Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

Neurotrophic receptor kinase (NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors, and tropomyosin receptor kinase (TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these fusions. Currently, two generations TRK inhibitors have been developed. The representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target mutations. However, xDFG (TRKAG667C/A/S, homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib, and overcoming these resistances represents a major unmet clinical need. In this review, we summarize the acquired resistance mechanism of the first- and second-generation TRK inhibitors, and firstly put forward the emerging selective type II TRK inhibitors to overcome xDFG mutations mediated resistance. Additionally, we concluded our perspectives on new challenges and future directions in this field.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Calidad de vida en pacientes con enfermedad de Pompe: estudio observacional / Quality of Life in Patients with Pompe Disease: Cross-Sectional Study

Introducción: La enfermedad de Pompe es una enfermedad genética multisistémica y rápidamente progresiva, que causa compromiso muscular (esquelético, cardíaco y liso), severa hipotonía y dificultad en la deglución. Debido a la naturaleza de la enfermedad, la calidad de vida de las personas que la padecen puede verse más afectada con respecto a la población general. Método: Se llevó a cabo un estudio descriptivo de corte transversal. Se diseñó un instrumento tipo encuesta con preguntas de caracterización sociodemográfica y referentes a la enfermedad. Para medir la calidad de vida se aplicó el Medical Outcomes Study 36-Item Short Form (SF-36) Questionnaire. Se hizo una comparación entre grupos, con nivel de significancia de 0,05. Resultados: Se obtuvieron encuestas de 27 pacientes de seis países. La edad media fue de 40,52 años, el 59 % fueron mujeres, el 51 % casados, el 63 % activos laboralmente, con edad media de diagnóstico de 30,3 años (SD = 15,557). La dimensión con menor media fue el rol físico (10,2; IC 95 % = 1,5-21,9), mientras que la de mayor media fue la salud mental (65,5; IC 95 % = 56,9-74,0). El 29,7 % (IC 95 % = 11,2-48,0) de los encuestados consideró sentirse en peores condiciones de salud que el año anterior. Discusión: Se evidencia una baja calidad de vida en pacientes con EP, en comparación con la población general, si se tienen en cuenta otros estudios que utilizan el mismo cuestionario. Conclusiones: Se evidencia una baja calidad de vida en los pacientes con enfermedad de Pompe participantes; las dimensiones asociadas con parámetros físicos fueron las de menores puntuaciones.

Introduction: Pompe disease is a rapidly progressive, multisystemic genetic disease that causes muscle involvement (skeletal, cardiac and smooth), severe hypotonia and difficulty in swallowing. Due to the nature of the disease, the quality of life may be more affected compared to the general population. Method: A descriptive cross-sectional study was carried out. A survey-type instrument was designed with questions of sociodemographic characterization and those referring to the disease. To measure Quality of Life, the Medical Outcomes Study 36-Item Short Form (SF-36) questionnaire was applied. A comparison was made between groups with a significance level of 0,05. Results: 27 surveys of patients from six countries were obtained. The mean age 40.52 years, women 59 %, married 51 %, 63 % active in employment, with a mean age of diagnosis of 30.3 years (SD = 15,557). The dimension with the lowest mean was the Physical Role (10.2; 95 % CI = 1.5 - 21.9), while the one with the highest mean was the Mental Health dimension (65.5; 95 % CI = 56.9 - 74.0). 29.7 % (95 % CI = 11.2 - 48.0) of those surveyed considered they felt in worse health conditions than the previous year. Discussion: Low quality of life is evidenced in patients with PD in comparison to the general population described in other studies using the same questionnaire. Conclusions: A low quality of life is evidenced in the study individuals where the dimensions related to the physical area were lower.

