Self-evaluation of personal needs by community-living young stroke survivors using an online English language questionnaire.

BACKGROUND: Identifying personal needs of young stroke survivors is crucial for their recovery. PURPOSE: Identify factors, burden, and significance of unmet needs of young community-living stroke survivors. MATERIALS AND METHODS: We used online advertising and word-of-mouth snowballing to recruit participants for an English language online questionnaire constructed for this purpose. Eligible participants aged 18-55 at time of stroke. Needs were classified into seven domains: Healthcare Experience, Impairments from Stroke, Everyday Activities, Work/Study, Finances, Relationships, and Social Participation. Random-effects logistic regression was used to determine the probability of unmet needs and X2 test to determine significance of distribution across domains. RESULTS: Out of 137 responses recorded: 32 did not meet inclusion criteria, 29 duplicates identified were discarded, and 76 eligible participants were analysed. Respondents were median 37 (IQR 32-47) years at time of stroke, and median 3 (1-5) years since stroke. Fifty-eight (76%) females. Modified Rankin Scale median score of 1 (1-3). Of 48 identified potential needs, 25 (IQR 19-30) were rated unmet. Twenty (IQR 15-25) considered of high significance. Unmet needs most frequently occurred in the domains: Impairments from Stroke, Finances, and Social Participation. CONCLUSIONS: There is high burden of unmet needs in community-living young stroke survivors which are spread disproportionately across the identified domains.IMPLICATIONS FOR REHABILITATIONIdentifying personal needs of young stroke survivors is crucial for their recovery.Impairments after Stroke, Finances, and Social Participation were often selected as being high burden unmet needs for community-living young people after stroke.Employing a post-stroke checklist to guide exploration of needs in young stroke may better capture which needs are unmet.

A Case of Doxycycline-induced Melanin in the Gingiva Tissue: Case Report.

BACKGROUND: Gingival pigmentation is a discoloration of the gingiva due to a variety of lesions and conditions associated with several endogenous and exogenous etiologic features. OBJECTIVE: The purpose of this study is to describe a report of gingival pigmentation in a patient who used doxycycline. CASE REPORT: A 21-year-old Caucasian female was under dermatological treatment and antibiotic therapy with doxycycline 100 mg (one time a day) for 90 days. She presented brown pigmentation at the gingival margin on the facial surfaces of the upper and lower anterior incisors and premolars. The patient was evaluated by immunohistochemical (S-100, Melan-A, and HMB-45) and histopathologic analyses, and clinical history. Blood levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were analyzed by UV/Vis spectroscopy. The adrenaline, noradrenaline, and dopamine in blood were analyzed by high-performance liquid chromatography (HPLC); dehidroepiandrosterone (DHEA) in serum by radioimmunoassay; and luteinizing hormone (LH) and 25-Hydroxyvitamin D by chemiluminescence. Hematoxylin-eosin stained sections revealed keratinocytes with pigment compatible with melanin. The Fontana-Masson staining was positive in melanophages and in some basal keratinocytes. S-100, Melan A and HMB-45 were confirmed as positive markers of melanocytic differentiation in gingival tissue. We observed a significant increase in malondialdehyde (p˂0.05) and a decrease in superoxide dismutase levels (p˂0.05). The dopamine value was found to be 15 pg/ml (reference value ≤ 10 pg/ml). CONCLUSION: The use of doxycycline is associated with an increase in oxidative stress and of dopamine with melanin pigments in the gingival tissue. This case report showed a cause-effect relationship between exposure to doxycycline and pigmentation of the marginal gingiva.

Do clinical guidelines guide clinical practice in stroke rehabilitation? An international survey of health professionals.

PURPOSE: To identify health professionals awareness of stroke rehabilitation guidelines, and factors perceived to influence guideline use internationally. METHODS: Online survey study. Open-ended responses were thematically analysed, guided by the Consolidated Framework for Implementation Research. RESULTS: Data from 833 respondents from 30 countries were included. Locally developed guidelines were available in 22 countries represented in the sample. Respondents from high-income countries were more aware of local guidelines compared with respondents from low- and middle-income countries.Local contextual factors such as management support and a culture of valuing evidence-based practice were reported to positively influence guideline use, whereas inadequate time and shortages of skilled staff inhibited the delivery of guideline-recommended care. Processes reported to improve guideline use included education, training, formation of workgroups, and audit-feedback cycles. Broader contextual factors included accountability (or lack thereof) of health professionals to deliver rehabilitation consistent with guideline recommendations. CONCLUSION: While many health professionals were aware of clinical guidelines, they identified multiple barriers to their implementation. Efforts should be made to raise awareness of local guidelines in low- and middle-income countries. More attention should be paid to addressing local contextual factors to improve guideline use internationally, going beyond traditional strategies focused on individual health professionals.IMPLICATIONS FOR REHABILITATIONSystems are required so people and organisations are held accountable to deliver evidence-based care in stroke rehabilitation.Locally developed stroke rehabilitation guidelines should be promoted to boost awareness of these guidelines in low- and middle-income countries.In all regions, strategies to influence or adapt to the local setting, are required to optimise guideline use.

