Methods and materials: This is a quantitative quasi-experimental study carried out in a unit of family medicine with 70 family caregivers of older adults. The inclusion criteria was: adults aged 20 to 59 who could read and write. The intervention included 10 sessions. The pre and post applied instruments were the Coping Adaptation Processing Scale, and a scale to assess the ability to provide care. Descriptive and inferential statistics were calculated. Results: The mean age of the family caregivers was 50.6 years. 65 were female. The intervention turned out to be effective as statistically significant differences in coping and adaptation measures (X2 Mc Nemar p=0.00001), as well as caregiving abilities (X2 p=0.01) measures, were obtained at the post intervention assessment. Conclusion: The older adult family caregivers who participated in this nursing intervention showed a positive effect in their role.

Resumo Introdução: A transição demográfica e epidemiológica mundial, os avanços na ciência e tecnologia aplicados em melhorar a qualidade de vida da população, influenciam a longevidade; os indivíduos vivem mais, no entanto com um bem-estar deficiente, devido às limitações e comorbilidades inerentes ao envelhecimento, regularmente necessitam o cuidado de alguém. Atualmente, um de cada quatro idosos requerem de ajuda para realizar suas atividades da vida diária. Objetivo: Avaliar o efeito de uma intervenção de enfermagem através da psicoeducação para facilitar o processo de enfrentamento e adaptação no papel de cuidador familiar do idoso. Material e Métodos: Estudo quantitativo, quase experimental, realizado na unidade de medicina familiar, com um grupo de 70 cuidadores familiares de idosos, os critérios de inclusão: adultos de 20 a 59 anos, que soubessem ler e escrever. A intervenção psicoeducativa consistiu em 10 sessões, os instrumentos aplicados pre e post intervenção foram a escala sobre o processo de enfrentamento e adaptação, assim como a que avalia habilidade de cuidado. Utilizou-se estatística descritiva e inferencial. Resultados: A idade dos cuidadores familiares teve una média de 50.6, femininos 92.8%. A intervenção foi efetiva, pois se obtiveram diferenças estatisticamente significativas entre o pre e post em enfrentamento e adaptação (X2 Mc nemar p=0.00001), assim como, para a habilidade de cuidado (X2 p=0.01), o que sugere um efeito positivo e sustenido da intervenção. Conclusões: Os cuidadores familiares dos idosos que participaram na intervenção mostraram um efeito positivo na adaptação do seu papel de cuidador familiar.

Estandarización del manejo de accesos vasculares de hemodiálisis en el Hospital de Alta Especialidad de Yucatán / Standardization of vascular access management in hemodialysis in a High Specialty Hospital in Yucatan / Padronização do manejo de acessos vasculares de hemodiálises no Hospital de Alta Especialidade de Yucatán

Introducción: La calidad del cuidado de enfermería en la unidad de hemodiálisis del Hospital Regional de Alta Especialidad de la Península de Yucatán se fundamenta en el conocimiento científico, la evidencia clínica y la seguridad del paciente. Objetivo: Mejorar el cuidado del paciente con tratamiento hemodialítico y homogeneizar la práctica de enfermería. Métodos: Se diseñó un proyecto de intervención para estandarizar el manejo de los accesos vasculares mediante capacitación y cumplimiento del personal de enfermería. Se llevó a cabo de mayo-octubre del 2016, incluyó 12 enfermeros del área, quienes se evaluaron al inicio y al final, se les proporcionó una capacitación intermedia. Resultados: Los puntajes de la primera evaluación se ubicaban por debajo de los estándares de calidad, en el caso de las fístulas la puntuación obtenida fue de 27.58 puntos ± 2.64 y para los catéteres de 26.58 puntos ± 4.03; las fases más comprometidas en cada caso fueron la desconexión y la curación, respectivamente. Luego de la capacitación las puntuaciones mejoraron de forma considerable, la diferencia en las medias encontradas en el manejo de ambos accesos vasculares entre el antes y el después de la estandarización del procedimiento, fueron de t = -17.602, gl = 11, p = 0.000 para las fístulas y de t = -10.724, gl = 11, p = 0.000 para los catéteres. Conclusiones: Los resultados confirman la efectividad de la capacitación. Aún existen áreas de oportunidad, pero los resultados se han mantenido desde entonces, se gestionó la calidad y abastecimiento de los insumos, asimismo se han involucrado otras disciplinas en el proyecto.