Factores relacionados con la adherencia al tratamiento de rehabilitación de los pacientes con Diabetes Mellitus tipo 2 con amputación de miembro inferior

Objetivo: Determinar los factores clínicos y sociodemográficos relacionados con la adherencia al tratamiento de rehabilitación de los pacientes con Diabetes Mellitus tipo 2 con amputación de miembro inferior. Material y métodos: Estudio observacional, retrospectivo, comparativo y relacional; se incluyeron 113 pacientes con DM tipo 2 del Departamento de Investigación, Docencia y Rehabilitación Integral en Amputados, quemados y Trastornos Posturales del Instituto Nacional de Rehabilitación "Dra. Adriana Rebaza Flores" AMISTAD PERÚ - JAPÓN, que ingresaron en el periodo 2016 al 2019. Se recolectaron variables sociodemográficas y clínicas; y para la adherencia al tratamiento de rehabilitación se consideró la asistencia de los pacientes a 5 áreas de atención en salud, y el alta de prótesis de los pacientes. Resultados: El 75,52 % de pacientes fueron del sexo masculino, con edad media de 66,6 ± 12,1; y la media del tiempo de alta de prótesis fue 11,4 ± 6,75 meses. Se encontró diferencia significativa entre adherencia y no adherencia en la edad, nivel socioeconómico, estado civil y cobertura de atención (p < 0,05) Conclusiones: La mayoría de los pacientes amputados con DM tipo 2 fueron del sexo masculino cuyo cumplimiento o adherencia a la rehabilitación se relacionó con factores sociodemográficos como la edad, estado civil, nivel socioeconómico y cobertura de salud.

SUMMARY Objective: To determine clinical and sociodemographic factors related to the adherence to rehabilitation treatment among type 2 diabetic patients who underwent lower limb amputation. Methods: An observational retrospective study that included 113 type 2 diabetic patients attended at the Departamento de Investigación, Docencia y Rehabilitación Integral en Amputados, quemados y Trastornos Posturales del Instituto Nacional de Rehabilitación "Dra. Adriana Rebaza Flores" AMISTAD PERÚ - JAPÓN from 2016 to 2019. Clinical and sociodemographic variables were collected; to measure adherence patients had to attend five evaluations and the discharge visit after a prosthetic device had been inserted. Results: 75.52% were males; mean age was 66.6 ± 12.1 years, and mean time after insertion of the prosthetic device was 11.4 ± 6.75 months. Factors associated with no adherence were age, socioeconomic level, marital status and health care coverage (p<0.05). Conclusions: Most of the type 2 diabetic patients who underwent lower limb amputation were males, adherence to the rehabilitation treatment was related to sociodemographic factors.

Efectos del entrenamiento de la fuerza en personas con diabetes mellitus tipo II: revisión sistemática / Effects of resistance training in people with Type II diabetes mellitus: systematic review / Efeitos do treinamento de resistência em pessoas com diabetes mellitus tipo II. revisão sistemática

El presente artículo busca analizar las evidencias aportadas del entrenamiento de la fuerza comprobando su influencia en la Diabetes Mellitus tipo II utilizando la literatura existente sobre este objeto de estudio. Se realizo una revisión sistemática siguiendo las directrices PRISMA donde el principal contexto fue el entrenamiento de la fuerza en pacientes con Mellitus II, siendo buscados en bases de datos Pubmed, Embase y Scopus donde fueron seleccionados 7 artículos. Los hallazgos señalan consistentemente que el entrenamiento de la fuerza bien programado incide gradualmente en algunos marcadores que identifican la diabetes Mellitus II al realizar intervenciones con sistemas de entrenamiento de la fuerza de forma positiva. Los autores recomiendan estudios con muestras mayores en lo posible de tipo control para verificar la incidencia del entrenamiento en las variables mencionadas en este estudio.

This Article Seeks analyzes the evidence provided by strength training, verifying its influence on Type II Diabetes Mellitus by using the existing literature on this subject of study. A systematic review was carried out following the PRISMA guidelines, where the main context was strength training in patients with Mellitus II. The search was carried out in Pubmed, Embase, and Scopus databases where 7 articles were selected. The findings consistently indicated that a well-structured strength training program gradually affected some markers that identify diabetes Mellitus II when performing interventions with strength training systems in a positive way. The authors recommend control-type studies with larger samples, if possible, to verify the incidence of training in the variables mentioned in this study.

Este artigo procura analisar as evidências fornecidas pelo treinamento de força, verificando sua influência no Diabetes Mellitus tipo II utilizando a literatura existente sobre este objeto de estudo. Foi realizada uma revisão sistemática seguindo as diretrizes PRISMA onde o principal contexto foi o treinamento de força em pacientes com Mellitus II, sendo pesquisada nas bases de dados Pubmed, Embase e Scopus onde foram selecionados 7 artigos. Os achados indicam consistentemente que o treinamento de força bem programado afeta gradualmente alguns marcadores que identificam o diabetes Mellitus II ao realizar intervenções com sistemas de treinamento de força de forma positiva. Os autores recomendam estudos do tipo controle com amostras maiores, se possível, para verificar a incidência de treinamento nas variáveis mencionadas neste estudo.