Factors associated with paid employment 12 months after stroke in A Very Early Rehabilitation Trial (AVERT).

BACKGROUND: Returning to work is an important outcome for stroke survivors. OBJECTIVES: This sub-study of a randomised controlled trial aimed to provide characteristics of working-age stroke participants and identify factors associated with return to work at 12 months. METHODS: We used paid employment data collected as part of A Very Early Rehabilitation Trial (AVERT, n=2104), an international randomised controlled trial studying the effects of very early mobilisation after stroke at 56 acute stroke units across Australia, New Zealand, the United Kingdom, Malaysia and Singapore. For the present analysis, data for trial participants < 65 years old were included if they were working at the time of stroke and had complete 12-month return-to-work data. The primary outcome was 12-month return to paid work. Univariable and multivariable logistic regression analyses were conducted to determine the association of multiple factors with return to work. RESULTS: In total, 376 AVERT participants met the inclusion criteria for this sub-study. By 12 months, 221 (59%) participants had returned to work at a median of 38 hr per week. Similar rates were found across geographic regions. On univariable analysis, the odds of returning to paid employment were increased with younger age (OR per year 0.95, 95%CI 0.92-0.97), no previous diabetes (0.4, 0.24-0.67), lower stroke severity (OR per National Institutes of Health Stroke Scale point 0.82, 0.78-0.86), less 3-month depressive traits (Irritability Depression Anxiety [IDA] scale) (OR per IDA point 0.87, 0.80-0.93), less 3-month disability (modified Rankin Scale), and prior full-time work (2.04, 1.23-3.38). On multivariable analysis, return to work remained associated with younger age (OR 0.94, 95%CI 0.91-0.98), lower stroke severity (0.92, 0.86-0.99), prior full-time work (2.33, 1.24-4.40), and less 3-month disability. CONCLUSIONS: Return to work at 12 months after stroke was associated with young age, acute stroke severity, 3-month disability and full-time employment before stroke. Greater understanding of this topic could help in developing programs to support successful resumption of work post-stroke.

Effects of Aerobic Exercise on Serum Biomarkers of Neuroplasticity and Brain Repair in Stroke: A Systematic Review.

OBJECTIVE: To provide a novel overview of the literature and to summarize the evidence for the effects of aerobic exercise (AE) on serum biomarkers neuroplasticity and brain repair in survivors of stroke. DATA SOURCES: We conducted a systematic review and searched MEDLINE, Embase, and Cochrane CENTRAL using terms related to AE, neuroplasticity, brain repair, and stroke. STUDY SELECTION: Titles, abstracts, and selected full texts were screened by 2 independent reviewers against the following inclusion criteria: including adult survivors of stroke, completing an AE intervention working within the AE capacity, and measuring at least 1 blood biomarker outcome of interest. DATA EXTRACTION: Two independent reviewers extracted data and assessed risk of bias using Risk of Bias in Nonrandomized Studies-of Interventions and Cochrane's Risk of Bias 2 tools. DATA SYNTHESIS: Nine studies (n=215 participants) were included, reporting on the following outcomes: brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), cortisol, interleukin 6, and myeloperoxidase. A single bout of high-intensity interval training significantly increased BDNF, IGF-1, and VEGF levels, and a 40-45-minute, 24-session, continuous 8-week AE training program significantly increased BDNF levels. No significant difference in response to any other AE intervention was found in other serum biomarkers. CONCLUSIONS: AE can significantly increase BDNF, IGF-1, and VEGF across different AE protocols in survivors of stroke. However, more research is needed to determine the optimal exercise intensity and modalities, specifically in survivors of acute and subacute stroke, and how this may relate to functional outcomes.

Factors associated with time to independent walking recovery post-stroke.

BACKGROUND: Past studies have inconsistently identified factors associated with independent walking post-stroke. We investigated the relationship between pre-stroke factors and factors collected acutely after stroke and number of days to walking 50 m unassisted using data from A Very Early Rehabilitation Trial (AVERT). METHODS: The outcome was recovery of 50 m independent walking, tested from 24 hours to 3 months post-stroke. A set of a priori defined factors (participant demographics: age, sex, handedness; pre-stroke: hypertension, ischaemic heart disease, hypercholesterolaemia, diabetes mellitus, atrial fibrillation; stroke-related: stroke severity, stroke type, ischaemic stroke location, stroke hemisphere, thrombolysis) were investigated for association with independent walking using a cause-specific competing risk Cox proportional hazards model. Respective effect sizes are reported as cause-specific adjusted HR (caHR) adjusted for age, stroke severity and AVERT intervention. RESULTS: A total of 2100 participants (median age 73 years, National Institutes of Health Stroke Scale 7, <1% missing data) with stroke were included. The median time to walking 50 m unassisted was 6 days (IQR 2-63) and 75% achieved independent walking by 3 months. Adjusted Cox regression indicated that slower return to independent walking was associated with older age (caHR 0.651, 95% CI 0.569 to 0.746), diabetes (caHR 0.836, 95% CI 0.740 to 0.945), severe stroke (caHR 0.094, 95% CI 0.072 to 0.122), haemorrhagic stroke (caHR 0.790, 95% CI 0.675 to 0.925) and right hemisphere stroke (caHR 0.796, 95% CI 0.714 to 0.887). CONCLUSION: Our analysis provides robust evidence for important factors associated with independent walking recovery. These findings highlight the need for tailored mobilisation programmes that target subgroups, in particular people with haemorrhagic and severe stroke.

