Human Alzheimer's disease gene expression signatures and immune profile in APP mouse models: a discrete transcriptomic view of Aß plaque pathology.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease with pathological hallmarks including the formation of extracellular aggregates of amyloid-beta (Aß) known as plaques and intracellular tau tangles. Coincident with the formation of Aß plaques is recruitment and activation of glial cells to the plaque forming a plaque niche. In addition to histological data showing the formation of the niche, AD genetic studies have added to the growing appreciation of how dysfunctional glia pathways drive neuropathology, with emphasis on microglia pathways. Genomic approaches enable comparisons of human disease profiles between different mouse models informing on their utility to evaluate secondary changes to triggers such as Aß deposition. METHODS: In this study, we utilized two animal models of AD to examine and characterize the AD-associated pathology: the Tg2576 Swedish APP (KM670/671NL) and TgCRND8 Swedish plus Indiana APP (KM670/671NL + V717F) lines. We used laser capture microscopy (LCM) to isolate samples surrounding Thio-S positive plaques from distal non-plaque tissue. These samples were then analyzed using RNA sequencing. RESULTS: We determined age-associated transcriptomic differences between two similar yet distinct APP transgenic mouse models, known to differ in proportional amyloidogenic species and plaque deposition rates. In Tg2576, human AD gene signatures were not observed despite profiling mice out to 15 months of age. TgCRND8 mice however showed progressive and robust induction of lysomal, neuroimmune, and ITIM/ITAM-associated gene signatures overlapping with prior human AD brain transcriptomic studies. Notably, RNAseq analyses highlighted the vast majority of transcriptional changes observed in aging TgCRND8 cortical brain homogenates were in fact specifically enriched within the plaque niche samples. Data uncovered plaque-associated enrichment of microglia-related genes such as ITIM/ITAM-associated genes and pathway markers of phagocytosis. CONCLUSION: This work may help guide improved translational value of APP mouse models of AD, particularly for strategies aimed at targeting neuroimmune and neurodegenerative pathways, by demonstrating that TgCRND8 more closely recapitulates specific human AD-associated transcriptional responses.

Survey of neonatal resuscitation practices showed post-training improvements but need to reinforce preterm management, monitoring and adrenaline use.

AIM: Neonatal resuscitation surveys have showed practice variations between countries, centres and levels of care. We evaluated delivery room practices after a nationwide neonatal resuscitation training programme focused on nontertiary centres. METHODS: A 2012 survey sent to all Spanish hospitals handling deliveries covered staff availability and training, equipment and practices in the delivery room and during transfers to neonatal intensive care units. The results from 98 centres that had completed a previous survey in 2007 were analysed by levels of care. Pearson's chi-square test was used to compare the proportions. RESULTS: The following had significantly improved in 2012 compared to 2007: the availability of T-piece resuscitators (71.4% vs. 41.8%), plastic wraps (69.4% vs. 31.6%), gas blenders (79.6% vs. 40.8%), pulse oximetry (92.9% vs. 61.2%), use of continuous positive airway pressure (82.7% vs. 43.9%) (all p < 0.01), the availability of instructors (55.6% vs. 83.3%, p < 0.05) and neonatal resuscitation courses (40.8% vs. 79.6%, p < 0.05) in nontertiary centres. In 2012, the use of exhaled carbon dioxide detectors was <7% and endotracheal administration of adrenaline was >90%. CONCLUSION: Neonatal resuscitation equipment and practices improved over time, but several aspects needed to be reinforced in training programmes, namely preterm infants' management, monitoring and adrenaline administration.

Mammary analogue secretory carcinoma of the salivary glands.