Introduction: Nursing healthcare quality in the hemodialysis unit of the High Specialty Regional Hospital of Yucatan is based on the scientific knowledge, the clinical evidence, and the patient safety. Objective: To improve patient care under hemodialysis treatment and homogenize the corresponding nursing practice. Methods: An intervention project was designed to standardize the management of vascular access through nursing staff training and good performance. The initiative was carried out in May-October, 2016 and included 12 nurses of the area who were assessed pre and post an intermediate level training. Results: Scores in the first assessment were below the quality standards: fistulae related: 27.58 ±2.644, and catheter-related: 26.58 ±4.033. The most sensitive procedures in each case were disconnection and healing respectively. After the training, the related scores improved considerably -the mean differences found in the management of both vascular accesses before and after the standardization of the procedure were t = -17.602, gl = 11, P = .000 for fistulae related, and t = -10.724, gl = 11, P = .000 for catheter related. Conclusions: Results confirmed the effectiveness of the training, and the provision and quality of the supplies have been further fostered. Moreover, other disciplines have also been involved in this initiative.

Introdução: A qualidade do cuidado de enfermagem na unidade de hemodiálise do Hospital Regional de Alta Especialidade da Península de Yucatán fundamenta-se no conhecimento científico, a evidencia clínica e a segurança do paciente. Objetivo: Melhorar o cuidado do paciente com tratamento de hemodiálise e homogeneizar a prática de enfermagem. Métodos: Desenhou-se um projeto de intervenção para padronizar o manejo dos acessos vasculares mediante capacitação e cumprimento do pessoal de enfermagem. Levou-se a cabo de maio-outubro de 2016, incluiu 12 enfermeiros da área, quem se avaliou ao início e ao final, com uma capacitação intermédia. Resultados: A pontuação da primeira avaliação situava-se por embaixo dos estândares de qualidade, no caso das fístulas a pontuação obtida foi de 27.58 pontos ± 2.644 e para os cateteres de 26.58 pontos ± 4.033; as fases mais comprometidas em cada caso foram a desconexão e a cura, respectivamente. Logo da capacitação, as pontuações melhoraram de forma considerável, a diferença nas médias encontradas no manejo de ambos os acessos vasculares entre o antes e o depois da estandardização do procedimento, foram de t = -17.602, gl = 11, p = .000 para as fístulas e de t = -10.724, gl = 11, p = .000 para os cateteres. Conclusões: Os resultados confirmam a efetividade da capacitação. Ainda existem áreas de oportunidade, mas os resultados têm se mantido desde então, gerenciou-se a qualidade e abastecimento dos insumos, assim mesmo têm se envolvido outras disciplinas no projeto.

Experiencia en el diagnóstico molecular de neuropatías hereditarias en un hospital pediátrico de tercer nivel / Experience in molecular diagnostic in hereditary neuropathies in a pediatric tertiary hospital

Introducción. La enfermedad de Charcot-Marie-Tooth (CMT) es la neuropatía hereditaria sensitivomotora más frecuente. Avances en el diagnóstico molecular han incrementado las posibilidades diagnósticas de estos pacientes. Pacientes y métodos. Estudio retrospectivo de 36 casos pediátricos diagnosticados de CMT en un centro terciario en el período 2003-2015. Resultados. Se identificaron 16 pacientes con CMT1A por una duplicación en PMP22; dos casos se diagnosticaron de neuropatía hereditaria con predisposición a parálisis por presión, uno de ellos con una mutación puntual en PMP22; un varón con un fenotipo leve desmielinizante se diagnosticó de CMTX1 por mutación en GJB1; un paciente con una hipotonía paralítica en el nacimiento y un patrón axonal por mutación en MFN2; un paciente de origen rumano se diagnosticó de CMT4D por una mutación en el gen NDRG1; una paciente con una atrofia muscular espinal congénita distal con neuropatía axonal leve asociada por mutación en el gen TRPV4; tres niñas de una familia consanguínea de etnia gitana se diagnosticaron de CMT axonal con descargas neuromiotónicas por una mutación en el gen HINT1; 12 pacientes no tienen diagnóstico molecular actualmente, cuatro de ellos de etnia gitana. Conclusiones. CMT1A predominó en nuestra serie (44%), como corresponde a la bibliografía. Destacamos la descripción de una paciente con una mutación en TRPV4 recientemente descrita como causa de CMT2C y tres casos de una misma familia consanguínea gitana con la misma mutación en el gen HINT1 recientemente publicada como causa de neuropatía axonal con neuromiotonía autosómica recesiva (AR-CMT2). El porcentaje de casos sin diagnóstico molecular es similar al de grandes series europeas (AU)