Occlusive Disease and Upright Activity in Acute Ischemic Stroke.

The impact of out-of-bed upright activity on outcomes in ischemic stroke patients with severe extra- and intracranial stenosis or occlusion is unknown. Using ultrasound findings from a cohort recruited to A Very Early Rehabilitation Trial (AVERT) which compared higher dose very early mobilisation (VEM) to usual care (UC), we aimed to explore the association between occlusive disease and 3-month outcomes and occlusive disease-by-mobilisation treatment interactions. Participants with ischemic stroke, with carotid and transcranial Doppler ultrasounds performed ≤1 week after admission, were included in this single centre substudy in Melbourne, Australia. Reports were retrospectively reviewed to determine the degree of stenosis or presence of occlusion in the relevant arterial territory. Stenosis ≥70% extracranial or ≥50% intracranial were classified as severe or occlusion. Overall, 19% (n = 36/191) had occlusive disease in the affected circulation. About 40% (n = 14/36) with occlusive disease and 51% (n = 79/155) without had a 3-month favourable outcome (mRS 0-2) (adjusted OR0.53, CI0.17-1.67). Fourteen percent (n = 5) with occlusive disease and 4% (n = 6) without died by 3 months (adjusted OR2.52, CI0.6-10.7). Fifty percent (n = 11/22) of UC (adjusted OR0.86, CI0.23-3.2) and 21% (n = 3/14) of VEM participants (adjusted OR0.16, CI0.01-2.7) with occlusive disease had a favourable outcome. Almost 30% (n = 4) VEM participants with occlusive disease died (adjusted OR3.99, CI0.69-22.9) compared to 5% (n = 1) UC participants with occlusive disease (adjusted OR0.45, CI0.02-8.6), however numbers were small. No stenosis-by-treatment interactions were found. High quality prospective studies are needed to help guide decision making about when patients with occlusive disease should commence upright activity in acute stroke.

Construction and validation of a sepsis simulation scenario: a methodological study. / Construção e validação de um cenário de simulação sobre sepse: estudo metodológico.

OBJECTIVE: To build, validate and test a high-fidelity clinical simulation scenario for sepsis management. METHOD: Methodological study developed in three phases: construction of a simulation scenario using the framework Model of Nursing Training Simulation and protocols established by the Latin-American Sepsis Institute, content validation by nine judges, and scenario testing by two nurses from a hospital institution. Data analysis was carried out through Content Validity Index, with values > 0.90 among the judges being considered satisfactory. RESULTS: The simulation scenario was observed to be appropriate and obtained an overall value > 0.90. However, some adjustments to the scenario and the test were performed concerning textual clarity, functionality, and the protocol's pertinence, following the judges' suggestions. CONCLUSION: The validated simulation scenario is expected to be a facilitator instrument for educators and professionals in the permanent/continued education nuclei of teaching and health institutions.

Cerebral haemodynamics with head position changes post-ischaemic stroke: A systematic review and meta-analysis.

The effects of upright postures on the cerebral circulation early post-ischaemic stroke are not fully understood. We conducted a systematic review and meta-analysis to investigate the effects of head positioning on cerebral haemodynamics assessed by imaging methods post-ischaemic stroke. Of the 21 studies included (n = 529), 15 used transcranial Doppler. Others used near-infrared, diffuse correlation spectroscopy and nuclear medicine modalities. Most tested head positions between 0° and 45°. Seventeen studies reported changes in CBF parameters (increase at lying-flat or decrease at more upright) in the ischaemic hemisphere with position change. However, great variability was found and risk of bias was high in many studies. Pooled data of two studies ≤24 h (n = 28) showed a mean increase in cerebral blood flow (CBF) velocity of 8.5 cm/s in the ischaemic middle cerebral artery (95%CI,-2.2-19.3) from 30° to 0°. The increase found ≤48 h (n = 50) was of 2.3 cm/s (95%CI,-4.6-9.2), while ≤7 days (n = 38) was of 8.4 cm/s (95%CI, 1.8-15). Few very early studies (≤2 days) tested head positions greater than 30° and were unable to provide information about the response of acute stroke patients to upright postures (sitting, standing). These postures are part of current clinical practice and knowledge on their effects on cerebral haemodynamics is required.