Background: Mammary analogue secretory carcinoma (MASC) is a new disease among tumours affecting the salivary glands. It was first reported in 2010, and few cases have been reported worldwide. MASC is often incorrectly diagnosed as salivary gland acinic cell carcinoma. We present here the case of a patient with an asymptomatic parotid tumour who underwent a parotidectomy of the superficial lobe. Case report: A 78-year-old female patient came to the clinic for a tumour of approximately 2.5 × 2.5 cm and a hard, elastic consistency that had grown insidiously in the right preauricular region. Magnetic resonance imaging of the head and neck showed a heterogeneous ovoid lesion located in the lower part of the superficial lobe of the right parotid gland, measuring 29 × 27 × 27 mm. A superficial parotidectomy was performed with the facial nerve identified and preserved. Immunohistochemistry was positive for S100, mammaglobin, periodic acid Schiff (PAS) and GATA-3. Fluorescence in situ hybridisation analysis was subsequently performed and Translocation-ETS-Leukemia Virus (ETV6) gene rearrangement observed. These findings were consistent with diagnosis of a MASC. The patient then required no new interventions or adjuvant therapy. At publication, she was free of disease and continues in clinical follow-up. Conclusion: MASC is a tumour of the saliva glands that is recently described and rare. There are no studies that describe its biological behaviour or prognosis precisely.

Intraosseous mucoepidermoid carcinoma of the mandible.

Background: Mucoepidermoid carcinoma starts in the salivary glands and accounts for 5%-10% of all salivary gland tumours. Its intraosseous occurrence is rare and only accounts for 2%-3% of all mucoepidermoid carcinomas. This neoplasm often follows a long and indolent course. Also, given its ambiguous presentation and similarities to other dental pathologies, it often has a late diagnosis. In this instance, we present the case of a patient with an asymptomatic mandibular lesion, who underwent mandibular resection and reconstruction with fibula free flap. Case report: A 32-year-old male patient reported discomfort when chewing, which was attributable to a self-detected mass localised in proximity to teeth 47 and 48. The lesion presented as a slight swelling without clear expression in the oral cavity mucosa. The rest of the physical examination revealed no abnormalities. Both the panoramic radiograph and computed tomography of the maxillary bones revealed lytic lesions in proximity to teeth 47 and 48, close to the mandibular angle. An incisional biopsy was performed, for which the pathological anatomy showed low-grade mucoepidermoid carcinoma. A resection was then performed, which involved a right hemimandibulectomy with ipsilateral cervical lymphadenectomy. The reconstruction was performed with a right fibula-free flap. Upon histological evaluation of the surgical specimen, an intermediate-grade mucoepidermoid carcinoma was found. The patient presented good post-operative evolution. Following a multidisciplinary assessment, the use of adjuvant radiation therapy was deemed necessary. The patient currently presents good evolution and has regular check-ups. Conclusion: Intraosseous mucoepidermoid carcinoma is a rare salivary gland tumour. Given its low frequency, there are no studies that accurately describe its biological behaviour and prognosis.

Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model.

Brain derived neurotrophic factor (BDNF) promotes the growth, differentiation, maintenance and survival of neurons. These attributes make BDNF a potentially powerful therapeutic agent. However, its charge, instability in blood, and poor blood brain barrier (BBB) penetrability have impeded its development. Here, we show that engineered clathrin triskelia (CT) conjugated to BDNF (BDNF-CT) and delivered intranasally increased hippocampal BDNF concentrations 400-fold above that achieved previously with intranasal BDNF alone. We also show that BDNF-CT targeted Tropomyosin receptor kinase B (TrkB) and increased TrkB expression and downstream signaling in iTat mouse brains. Mice were induced to conditionally express neurotoxic HIV Transactivator-of-Transcription (Tat) protein that decreases BDNF. Down-regulation of BDNF is correlated with increased severity of HIV/neuroAIDS. BDNF-CT enhanced neurorestorative effects in the hippocampus including newborn cell proliferation and survival, granule cell neurogenesis, synaptogenesis and increased dendritic integrity. BDNF-CT exerted cognitive-enhancing effects by reducing Tat-induced learning and memory deficits. These results show that CT bionanoparticles efficiently deliver BDNF to the brain, making them potentially powerful tools in regenerative medicine.

Rescue therapy with terlipressin by continuous infusion in a child with catecholamine-resistant septic shock.

A 2-month-old female infant presented with septic shock, refractory to high doses of catecholamines. Continuous infusion of terlipressin at a rate of 10 mcg/kgh produced a significant increase in the mean arterial pressure that was evident within half and hour, so allowing a reduction in the rate of catecholamine infusion. However, 18 h later, the blood pressure fell again and finally the patient died. This case shows the potential value of terlipressin infusion to restore normal mean arterial pressure in children with vasodilatory shock and hypotension refractory to catecholamines.