Rehabilitación en la enfermedad de Pompe / Pompe disease rehabilitation management

Introducción: Gracias a la nueva herramienta de tratamiento con la terapia de reemplazo enzimático en la enfermedad de Pompe, se ha reducido la mortalidad a corto plazo. Contenidos: Esta herramienta permite a los pacientes mantener la independencia funcional y la adaptación de las habilidades motrices para su participación en varios aspectos de la vida diaria. Conclusiones: El abordaje de estos pacientes debe ser multidisciplinario, para dar un manejo integral a la condición clínica de cada individuo, y procurar el tratamiento de los sistemas físicos y emocionales que se pueden ver alterados con el curso de la enfermedad: osteomuscular, cardiovascular y respiratorio, deglución, lenguaje, nutrición y psicológico, incluidos los cuidados paliativos y el manejo del dolor.

Introduction: Enzyme replacement therapy in Pompe disease reduces short-term mortality. Contents: This therapy allows patients to maintain functional independence and adaptation of motor skills for patient participation in various aspects of daily life. Conclusions: The approach with this patients should be multidisciplinary to provide comprehensive management of the clinical condition of each individual seeking treatment of the physical and emotional aspects that may be altered in the disease progression: musculoskeletal, cardiovascular, respiratory, swallowing, language, nutritional and psychological; also including palliative care and pain management.

Enfermedad de Pompe: historia, epidemiología, fisiopatología y manifestaciones clínicas / Pompe's disease: History, epidemiology, pathophysiology and clinical manifestations

Introducción: La enfermedad de Pompe o glucogenosis tipo II pertenece al grupo de las miopatías metabólicas y es producida por la deficiencia parcial o total de la enzima alfa glucosidasa ácida. La ausencia/ déficit de esta enzima genera un almacenamiento de glucógeno en el interior de los lisosomas en diversos tejidos, incluidos el músculo esquelético, el miocardio y las células del músculo liso. Se trata de una enfermedad multisistémica que puede tener un inicio temprano o tardío de los síntomas. Contenidos: En este artículo se describirán los aspectos históricos de la enfermedad, su fisiopatología y sus manifestaciones clínicas, con el énfasis puesto en su inicio temprano o tardío. Conclusiones: Es necesario reconocer la enfermedad de Pompe debido a que esta patología es susceptible de tratamiento.

Introduction: Pompe's disease or glucogenosis type II belongs to the group of metabolic myopathies and is caused by a partial or total deficiency of the acid alpha glucosidase enzyme. The lack/deficiency of this enzyme generates glycogen storage inside the lysosomes in various tissues including skeletal muscle, myocardium and smooth muscle cells. It is a multisystemic disease that can have an early onset or a late onset. Contents: In this article, the historical aspects, the pathophysiology and the clinical manifestations of the disease, will be described. Conclusions: It is necessary to recognize Pompe disease because this pathology is treatable.

Tratamiento de la enfermedad de Pompe / Treatment of Pompe Disease

Introducción: La enfermedad de Pompe es un trastorno de origen genético causado por la deficiencia de la enzima alfa-glucosidasa ácida, que se caracteriza por el acumulo anormal de glucógeno en los músculos y otros tejidos, generando una debilidad muscular progresiva, la cual debe ser diagnosticada y tratada de forma oportuna, ya que de esto dependerá el pronóstico, la sobrevida y la funcionalidad de los pacientes con esta condición. Contenidos: El abordaje multidisciplinario incluye tanto una adecuada valoración y soporte nutricional como el inicio del tratamiento modificador de enfermedad a través de la terapia de reemplazo enzimático, que a su vez dependerá de la forma de presentación, la variante genética, el perfil inicial del paciente, las condiciones especiales que puedan existir y las metas propias para cada paciente. Para garantizar un manejo adecuado, se deben realizar estudios de seguimiento con parámetros objetivos, evaluar posibles eventos secundarios e instaurar su manejo en caso de presentarlos. Conclusiones: El pronóstico de esta enfermedad dependerá del inicio oportuno del tratamiento, la implementación de pautas nutricionales adecuadas y el establecimiento del seguimiento de los parámetros clínicos y paraclínicos para cada uno de los pacientes.