Construção e validação de um cenário de simulação sobre sepse: estudo metodológico / Construcción y validación de un escenario de simulación sobre la sepsis: estudio metodológico / Construction and validation of a sepsis simulation scenario: a methodological study

RESUMO Objetivo Construir, validar e testar um cenário de simulação clínica de alta fidelidade para o manejo da sepse. Método Estudo metodológico desenvolvido em três fases: construção do cenário de simulação utilizando o framework Modelo de Simulação de Ensino em Enfermagem e os protocolos instituídos pelo Instituto Latino Americano de Sepse; validação do conteúdo por nove juízes; e o teste do cenário por dois enfermeiros de uma instituição hospitalar. A análise dos dados se deu pelo Índice de Validade de Conteúdo, considerando-se adequado um valor > 0,90 entre os juízes. Resultados O cenário de simulação mostrou-se apropriado, obtendo valor geral > 0,90. No entanto, foram feitos alguns ajustes no cenário e no teste no que tange à clareza da redação, às funcionalidades e à pertinência de protocolos, conforme sugestão dos juízes. Conclusão Espera-se que o cenário de simulação validado seja um instrumento facilitador para docentes e profissionais de núcleos de educação permanente/continuada de instituições de ensino e saúde.

RESUMEN Objetivo Construir, validar y probar un escenario de simulación clínica de alta fidelidad para el manejo de la sepsis. Método Estudio metodológico desarrollado en tres fases: construcción del escenario de simulación utilizando el framework del Modelo de Simulación de Enseñanza de Enfermería y los protocolos instituidos por el Instituto Latinoamericano de Sepsis; validación del contenido por nueve jueces; y prueba del escenario por dos enfermeras de una institución hospitalaria. Los datos fueron analizados por el Índice de Validez de Contenido, considerando un valor > 0,90 entre los jueces. Resultados El escenario de la simulación fue apropiado, obteniendo un valor global > 0,90. Sin embargo, se hicieron algunos ajustes en el escenario y la prueba en cuanto a la claridad de la redacción, la funcionalidad y la pertinencia de los protocolos, como sugirieron los jueces. Conclusión Se espera que el escenario de simulación validado sea una herramienta facilitadora para los profesores y profesionales de los centros de educación permanente/continuada de las instituciones de educación y salud.

ABSTRACT Objective To build, validate and test a high-fidelity clinical simulation scenario for sepsis management. Method Methodological study developed in three phases: construction of a simulation scenario using the framework Model of Nursing Training Simulation and protocols established by the Latin-American Sepsis Institute, content validation by nine judges, and scenario testing by two nurses from a hospital institution. Data analysis was carried out through Content Validity Index, with values > 0.90 among the judges being considered satisfactory. Results The simulation scenario was observed to be appropriate and obtained an overall value > 0.90. However, some adjustments to the scenario and the test were performed concerning textual clarity, functionality, and the protocol's pertinence, following the judges' suggestions. Conclusion The validated simulation scenario is expected to be a facilitator instrument for educators and professionals in the permanent/continued education nuclei of teaching and health institutions.

Alteração de forma dentária com resina direta: relato de caso / Dental form change with direct resin: case report / Cambiode formadental con resina directa: Reporte de un caso

Introdução:A melhoria da qualidade dos materiaisrestauradores odontológicos, sobretudo dasresinascompostas,permitiu a resolução de diversos problemas estéticos de forma conservadora, rápida e satisfatória.Objetivo:Este trabalho objetivou relatar um caso clínico de alteração de forma dos dentes anteriores, solucionado com resina composta pela técnica direta.Descrição do Caso:A paciente apresentava incisivos laterais ovalados e restauração classe IV insatisfatória no incisivo central superior direito.Após exame clínico e seleção de cor, os dentes 12, 12, 21 e 22 foram reanatomizadoscom resina composta direta através da técnica estratificada, além da substituição da restauração classe IV.Para uma perfeita mimetização dos elementos dentários, foram utilizadas resinas translúcidas, opacas e de efeito opalescente, além de resinas para reproduzir as camadas de esmalte e dentina. Conclusões:Uma boa seleção do material e aplicação correta da técnica,permitemrestaurações imperceptíveis,com excelente nível de texturização, acabamento e polimento, devolvendo a harmonia do sorriso (AU).

ntroduction:Theimprovement of the quality of dental restorative materials, especially of composite resins, allowed the resolution of several aesthetic problems in a conservative, fast and satisfactory way.Objective:This study aimed to report a clinical case of alteration of the shape of the anterior teeth, solved with resin composed by the direct technique. Case Description:The patient had oval lateral incisors and an unsatisfactory class IV restoration on the upper right central incisor. After clinical examination and color selection, teeth 12, 12, 21 and 22 were reanatomized with direct composite resin using the stratified technique, in addition to replacing the class IV restoration. For perfect mimicry of dental elements, translucent, opaque and opalescent resins were used, in addition to resins to reproduce the enamel and dentin layers.Conclusions:A good selection of the material and correct application of the technique, allow imperceptible restorations, with an excellent level of texturing, finishing and polishing, returning the harmony of the smile (AU).