Introduction. Charcot-Marie-Tooth (CMT) is the most common hereditary sensory motor neuropathy. Advances in molecular diagnosis have increased the diagnostic possibilities of these patients. Patients and methods. Retrospective study of 36 pediatric patients diagnosed with CMT in a tertiary center in 2003-2015. Results. We found 16 patients were diagnosed by a duplication in PMP22; two cases were diagnosed of hereditary neuropathy with liability to pressure palsies, one with a point mutation in PMP22; a male with a mild demyelinating phenotype, without family history, was diagnosed with GJB1 mutation; in a patient with a peripheral hypotonia at birth and axonal pattern in EMG by mutation in MFN2; a gypsy patient, with consanguineous family, CMT4D, was identified by a mutation in the gene NDRG1; a patient with multiplex congenital arthrogryposis and vocal cord paralysis, whose mother had a scapular-peroneal syndrome, had a congenital spinal muscular atrophy with mild distal axonal neuropathy by mutation in gene TRPV4; three girls, from a gypsy consanguineous family, with axonal CMT with neuromyotonic discharges were diagnosed by a mutation in the gene HINT1; twelve patients haven’t molecular diagnosis currently. Conclusions. CMT1A predominated in our series (44%), as previous studies. We emphasize the description of a patient with a mutation in TRPV4 recently described as a cause of CMT2C and three cases, of gypsy consanguineous family, with the same mutation in HINT1 gene, recently described as a cause of axonal neuropathy with neuromyotonia, autosomal recessive (AR-CMT2). The proportion of patients without molecular diagnosis is similar to main European series (AU)

[Experience in molecular diagnostic in hereditary neuropathies in a pediatric tertiary hospital]. / Experiencia en el diagnóstico molecular de neuropatías hereditarias en un hospital pediátrico de tercer nivel.

INTRODUCTION: Charcot-Marie-Tooth (CMT) is the most common hereditary sensory motor neuropathy. Advances in molecular diagnosis have increased the diagnostic possibilities of these patients. PATIENTS AND METHODS: Retrospective study of 36 pediatric patients diagnosed with CMT in a tertiary center in 2003-2015. RESULTS: We found 16 patients were diagnosed by a duplication in PMP22; two cases were diagnosed of hereditary neuropathy with liability to pressure palsies, one with a point mutation in PMP22; a male with a mild demyelinating phenotype, without family history, was diagnosed with GJB1 mutation; in a patient with a peripheral hypotonia at birth and axonal pattern in EMG by mutation in MFN2; a gypsy patient, with consanguineous family, CMT4D, was identified by a mutation in the gene NDRG1; a patient with multiplex congenital arthrogryposis and vocal cord paralysis, whose mother had a scapular-peroneal syndrome, had a congenital spinal muscular atrophy with mild distal axonal neuropathy by mutation in gene TRPV4; three girls, from a gypsy consanguineous family, with axonal CMT with neuromyotonic discharges were diagnosed by a mutation in the gene HINT1; twelve patients haven't molecular diagnosis currently. CONCLUSIONS: CMT1A predominated in our series (44%), as previous studies. We emphasize the description of a patient with a mutation in TRPV4 recently described as a cause of CMT2C and three cases, of gypsy consanguineous family, with the same mutation in HINT1 gene, recently described as a cause of axonal neuropathy with neuromyotonia, autosomal recessive (AR-CMT2). The proportion of patients without molecular diagnosis is similar to main European series.