Introduction: Pompe disease is a disorder of genetic origin caused by the deficiency of the acid alpha-glucosidase enzyme, which is characterized by the abnormal accumulation of glycogen in the muscles and other tissues, generating progressive muscle weakness, which must be diagnosed and treated in a timely manner, since the prognosis, survival, and functionality of patients with this condition will depend on this. Contents: The multidisciplinary approach includes both an adequate evaluation and nutritional support as well as the initiation of disease-modifying treatment through enzyme replacement therapy, which in turn will depend on the form of presentation, the genetic variant, the initial profile of the patient, the special conditions that may exist and the specific goals for each patient. To guarantee adequate management, follow-up studies must be carried out with objective parameters, evaluate possible secondary events and establish their management in case of presenting them. Conclusions: The prognosis of this disease will depend on the timely initiation of treatment, the implementation of adequate nutritional guidelines and the establishment of monitoring of clinical and paraclinical parameters for each of the patients.

Application of laparoscopic ultrasound in retroperitoneal radical nephrectomy for renal cell carcinoma with Type II inferior vena cava tumor thrombectomy

Background: The aim of this study was to investigate the application value of laparoscopic ultrasound (LU) in retroperitoneal radical nephrectomy for renal cell carcinoma with Type II inferior vena cava tumor thrombectomy (RRN-RCC-TII-IVCTT). Methods: The clinical data (operative time, length of tumor thrombus, tumor length, intraoperative bleeding, clinical stage, histological type, residual tumor tissue, and postoperative follow-up) of 6 patients who underwent LU-guided RRN-RCC-TII-IVCTT were retrospectively analyzed, and the intraoperative experience of LU was also summarized. Results: All 6 patients recovered well with liver and kidney functions returning to normal, and no tumor recurrence, metastasis, or vena cava tumor thrombus. Conclusions: LU-guided RRN-RCC-TII-IVCTT is a feasible treatment option, which locates the tumor accurately by retroperitoneal approach and provides the additional benefit of reduced intraoperative bleeding and shortened operative time, also achieving the much sought-after goal of precision.

Research progress on the role of type II innate lymphoid cells in liver diseases / 中华肝脏病杂志

Type II innate lymphoid cell (ILC2) is a newly identified innate immunological cell that belongs to the lymphocyte lineage in cell morphology, resides in the body's mucosal tissues, and has the dual functions of innate and adaptive immunity to promote tissue remodeling and repair after injury. Additionally, it is involved in the occurrence and development of a variety of liver diseases and plays an important role in maintaining the immunological homeostasis of the liver region. This article reviews the differentiation, development, and biological functions of ILC2, with particular attention to the research progress in liver diseases.

Leptin-mediated ERK Signaling Pathway Promotes the Transformation of Rat Alveolar Type II Epithelial Cells Induced by Yunnan Tin Mine Dust / 中国肺癌杂志

BACKGROUND@#Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust.@*METHODS@#Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method.@*RESULTS@#Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased.@*CONCLUSIONS@#Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.

Effect of Gualou Xiebai Decoction on type II cardiorenal syndrome based on endothelial/epithelial-to-mesenchymal transition and its mechanism / 中国药理学通报

Aim To investigate the protective effects of different doses Gualou Xiebai Decoction (GXD) on type II cardiorenal syndrome (type II CRS) and explore its preliminary mechanisms. Methods The type II cardiorenal syndrome rat model was replicated by li-gating the left anterior descending coronary artery. After 10 weeks of intragastric administration, the cardiac function of the rats in each group was evaluated by echocardiography; serum were collected for biochemical testing; heart and kidney tissue samples were stained with HE and Masson to observe pathological changes. The hydroxyproline content in the heart and kidney was detected. The expression levels of endothelial/epitheli-al-to-mesenchymal transition (EndMT/EMT) related proteins in heart and kidney tissues were detecterd by immunofluorescence double staining

Two Cases of Successful Treatment of Percutaneous Transarterial Embolization via Costocervical Trunk Approach for Patients with Persistent Type II Endoleak and Sac Enlargement of Arch Aneurysm after Thoracic Endovascular Aortic Repair (TEVAR) / 日本心臓血管外科学会雑誌