Introducción: La mejora de lacalidad de losmateriales de restauración dental, especialmente de las resinas compuestas, permitiólaresolución de varios problemas estéticos de forma conservadora, rápida y satisfactoria. Objetivo: Este estudio tuvo como objetivo informar un caso clínico de alteración de la forma de los dientes anteriores, resuelto con resina compuesta por latécnica directa.Descripcióndel caso: El paciente tenía incisivos laterales ovales y una restauración de clase IV insatisfactoria en el incisivo central superior derecho. Después del examen clínico y la selección del color, los dientes 12, 12, 21 y 22 sereanatomizaron con resina compuesta directa utilizando la técnica estratificada, además de reemplazar la restauración de clase IV. Para una perfecta imitación de los elementos dentales, se utilizaron resinas translúcidas, opacas y opalescentes, además de resinas para reproducir las capas de esmalte y dentina.Conclusiones: Una buena selección del material y la correcta aplicación de la técnica, permiten restauraciones imperceptibles, con un excelente nivel de texturizado, acabado y pulido, devolviendo la armonía de la sonrisa (AU).

Solução estética multidisciplinar em dentes anteriores: relato de caso / Multidisciplinary aesthetic solution in previous teeth: case report / Solución estética multidisciplinariaem dientes anteriores: caso clínico

ntrodução:Pacientes com dentes curtos e ameias abertas, relatam muita insatisfação com seusorriso.A gengivoplastia, quando bem indicada, permite oaumento no tamanho da coroa dentária de forma a reduzir a necessidade de aumento incisal com resina composta. A reanatomização com resinas compostas para fechamento de ameias e aumentosincisais representa uma alternativa conservadora, pois trata-se de uma técnicaadesiva diretaque pode ser realizada sem nenhum desgaste dentário. Além disso é uma técnica reversível preferível para pacientes jovens. Objetivo:Apresentar um relato de caso clínico de paciente do sexo masculino, 22 anos, insatisfeito com o tamanho, cor e a forma dos seus dentes anteriores. Descrição do Caso:Ao exame clínico foi observado coroa curta, escurecimento fisiológico, espaços interdentais e desalinhamento das bordas incisais. O plano de tratamento proposto foi encaminhar para a gengivoplastia, clareamento dental pela técnica associada e reanatomização estética dos dentes anteriores com resinacomposta diretaestratificada com diferentescamadas e cores, e posterior texturização superficialdurante as fases de acabamento e polimento finais. Conclusões:Com a gengivoplastiae asrestaurações, obtivemos dentes reanatomizados, reproduzindo naturalidadede forma, textura e cor. Com planejamento e técnica adequada, foi possível restabelecer o sorriso comproporções, forma e naturalidade satisfatórias (AU).

Introduction:Patients with short teeth and open battlements, report a lot of dissatisfaction with their smile. Gingivoplasty, when properly indicated, allows for an increase in the size of the dental crown in order to reduce the need for incisal augmentation with composite resin. Resuscitation with composite resins for the closure of niches and incisal increases represents a conservative alternative, as it is a direct adhesive technique that can be performed without any dental wear. Furthermore, it is a preferable reversible technique for young patients.Objective:To present a case report of a 22-year-old male patient, dissatisfied with the size, color and shape of his anterior teeth.Case Description:The clinical examination showed a short crown, physiological darkening, interdental spaces and misalignment of the incisal edges. The proposed treatment plan was to refer to gingivoplasty, tooth whitening by the associated technique and aesthetic reanatomization of the anterior teeth with stratified direct composite resin with different layers and colors, and later surface texturing during the final polishing and finishing phases. Conclusions:With gingivoplastyand restorations, we obtained reanatomized teeth, reproducing natural form, texture and color. With proper planning and technique, it was possible to restore the smile with satisfactory proportions, shape and naturalness (AU).

Introducción: Los pacientes com dientescortos y almenasabiertas, informanmuchainsatisfaccióncom susonrisa. La gingivoplastia, cuando está indicada adecuadamente, permite un aumento em eltamaño de la corona dental para reducirlanecesidad de aumento incisalcon resina compuesta. La rstauración con resinas compuestas para elcierre de nichos y aumentos incisales representa una alternativa conservadora, ya que es una técnica adesiva directa que se puede realizar sinningún tipo de desgaste dental. Además, es una técnica reversiblepreferible para pacientes jóvenes. Objetivo: Presentar un informe de caso de un paciente masculino de 22 años, insatisfechocom eltamaño, el color y la forma de sus dientes anteriores.Descripcióndel caso:El examen clínico mostró una corona corta, oscurecimiento fisiológico, espaciosinterdentales y desalineación de los bordes incisales. El plan de tratamento propuesto era referirse a lagingivoplastia, elblanqueamiento dental mediante la técnica asociada y lareanatización estética de losdientes anteriores con resina compuestadirecta estratificada con diferentes capas y colores, y luego texturizar lasuperficie durante las fases finales de pulido y acabado. Conclusiones: Com lagingivoplasty yrestauracióndental, obtuvimosdientesreanatomizados, reproduciendo forma, textura y color naturales. Con una planificación y técnica adecuadas, fueposible restaurar lasonrisacon proporciones, forma y naturalidade satisfactorias (AU).