TITLE: Experiencia en el diagnostico molecular de neuropatias hereditarias en un hospital pediatrico de tercer nivel.Introduccion. La enfermedad de Charcot-Marie-Tooth (CMT) es la neuropatia hereditaria sensitivomotora mas frecuente. Avances en el diagnostico molecular han incrementado las posibilidades diagnosticas de estos pacientes. Pacientes y metodos. Estudio retrospectivo de 36 casos pediatricos diagnosticados de CMT en un centro terciario en el periodo 2003-2015. Resultados. Se identificaron 16 pacientes con CMT1A por una duplicacion en PMP22; dos casos se diagnosticaron de neuropatia hereditaria con predisposicion a paralisis por presion, uno de ellos con una mutacion puntual en PMP22; un varon con un fenotipo leve desmielinizante se diagnostico de CMTX1 por mutacion en GJB1; un paciente con una hipotonia paralitica en el nacimiento y un patron axonal por mutacion en MFN2; un paciente de origen rumano se diagnostico de CMT4D por una mutacion en el gen NDRG1; una paciente con una atrofia muscular espinal congenita distal con neuropatia axonal leve asociada por mutacion en el gen TRPV4; tres niñas de una familia consanguinea de etnia gitana se diagnosticaron de CMT axonal con descargas neuromiotonicas por una mutacion en el gen HINT1; 12 pacientes no tienen diagnostico molecular actualmente, cuatro de ellos de etnia gitana. Conclusiones. CMT1A predomino en nuestra serie (44%), como corresponde a la bibliografia. Destacamos la descripcion de una paciente con una mutacion en TRPV4 recientemente descrita como causa de CMT2C y tres casos de una misma familia consanguinea gitana con la misma mutacion en el gen HINT1 recientemente publicada como causa de neuropatia axonal con neuromiotonia autosomica recesiva (AR-CMT2). El porcentaje de casos sin diagnostico molecular es similar al de grandes series europeas.

Mastitis granulomatosa / Granulomatous mastitis

La mastitis granulomatosa es una rara enfermedad de la mama de tipo inflamatorio, de causa desconocida, que se encuentra en pacientes premenopáusicas. Las características clínicas y radiológicas son similares a la de la tuberculosis y al carcinoma de mama, por lo que el clínico debe tenerla presente sobre todo al obtener cultivos persistentemente negativos y/o biopsias no concluyentes, y siempre descartando otras patologías antes de iniciar un tratamiento. El hallazgo clínico más frecuente es el de un bulto en la mama, que suele ser unilateral y de características inflamatorias. Se debe ser cuidadoso al hacer el diagnóstico para evitar que estas pacientes sean sometidas a mastectomía por error. La biopsia excisional para una evaluación histopatológica esta recomendada en todos los casos. El diagnóstico histológico está caracterizado por una lobulitis necrosante granulomatosa crónica con microabscesos. Entre de los tratamientos que han sido utilizados, se encuentran la escisión quirúrgica, corticoterapia, antibioticoterapia y metotrexato (MTX), con eficacia variable. La modalidad de tratamiento inicial preferida es antibioticoterapia previa a los corticoides. Sin embargo, el método más apropiado aún parece poco claro. Se recomienda un seguimiento a largo plazo por el alto índice de recurrencias que presenta esta enfermedad. Presentamos el caso de una mastitis granulomatosa en la que se han usado corticoides inicialmente y posteriormente se reforzó con MTX, con remisión completa de la misma

Granulomatous mastitis is a rare inflammatory disease of the breast with no known cause that occurs in premenopausal women. The clinical and radiological features are similar to those of tuberculosis and breast carcinoma and consequently clinicians should consider this diagnosis in patients with persistently negative cultures and/or inconclusive biopsies. Other diseases should always be excluded before treatment is begun. The most frequent clinical finding is a lump in the breast. These lumps are usually unilateral and inflammatory. Correct diagnosis is essential to ensure that these patients do not undergo an unnecessary mastectomy. Excisional biopsy for histopathological analysis is recommended in all patients. Histological diagnosis is characterized by chronic necrotizing granulomatous lobulitis with microabscesses. Treatments include surgical excision, corticosteroids, antibiotics, and methotrexate, with variable efficacy. The preferred initial treatment is antibiotic therapy prior to steroids but the most appropriate method remains unclear. Long-term monitoring is recommended due to the high recurrence rate of the disease. We present a case a granulomatous mastitis that was initially treated with corticosteroids and subsequently by methotrexate, with complete remission of the disease

Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer.

Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).

Cardiotrophin 1 protects beta cells from apoptosis and prevents streptozotocin-induced diabetes in a mouse model.

AIMS/HYPOTHESIS: Cardiotrophin 1 (CT-1) is a recently described cytokine originally isolated from the heart where it has been shown to play an important role in apoptotic protection of cardiomyocytes and heart hypertrophy. Its beneficial properties have also been described in other organs such as liver and neuromuscular tissue. In the present study, we investigated whether CT-1 can confer protection against pro-apoptotic stimuli in pancreatic beta cells, and its role in insulin secretion and diabetes development. METHODS: The effects of CT-1 on apoptosis and function were studied using MIN6B1 cells and freshly isolated murine pancreatic islets. The impact on the development of diabetes was evaluated in Ct1-null (Ct1 (-/-)) mice (the gene Ct1 is also known as Ctf1) using two streptozotocin (STZ)-induced models of diabetes. RESULTS: CT-1 has a protective effect in MIN6B1 cells and murine islets under the pro-apoptotic stimulus of serum deprivation, which correlates with the expression of B cell lymphoma-extra large, or following exposure to a mixture of cytokines. In addition, CT-1 enhances glucose-stimulated insulin secretion in MIN6B1 cells and this was repressed by inhibitors of phospholipase C. Furthermore, Ct1 (-/-) mice were more prone to develop diabetes, and their glucose tolerance test showed impaired plasma glucose clearance which correlated with decreased pancreatic insulin secretion. CONCLUSIONS/INTERPRETATION: The results obtained from both in vitro and in vivo experiments show that CT-1 improves beta cell function and survival, and protects mice against STZ-induced diabetes.

[Application of the motor unit number estimation (MUNE-Poisson) statistical technique in patients with neurogenic processes]. / Aplicación en pacientes con procesos neurogénicos de la técnica estadística de estimación del número de unidades motoras (MUNE-Poisson).

INTRODUCTION: Little research has been conducted on applying the statistical estimation of the number of motor units (the MUNE statistic) in the diagnosis of neurogenic processes. AIMS: To determine the sensitivity of this test in patients with different neurogenic processes and to disseminate and clarify its basic methodological aspects. SUBJECTS AND METHODS: Both the conventional calculation and the modified version of the MUNE-Poisson put forward by Shefner et al (MUNEm) were used to carry out unilateral studies of the extensor digitorum brevis muscle in 82 patients who had previously been clinically and electromyographically diagnosed with sensory-motor axonal polyneuropathy (36 cases), unilateral L5 radiculopathy (26 patients) and second motor neuron disease (20 cases). RESULTS: Overall sensitivity of the two methods was 81.7% and 82.9%, respectively, with no significant differences between them. Similarly, the sensitivity of the MUNE studies does not differ statistically according to the diagnosis. Patients who had a compound muscle action potential (CMAP) with a reduced amplitude displayed significantly higher sensitivity in MUNE studies (94.8%) than those who exhibited a normal CMAP (69.7%) (p < 0.001). CONCLUSIONS: Although routine use of the MUNE statistical method is unnecessary in daily practice, it should be considered for use in processes in which conventional muscle electromyography, especially involving distal ones, offers doubtful results or the aim is to follow the progression of certain neurogenic processes.

Aplicación en pacientes con procesos neurogénicos de la técnica estadística de estimación del número de unidades motoras (MUNE-Poisson) / Application of the motor unit number estimation (mune-poisson) statistical technique in patients with neurogenic processes