Among the less reported complications after thoracic endovascular aortic repair (TEVAR) is type II endoleak (T2EL). The intercostal and bronchial artery are known as feeder vessels to T2EL after TEVAR. We experienced two cases of successful treatment of percutaneous transarterial feeder vessels embolization via right costocervical trunk approach for patients with persistent T2EL and sac enlargement of an arch aneurysm after TEVAR. The costocervical trunk route is possible for key vessels to construct a collateral pathway to feeder vessels of the endoleak nidus of T2EL after TEVAR procedures for aortic arch aneurysm. A preembolizational Catheter-Directed CT angiogram (CTA) can be helpful to prevent harmful complications (e.g., spinal cord infarction).

A Retrospective Study of Mucopolysaccharidosis Type II in Brazil - Data from Brazilian Health System (DATASUS)

Abstract Data on Mucopolysaccharidosis type II (MPS II) in Latin America are scarce. This retrospective database study, using data from the Informatics Department of the Brazilian Health System (DATASUS), aimed to estimate the prevalence of MPSII in Brazil from 2008 to 2020 and to describe demographic and clinical profiles from patients under treatment. The study population was derived from DATASUS records of MPS II (ICD-10 E76.1) diagnosed in Brazil. Initially 455 patients were found, but only 181 patients who were receiving idursulfase treatment were included in this study. Among these cases, as expected in a X-linked disease, all were males and 40% of the cases were recorded in the Southeast region, and another 34% in the Northeast region. The biggest proportion of patients (39%) were diagnosed when they were 10-19 years old. There are 212 clinical conditions associated with MPS II, although the main comorbidities related to MPSII include: abdominal/inguinal hernia, respiratory complications, and carpal tunnel syndrome. Respiratory disorders were the fifth most frequent comorbidity recorded in these patients. The healthcare professionals in Brazil more involved in the diagnosis of MPS II were radiologists, followed by geneticists and cardiologists. Despite some limitations, DATASUS is a relevant database to provide information on rare diseases such as MPS II. Most cases were reported in southeast and northeast regions, respectively. This information is crucial to help design targeted public policies.

Construção e validação de painel móvel para educação em saúde de usuários com diabetes mellitus tipo II na atenção primária à saúde / Construction and validation of a mobile panel for health education of users with type II diabetes mellitus in primary health care

Resumo: Este estudo de produção tecnológica que teve como objetivo, construir, validar o conteúdo e aparência de uma tecnologia educacional, no formato de painel móvel, para educação em saúde de usuários com Diabetes Mellitus tipo II, atendidos na Atenção Primária à Saúde do município de Ji-Paraná - Rondônia. Método: trata-se de estudo metodológico, realizado em três fases: 1. Exploratória ­ quando foi realizado o diagnóstico situacional e busca na literatura sobre Diabetes Mellitus tipo II. 2. Desenvolvimento - definição, validação do conteúdo que compôs o painel móvel e elaboração gráfica e designer. 3. Validação: validação da aparência do painel móvel utilizando o Instrumento para Validação de Aparência de Tecnologias Educacionais em Saúde. Resultados: Participaram do diagnóstico situacional 17 profissionais da saúde, sendo 41,18% representada pela equipe de enfermagem. Os participantes afirmaram realizar educação em saúde para o autocuidado durante a realização das reuniões, atendimentos e/ou consultas dos usuários com DM tipo II. Dois (15,68%) participantes afirmaram que utilizavam alguma tecnologia educacional durante os atendimentos e/ou consultas e quatro (40%) participantes utilizavam alguma tecnologia educacional nas reuniões com usuários com diabetes Mellitus tipo II. O conteúdo do painel móvel foi organizado nos seguintes tópicos: Diabetes Mellitus tipo II: o que é? Quais as complicações da doença? O que é autocuidado? Cuidados com a alimentação, os pés, os olhos, a saúde bucal e mental; uso correto das medicações; práticas de exercícios físicos e cessação do tabagismo. O Índice de Validade de Conteúdo atingiu 94,44%, sendo considerado satisfatório. A aparência foi validada, obtendo Índice de Validade de Aparência total de 92%. O painel móvel foi confeccionado em acrílico, contendo frente e verso, com rodas para facilitar o manuseio e uso em diferentes locais. Conclusão: a tecnologia desenvolvida possui capacidade de cumprir o propósito de subsidiar a equipe de saúde na educação dos usuários com Diabetes Mellitus tipo II. O painel móvel apresenta qualidades de inovação, praticidade no uso e validade de conteúdo e aparência. Seu potencial para a interlocução entre a equipe de saúde e usuários visa a construção do conhecimento sobre a doença, autocuidado e prevenção de complicações. A replicabilidade da tecnologia em saúde cumpre o papel social deste estudo.