Rehabilitación vocal en un paciente con cáncer de laringe tratado con radioterapia / Vocal rehabilitation in a patient with laryngal cancer treated with radiotherapy / Reabilitação vocal em paciente com câncer de laringe tratado com radioterapia

INTRODUCCIÓN: La mayoría de la población con cáncer de laringe experimenta alteraciones persistentes en la voz por causa de los efectos fisiopatológicos de la radioterapia, provocando un gran impacto a nivel funcional y psicosocial. Los objetivos son: Determinar los momentos de la intervención fonoaudiológica en pacientes con cáncer de laringe tratados con radioterapia, describir la metodología de evaluación clínica y objetiva de la función fonatoria, identificar los factores que colaboran en la mejoría de la calidad vocal, comunicación y calidad de vida del paciente. MATERIAL Y MÉTODO: Diseño: Caso clínico. Paciente femenino, de 78 años con diagnóstico de carcinoma escamoso moderadamente diferenciado, infiltrante de laringe EI (T1bN0M0). Realizó radioterapia de intensidad modulada. Entrevista pre e intratratamiento, postratamiento de radioterapia y rehabilitación vocal propiamente dicha. Estudio objetivo de la voz (PRAAT). Valoración perceptual de la voz (GRBAS). Encuesta de calidad de vida (VHI).

INTRODUCTION: The majority of the population with laryngeal cancer experiences persistent alterations in the voice because of the pathophysiological effects of radiotherapy, provoking a great impact at functional and psychosocial level. The objectives are to determine the moments of the speech-language intervention in patients with laryngeal cancer treated with radiotherapy, describe the methodology of clinical and objective evaluation of phonatory function, identify the factors that contribute to the improvement of vocal quality, communication and quality of life of the patient. MATERIAL AND METHOD: Design: Clinical case. Female patient, 78 years old with diagnosis of moderately differentiated squamous carcinoma, infiltrating larynx EI (T1bN0M0). She performed modulated intensity radiotherapy. Pre and intra-treatment interview, post-treatment of radiotherapy and vocal rehabilitation proper. Objective study of voice (PRAAT). Perceptual perception of voice (GRBAS). Quality of Life Survey (VHI).

INTRODUÇÃO: A maioria da população com câncer de laringe sofre alterações persistentes na voz devido aos efeitos fisiopatológicos da radioterapia, causando um grande impacto no nível funcional e psicosocial. Os objetivos são determinar os momentos da intervenção fonoaudiológica em pacientes com câncer de laringe tratados com radioterapia, descreva a metodologia de avaliação clínica e objetiva da função fonatória, identificar os fatores que contribuem para a melhoria da qualidade vocal, comunicação e qualidade de vida do paciente. MATERIAL E MÉTODO: Design: Caso clínico. Paciente do sexo feminino, 78 anos com diagnóstico de carcinoma escamoso moderadamente diferenciado, infarto da laringe EI (T1bN0M0). Eu executo radioterapia de intensidade modulada. Entrevista pré e intra-tratamento, pós-tratamento de radioterapia e reabilitação vocal própria. Estudo objetivo da voz (PRAAT). Percepção perceptiva da voz (GRBAS). Inquérito à qualidade de vida (VHI)

Uso de Láser diodo de 1470 nm en el tratamiento del carcinoma escamoso de laringe (Tis, T1 y T2) en adultos mayores / 4170 nm diode Laser use in the treatment of laringeal squamous carcinoma (Tis, T1 and T2) in elderly adults / Usando diodo laser 1470 nm, no tratamento do carcinoma de celulas escamosas da laringe (Tis, T1 y T2) em idosos