Introducción. Existe poca experiencia sobre la aplicación de la estimación estadística del número de unidades motoras (MUNE estadístico) en el diagnóstico de procesos neurogénicos. Objetivos. Determinar la sensibilidad de dicho test en pacientes con distintos procesos neurogénicos y difundir y aclarar los aspectos metodológicos fundamentales de aquél. Sujetos y métodos. Se ha estudiado mediante MUNE-Poisson, utilizando el calculo convencional y el modificado propuesto por Shefner et al (MUNEm), unilateralmente el músculo extensor digitorum brevis de 82 pacientes previamente diagnosticados clínica y electromiográficamente de polineuropatía axonal sensitivomotora (36 casos), radiculopatía L5 unilateral (26 pacientes) y enfermedad de la segunda motoneurona (20 casos). Resultados. La sensibilidad global de ambos métodos ha sido de 81,7 y 82,9%, respectivamente, sin diferencias significativas entre ellos. La sensibilidad de los estudios MUNE tampoco es estadísticamente diferente según el diagnóstico. Los pacientes que presentaron amplitud del potencial muscular compuesto (CMAP) reducida en amplitud mostraron significativamente mayor sensibilidad en los estudios MUNE (94,8%) que los que exhibieron un CMAP normal (69,7%) (p < 0,001). Conclusión. Aunque es innecesario utilizar rutinariamente en la práctica diaria el método MUNE estadístico, sí se debe considerar su empleo en procesos en los que la electromiografía convencional de músculos, sobre todo distales, presenta resultados dudosos, o se pretende seguir la evolución de ciertos procesos neurogénicos

Introduction. Little research has been conducted on applying the statistical estimation of the number of motor units (the MUNE statistic) in the diagnosis of neurogenic processes. Aims. To determine the sensitivity of this test in patients with different neurogenic processes and to disseminate and clarify its basic methodological aspects. Subjects and methods. Both the conventional calculation and the modified version of the MUNE-Poisson put forward by Shefner et al (MUNEm) were used to carry out unilateral studies of the extensor digitorum brevis muscle in 82 patients who had previously been clinically and electromyographically diagnosed with sensory-motor axonal polyneuropathy (36 cases), unilateral L5 radiculopathy (26 patients) and second motor neuron disease (20 cases). Results. Overall sensitivity of the two methods was 81.7% and 82.9%, respectively, with no significant differences between them. Similarly, the sensitivity of the MUNE studies does not differ statistically according to the diagnosis. Patients who had a compound muscle action potential (CMAP) with a reduced amplitude displayed significantly higher sensitivity in MUNE studies (94.8%) than those who exhibited a normal CMAP (69.7%) (p < 0.001). Conclusions. Although routine use of the MUNE statistical method is unnecessary in daily practice, it should be considered for use in processes in which conventional muscle electromyography, especially involving distal ones, offers doubtful results or the aim is to follow the progression of certain neurogenic processes

Patch-clamp 'mapping' of ion channel activity in human sperm reveals regionalisation and co-localisation into mixed clusters.

Ion channels are pivotal to many aspects of sperm physiology and function. We have used the patch clamp technique to investigate the distribution of ion channels in the plasma membrane of the head of human spermatozoa. We report that three types of activity are common in the equatorial and acrosomal regions of the sperm head. Two of these (a chloride-permeable anion channel showing long stable openings and a second channel which flickered between open and closed states and was dependent upon cytoplasmic factors for activity) were localised primarily to the equatorial segment. A third type, closely resembling the flickering activity but with different voltage sensitivity of P(open), was more widely distributed but was not detectable over the anterior acrosome. In the anterior acrosomal area channels were present but showed very low levels of spontaneous activity. A unique feature of channel activity in the sperm equatorial region was co-localisation into mixed clusters, most patches were devoid of activity but 'active' patches typically contained two or more types of activity (in a single 200-300 nM diameter patch). We conclude that ion channels in the sperm membrane show regionalisation of type and activity and that the channels are clustered into functional groups, possibly interacting through local effects on membrane potential.

Giant hypothalamic hamartoma and dacrystic seizures.

Ictal crying is a rare type of epileptic seizure associated with hypothalamic hamartoma and with other lesions such as tumours, vascular malformations, hippocampal sclerosis, or cerebral infarction. We describe the case of an infant with gelastic, dacrystic and other types of seizures associated with a giant hypothalamic hamartoma, and present a video sequence of dacrystic seizures. Dacrystic episodes presented in clusters at sleep onset, initially in the form of moaning followed by face-flushing that rapidly evolved to crying, associated with a lateral and upper deviation of both eyeballs, along with clonic aspects of the eyelids. After a few seconds, the crying became less intense, she stared, and oro-alimentary automatisms became prominent along with some slow horizontal movements of the eyes and the head. Following surgery, at the age of nine months, the gelastic seizures stopped, but dacrystic seizures persisted. [Published with video sequences].

Radiología simple en el síndrome de latigazo cervical / Plain-X-rays in the cervical whisplash syndrome

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