Abstract: This technological production study aimed to build, validate the content and appearance of an educational technology, in the form of a mobile panel, for health education of users with Type II Diabetes Mellitus, assisted in Primary Health Care in the municipality of Ji -Paraná - Rondônia. Method: this is a methodological study, carried out in three phases: 1. Exploratory ­ when the situational diagnosis and literature search on Type II Diabetes Mellitus were carried out. 2. Development - definition, validation of the content that made up the mobile panel and graphic design and design. 3. Validation: validation of the appearance of the mobile panel using the Instrument for Appearance Validation of Educational Technologies in Health. Results: 17 health professionals participated in the situational diagnosis, 41.18% of which were represented by the nursing team. The participants stated that they carried out health education for self-care during meetings, consultations and/or consultations with users with type II DM. Two (15.68%) participants stated that they used some educational technology during consultations and/or consultations and four (40%) participants used some educational technology in meetings with users with type II diabetes Mellitus. The content of the mobile panel was organized into the following topics: Type II Diabetes Mellitus: what is it? What are the complications of the disease? What is self-care? Care for food, feet, eyes, oral and mental health; correct use of medications; physical exercise practices and smoking cessation. The Content Validity Index reached 94.44%, being considered satisfactory. Appearance was validated, obtaining a total Appearance Validity Index of 92%. The mobile panel was made of acrylic, containing front and back, with wheels to facilitate handling and use in different places. Conclusion: the developed technology has the capacity to fulfill the purpose of supporting the health team in the education of users with Type II Diabetes Mellitus. The mobile panel presents qualities of innovation, practicality in use and validity of content and appearance. Its potential for dialogue between the health team and users is aimed at building knowledge about the disease, self-care and prevention of complications. The replicability of health technology fulfills the social role of this study.

Modelo predictivo de riesgo para el diagnóstico temprano de la diabetes mellitus de tipo 2 / Predictive model of risk for the early diagnosis of type II diabetes mellitus i: en

Introducción: El diagnóstico temprano de la diabetes mellitus de tipo 2 permite al personal de salud implementar estrategias para evitar las complicaciones crónicas que pudieran derivarse. A tales efectos, en las últimas dos décadas se han desarrollado modelos predictivos que incluyen cada día más variables. Objetivo: Elaborar un modelo predictivo para el diagnóstico temprano de la diabetes mellitus de tipo 2 en una población holguinera. Métodos: Se realizó un estudio de cohorte que incluyó a todos los pacientes atendidos en las consultas de endocrinología del área de salud Pedro Díaz Coello y del Hospital Militar Fermín Valdés Domínguez de la provincia de Holguín, para lo cual se tomaron 2 cohortes: una de análisis y otra de validación. Para el procesamiento estadístico se efectuó el análisis univariado y el multivariado; en tanto se determinó la asociación entre variables dependientes e independientes. Resultados: En la serie predominaron el sexo femenino, los pacientes sin antecedentes de diabetes mellitus e hipertensión arterial, así como los que presentaban hipotiroidismo, enfermedad periodontal y normopeso, entre otros; asimismo, el modelo resultó significativo estadísticamente (X2=31,1 y p=0,000) y explicó 80,9 % de la variable de salida, validada por las variables de análisis. La sensibilidad fue de 96,9 % y la especificidad de 86,6 %; mientras que el área bajo la curva tuvo un rango de 0,725 a 0,833. Conclusiones: El modelo predictivo elaborado es una herramienta muy útil para el diagnóstico de pacientes con riesgo de presentar diabetes mellitus de tipo 2.