Evidences of HEV genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (Macaca fascicularis).

Hepatitis E virus genotype 3 (HEV-3) is an emerging zoonotic pathogen, responsible for sporadic cases of acute hepatitis E worldwide. Primate models have proven to be an essential tool for the study of HEV pathogenesis. Here we describe the outcomes of HEV infection in Macaca fascicularis (cynomolgus) inoculated experimentally with genotype 3. Eight adult cynomolgus macaques were inoculated intravenously with HEV-3 viral particles isolated from swine and human samples. Liver, spleen, duodenum, gallbladder and bile were sequential assessed up to the end-point of this study, 67 days post-inoculation (dpi). Our previously published findings showed that biochemical parameters return gradually to baseline levels at 55 dpi, whereas anti-HEV IgM and HEV RNA become undetectable in the serum and feces of all animals, indicating a non-viremic phase of recovery. Nevertheless, at a later stage during convalescence (67 dpi), the presence of HEV-3 RNA and antigen persist in central organs, even after peripheral viral clearance. Our results show that two cynomolgus inoculated with swine HEV-3 (animals I3 and O1) presented persistence of HEV RNA low titers in liver, gallbladder and bile. At this same stage of infection, HEV antigen (HEV Ag) could be detected in all infected animals, predominantly in non-reactive Kupffer cells (CD68+iNOS-) and sinusoidal lining cells. Simultaneously, CD4+, CD3+CD4+, and CD3+CD8+ immune cells were identified in hepatic sinusoids and small inflammatory clusters of lobular mononuclear cells, at the end-point of this study. Inability of HEV clearance in humans can result in chronic hepatitis, liver cirrhosis, with subsequent liver failure requiring transplantation. The results of our study support the persistence of HEV-3 during convalescence at 67 dpi, with active immune response in NHP. We alert to the inherent risk of viral transmission through liver transplantation, even in the absence of clinical and biochemical signs of acute infection. Thus, besides checking conventional serological markers of HEV infection, we strongly recommend HEV-3 RNA and antigen detection in liver explants as public health measure to prevent donor-recipient transmission and spread of hepatitis E.

Genetic Predisposition to Hepatocarcinogenesis in Inbred and Outbred Mouse Lines Selected for High or Low Inflammatory Response.

AIRmax and AIRmin mouse strains phenotypically selected for high and low acute inflammatory responsiveness (AIR) are, respectively, susceptible or resistant to developing hepatocellular carcinoma (HCC) induced by the chemical carcinogens urethane and diethylnitrosamine (DEN). Early production of TNF-α, IL-1ß, and IL-6 in the liver after DEN treatment correlated with tumor development in AIRmax mice. Transcriptome analysis of livers from untreated AIRmax and AIRmin mice showed specific gene expression profiles in each line, which might play a role in their differential susceptibility to HCC. Linkage analysis with SNP markers in F2 (AIRmax×AIRmin) intercross mice revealed two quantitative trait loci (QTL) in chromosomes 2 and 9, which are significantly associated with the number and progression of urethane-induced liver tumors. An independent linkage analysis with an intercross population from A/J and C57BL/6J inbred mice mapped regions in chromosomes 1 and 7 associated with the progression of urethane-induced liver tumors, evidencing the heterogeneity of HCC genetic control.

Gestalt-terapia: um método de trabalho para o processo saúde-doença em oncologia / Gestalt-terapy: a method of work for the health-disease process in oncology / Gestalt-therapy: un método de trabajo para el proceso de salud-enfermedad en oncología

A Gestalt-terapia é proposta como um método de trabalho para atendimentos, intervenções, acompanhamentos psicológicos e psicoterapia no tratamento oncológico. Por olhar o ser humano em sua totalidade, essa abordagem proporciona a abertura de consciência aos indivíduos para que não se percebam somente como pessoas adoecidas e entendam as implicações causadas por essa experiência, desenvolvendo ajustamentos criativos e ampliando o contato consigo, com o mundo e com o próprio adoecer. O processo saúde-doença é concebido nesse artigo como um processo complexo, pensa-se sobre a importância da atuação do psicólogo ao longo de todo o caminho para a saúde, como agente que media a relação do sujeito com o adoecimento, partindo dos paradigmas da Psicologia da Saúde, Psicologia Hospitalar e Psico-oncologia.

Gestalt-therapy is propose as a method of psychological treatment, interventions, counselling and psychotherapy in cancer treatment. By looking at the human being as a totality, this approach provides the opening of conscience to individuals so that they do not see themselves only like sick persons and understand the implications caused by this experience, developing creative adjustments and expanding contact with themselves, with the world and with their own sickness. The health-disease process is considered in this article as a complex process. It reflects upon the importance of the psychologist in all the way to health, as an agent that mediates the individual relationship with the illness, based on the paradigms of Health Psychology and Oncology Psychology.