Introducción: entre las diferentes modalidades terapéuticas para el carcinoma escamoso de laringe en estadios iniciales, la cirugía transoral láser (CTL) constituye el tratamiento de elección. El láser de CO2 es aceptado universalmente como la mejor herramienta terapéutica en este sentido. En situaciones de no poder acceder a esa tecnología, es posible utilizar otros instrumentos para resección en CTL (radiofrecuencia, electrobisturí). Entre estas, nuestro equipo de trabajo ha implementado el uso del láser de diodo de 1470 nm. En el presente trabajo describimos los resultados preliminares en el tratamiento de estadios tempranos del carcinoma escamoso de laringe con CTL. Materiales y métodos: Se utilizó el láser de diodo de 1470 nm en pacientes adultos mayores realizados entre enero de 2012 y diciembre de 2015 en el Servicio de Otorrinolaringología del Hospital Dr. C. Milstein. Resultados: Se trataron 32 pacientes con cáncer de laringe, de los cuales se incluyeron 21, todos mayores de 65 años, con carcinoma escamoso de laringe estadio Tis T1 y T2 sin compromiso cervical ni metastásico y sin tratamiento oncológico previo. De los 21 pacientes incluidos, a 19 se les realizó una única intervención y dos fueron reintervenidos con la misma técnica. Conclusiones: El uso del láser diodo de 1470 nm para el tratamiento del carcinoma escamoso de laringe en estadios iniciales ha permitido controlar la enfermedad en los 21 pacientes intervenidos con esta tecnología, en un tiempo medio de seguimiento de 21 meses. La CTL con láser de diodo se presenta como una opción válida para el tratamiento del cáncer de laringe en estadios iniciales.

Introduction: among the different therapeutic modalities for squamous carcinoma of the larynx in early stages, transoral laser surgery (CTL) is the treatment of choice. Materials and methods: CO2 laser is universally accepted as the best therapeutic tool in this regard. In situations of not being able to access that technology, it is possible to use other CTL resection instruments (radiofrequency, electro-scalpel). Among these, our work team has implemented the use of 1470 nm diode laser. In the present work we describe the preliminary results in the treatment of early stages of squamous carcinoma of the larynx with CTL using 1470 nm diode laser in elderly patients performed between January 2012 and December 2015 at the Otorhinolaryngology Service of Dr. Hospital C. Milstein. Results: Thirty-two patients with laryngeal cancer were treated, including 21, all over 65 years old, with squamous carcinoma of the Tis T1 and T2 larynx without cervical or metastatic involvement and without prior cancer treatment. Of the 21 patients included, 19 were given a single intervention and two were retreated with the same techniqu Conclusions: The use of laser 1470 nm diode for the treatment of squamous carcinoma of the larynx in early stages has allowed the control of the disease in the 21 patients operated with this technology, in an average follow-up time of 21 months. The CTL with diode laser is presented as a valid option for the treatment of laryngeal cancer in initial stages.

Introdução: entre os vários tratamentos para o carcinoma de células escamosas da laringe em modalidades estágios iniciais, laser cirurgia transoral (CTL) é o tratamento de escolha. O laser de CO2 é universalmente aceito como a melhor ferramenta terapêutica a este respeito. Em situações de não ter acesso a essa tecnologia, é possível usar outros instrumentos para CTL ressecção (radiofreqüência, eletrocautério). Materiais e métodos: Entre estes, a nossa equipa implementou o uso de diodo laser 1470 nm. Neste artigo descrevemos os resultados preliminares no tratamento do carcinoma de células escamosas da laringe, com CTL estágios iniciais utilizando o laser de diodo 1470 nm em pacientes idosos realizadas entre Janeiro de 2012 e Dezembro de 2015, Otorrinolaringologia do Hospital Dr. C. Milstein. Resultados: 32 pacientes com câncer de laringe, das quais 21 foram incluídos, todos com mais de 65 anos com carcinoma epidermóide de laringe Tis T1 e T2 sem ou compromisso de cancro cervical metastático e sem tratamento foram tratados. Dos 21 pacientes incluídos, 19 pacientes foram submetidos a uma única intervenção e dois eram reintevenidos com a mesma técnica. Conclusão: O uso de 1.470 nm diodo laser para o tratamento de carcinoma de células escamosas da laringe em estágios iniciais ajudou a controlar a doença em 21 pacientes tratados com esta tecnologia, em um seguimento médio de 21 meses. CTL diodo laser é apresentado como uma opção válida para o tratamento de carcinoma da laringe, em fases iniciais.