Introduction: The early diagnosis of the type II diabetes mellitus allows the health staff to implement strategies in order to avoid the chronic complications that could be derived. To such effects, in the last two decades predictive models have been developed that include more variables every day. Objective: To elaborate a predictive model for the early diagnosis of type II diabetes mellitus in a population from Holguín. Methods: A cohort study was carried out that included all the patients assisted in the endocrinology services of Pedro Díaz Coello health area and Fermín Valdés Domínguez Military Hospital in Holguín province, for which 2 cohorts were taken: one of analysis and another of validation. For the statistical processing the univaried and multivaried analysis were carried out; as long as the association between dependent and independent variables was determined. Results: In the series there was a prevalence of the female sex, patients without history of diabetes mellitus and hypertension, as well as those that presented hypothyroidism, periodontal disease and normal weight, among others; also, the pattern was statistically significant (X2=31.1 and p=0.000) and explained 80.9 % of the logout variable validated by the analysis variables. The sensibility was of 96.9 % and the specificity of 86.6 %; while the area under the curve had a range from 0.725 to 0.833. Conclusions: The predictive model elaborated is a very useful tool for the diagnosis of patients with risk of type II diabetes mellitus.

Luschka and the carotid body / Luschka e o corpo carotídeo

The 'carotid body' is a small structure sited at the bifurcation of the common carotid artery. The macroscopic features of the carotid body, and items of the extrinsic nervous, and vascular supplies, were initially described by Taube (1743), complemented by a number of authors that followed, proceeding until Luschka (1962), who added the first microscopic study. The macroscopic features of the carotid body, including location, extrinsic innervation, and vascular supply, then provided, were described in a relatively satisfactory manner. However, despite Luschka's great and admirable effort, the microscopic findings seem to be flawed, what can be ascribed to the technical limitations at the time, and the artifacts due to the used procedures. Nevertheless, there is no doubt that Luschka and his forerunners provided an important step for forthcoming research on the carotid body, and its innervation.

O 'corpo carotídeo' é uma pequena estrutura situada na bifurcação da artéria carótida comum. Os aspectos macroscópicos do corpo carotídeo e itens sobre o suprimento nervoso e vascular extrínsecos foram descritos inicialmente por Taube (1743), complementados por um certo número de autores que seguiram, prosseguindo até Luschka (1962), que acrescentou o primeiro estudo microscópico. Os aspectos macroscópicos do corpo carotídeo, incluindo localização, inervação extrínseca e suprimento vascular, então providos, foram descritos de modo relativamente satisfatório. Entretanto, apesar do grande e admirável esforço de Luschka, os achados microscópicos aparecem falhos, o que pode ser atribuído às limitações técnicas daquele tempo e a artefatos devidos aos procedimentos utilizados. Todavia, não há dúvida que Luschka e seus precursores proveram um importante passo para pesquisas que vieram sobre o corpo carotídeo e da sua inervação.

Bloqueio do Quadrado Lombar Tipo II para Tratamento de Dor Oncológica de Difícil Controle ­ Relato de Caso / Type II Quadratus Lumborum Block for Treatment of Difficult-to-Control Cancer Pain - Case Report

A dor oncológica é um fator impactante para a qualidade de vida dos pacientes, cujo manejo é desafiador, pois pode ser refratária à terapia sistêmica multimodal otimizada. Descrito pela primeira vez em 2007, o bloqueio do quadrado lombar tem sido amplamente utilizado para promover analgesia em região abdominal.

Cancer pain is a factor that impacts the quality of life of patients, whose management is challenging because it can be refractory to optimized multimodal systemic therapy. First described in 2007, quadratus lumborum block has been widely used to promote analgesia in the abdominal region.

MUCOPOLYSACCHARIDOSIS TYPE 2: NARRATIVE REVIEW

Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare, progressive, multisystemic lysosomal storage disease caused by de?ciency of iduronate 2 sulfatase, an enzyme responsible for the degradation of the mucopolysaccharides dermatan (DS) and keratan sulfate (QS), causing their accumulation at the lysosomal level. It is an X-linked disease, therefore it is common to ?nd most cases in men, rarely in women, it is considered an orphan disease given an incidence of approximately 1/100,000 live births. Various phenotypes of severe (2/3) and attenuated disease have been described. The diagnosis is based on clinical ?ndings and the measurement of mucopolysaccharides DS and QS in urine, which are elevated, con?rmed by determining the enzyme de?ciency in serum, leukocytes and ?broblasts. It has been observed that in patients with enzyme replacement therapy somatic symptoms have decreased, however there are several studies of alternative therapies in the future, including gene therapy as an alternative in the future