La Gestalt-terapia se propone como un método de trabajo para la atención, intervenciones, acompañamientos psicológicos y psicoterapia en el tratamiento del cáncer. Al observar el ser humano en su totalidad, este enfoque proporciona abertura de conciencia a las personas para que no se consideren sólo como personas enfermas y entiendan las consecuencias causadas por esta experiencia, el desarrollo de ajustes creativos y aumentando el contacto con si mismo, con el mundo y con los enfermos a sí mismo. El proceso de salud-enfermedad está diseñado en este artículo como un proceso complejo, se piensa acerca de la importancia del psicólogo a lo largo de todo el camino a la salud, como un agente que media en la relación del sujeto con la enfermedad, a partir de los paradigmas de Psicología de la Salud y la Psicogía Oncológica.

Genotype-phenotype correlations and BH4 estimated responsiveness in patients with phenylketonuria from Rio de Janeiro, Southeast Brazil.

BACKGROUND: Genetic heterogeneity and compound heterozygosis give rise to a continuous spectrum of phenylalanine hydroxylase deficiency and metabolic phenotypes in phenylketonuria (PKU). The most used parameters for evaluating phenotype in PKU are pretreatment phenylalanine (Phe) levels, tolerance for dietary Phe, and Phe overloading test. Phenotype can vary from a "classic" (severe) form to mild hyperphenylalaninemia, which does not require dietary treatment. A subset of patients is responsive to treatment by the cofactor tetrahydrobiopterin (BH4 ). Genotypes of PKU patients from Rio de Janeiro, Brazil, were compared to predicted and observed phenotypes. Genotype-based estimations of responsiveness to BH4 were also conducted. METHODS: Phenotype was defined by pretreatment Phe levels. A standard prediction system based on arbitrary assigned values was employed to measure genotype-phenotype concordance. Patients were also estimated as BH4 -responders according to the responsiveness previously reported for their mutations and genotypes. RESULTS: A 48.3% concordance rate between genotype-predicted and observed phenotypes was found. When the predicted phenotypes included those reported at the BIOPKU database, the concordance rate reached 77%. A total of 18 genotypes from 30 patients (29.4%) were estimated as of potential or probable BH4 responsiveness. Inconsistencies were observed in genotypic combinations including the common "moderate" mutations p.R261Q, p.V388M, and p.I65T and the mild mutations p.L48S, p.R68S, and p.L249F. CONCLUSION: The high discordance rate between genotype-predicted and observed metabolic phenotypes in this study seems to be due partially to the high frequency of the so-called "moderate" common mutations, p.R261Q, p.V388M, and p.I65T, which are reported to be associated to erratic or more severe than expected metabolic phenotypes. Although our results of BH4 estimated responsiveness must be regarded as tentative, it should be emphasized that genotyping and genotype-phenotype association studies are important in selecting patients to be offered a BH4 overload test, especially in low-resource settings like Brazil.

Genetic predisposition to hepatocarcinogenesis in inbred and outbred mouse lines selected for high or low inflammatory response

AIRmax and AIRmin mouse strains phenotypically selected for high and low acute inflammatory responsiveness (AIR) are, respectively, susceptible or resistant to developing hepatocellular carcinoma (HCC) induced by the chemical carcinogens urethane and diethylnitrosamine (DEN). Early production of TNF-a, IL-1ß, and IL-6 in the liver after DEN treatment correlated with tumor development in AIRmax mice. Transcriptome analysis of livers from untreated AIRmax and AIRmin mice showed specific gene expression profiles in each line, which might play a role in their differential susceptibility to HCC. Linkage analysis with SNP markers in F2 (AIRmax×AIRmin) intercross mice revealed two quantitative trait loci (QTL) in chromosomes 2 and 9, which are significantly associated with the number and progression of urethane-induced liver tumors. An independent linkage analysis with an intercross population from A/J and C57BL/6J inbred mice mapped regions in chromosomes 1 and 7 associated with the progression of urethane-induced liver tumors, evidencing the heterogeneity of HCC genetic control.

Genetic predisposition to hepatocarcinogenesis in inbred and outbred mouse lines selected for high or low inflammatory response

AIRmax and AIRmin mouse strains phenotypically selected for high and low acute inflammatory responsiveness (AIR) are, respectively, susceptible or resistant to developing hepatocellular carcinoma (HCC) induced by the chemical carcinogens urethane and diethylnitrosamine (DEN). Early production of TNF-a, IL-1ß, and IL-6 in the liver after DEN treatment correlated with tumor development in AIRmax mice. Transcriptome analysis of livers from untreated AIRmax and AIRmin mice showed specific gene expression profiles in each line, which might play a role in their differential susceptibility to HCC. Linkage analysis with SNP markers in F2 (AIRmax×AIRmin) intercross mice revealed two quantitative trait loci (QTL) in chromosomes 2 and 9, which are significantly associated with the number and progression of urethane-induced liver tumors. An independent linkage analysis with an intercross population from A/J and C57BL/6J inbred mice mapped regions in chromosomes 1 and 7 associated with the progression of urethane-induced liver tumors, evidencing the heterogeneity of HCC genetic control.

Análise de sistemas reciprocantes quanto a produção de desvios e remoção de material obturador em canais radiculares: estudo in vitro / Analysis of reciprocal systems regarding the production of deviations and removal of filling material in root canals: in vitro study

O retratamento endodôntico é um procedimento realizado quando o tratamento anterior tem insucesso e visa reverter os processos infecciosos, removendo completamente o material obturador permitindo uma nova limpeza, modelagem e reobturação dos canais radiculares. Com vistas a melhoria das taxas de sucesso e eficiência do retratamento, vários sistemas de níquel-titânio (NiTi) têm sido desenvolvidos com a utilização de apenas um instrumento por meio de um movimento reciprocante, levantado novas perspectivas para o preparo biomecânico do canal radicular, bem como, o retratamento. Portanto, este estudo teve por objetivo analisar a produção de desvio e capacidade de limpeza durante retratamento dos canais mesiais de molares inferiores com curvaturas severas (30° e 70°), obturados com BioC Sealer após utilização dos sistemas reciprocantes. Uma amostra de sessenta molares inferiores foi dividida em quatro grupos experimentais, assim distribuídos: G1- X1-Blue (25.06); G2- WaveOne Gold Primary (25.07); G3- Reciproc Blue (25.08); G4- WA1 (25.07). Cada grupo continha 15 molares, totalizando 120 canais mesiais, os quais passaram pela aquisição e processamento das imagens iniciais no Microtomográfo, para que posteriormente, fosse realizado o pareamento dos grupos. Todos os grupos foram instrumentados com o sistema de rotação continua Pro Taper Next. Após instrumentação, foram obturados com cone de guta percha ProTaper Universal, selados e colocados em estufa a 37 °C, 100% de umidade durante 72 horas. Para análise de desvio e remoção da obturação dos canais as amostras foram escaneadas por meio da Microtomografia (MicroCT). Por fim, foi avaliado e medido o desvio apical através da comparação das imagens dos canais obtidas pelas Micro-CT após o retratamento, bem como a remoção do material obturador, para posterior análise estatística. Os resultados quanto a produção de desvio após remoção do material obturador, entre grupos, demonstrou não haver diferença estatisticamente significante tanto para os canais radiculares mesio vestibulares como para os canais mesio linguais (p > 0,05). Na análise intra grupo, não houve diferença em relação aos grupos G1(X1 Blue), G2 (Wave one Gold) e G3 (Reciproc Blue) (p > 0,05), porém o grupo G4 (WA1) apresentou diferença significante, mostrando maior grau de desvio no canal mesio lingual do que no mesio vestibular (p < 0,05). Com relação a remoção do material obturado, na análise entre grupo, para o canal Mesio vestibular, pode-se observar que em todos os grupos houve uma diminuição no sentido cervical para apical, porém, no grupo G4 (WA1) observou-se uma maior remoção tanto no terço médio quanto no apical. No terço cervical a maior remoção do material obturador ocorreu no grupo G2 (Wave one Gold), seguido do G4 (WA1), G3 (Reciproc Blue) e G1(X1 Blue). Para o canal mesio lingual, o grupo G4 (WA1) demonstrou uma maior estabilidade de remoção do material obturador em todos os terços. No terço cervical houve uma maior remoção do material obturador no grupo G2, seguido do G4, G3 e G1, já no terço médio foi no grupo G2, seguido do G1, G4 e G3. No terço apical, o grupo G4 promoveu maior capacidade de remoção de material obturador, seguido de G1, G2 e G3. Para comparação entre médias intragrupos, não houve diferença estatisticamente significante quando se comparou os terços cervical/médio para os Grupos G1 e G4 (tanto no canal Mesio vestibular como no mesio lingual) e terços médio/apical (apenas no canal Mesio lingual), porém, o terço apical foi observado uma maior dificuldade na remoção do material obturador. Conclui-se que a maiorias dos sistemas reciprocantes testados no retratamento promoveram desvio apical, porém o sistema WA1 foi capaz de produzir menos desvio no canal Mesio vestibular. Os sistemas reciprocantes utilizados foram capazes de remove grande parte do material obturador, mas não em sua totalidade, o terço apical foi o que mais dificultou a remoção do material obturador, porém, o sistema WA1 foi o que apresentou maior desempenho neste terço (AU).

Endodontic retreatment is a procedure performed when the previous treatment is unsuccessful and aims to reverse infectious processes, completely removing the shutter material allowing a new cleaning, modeling and reobturation of root canals. With a view to improving success rates and retreatment efficiency, several nickel-titanium (NiTi) systems have been developed with the use of only one instrument through a reciprocal movement, raising new perspectives for biomechanical preparation of the root canal, as well as retreatment. Therefore, this study aimed to analyze the production of deviation and cleaning capacity during retreatment of the mesiaal channels of lower molars with severe curvatures (30° and 70°), obtained with BioC Sealer after using reciprocating systems. A sample of sixty lower molars was divided into four experimental groups, thus distributed: G1- X1-Blue (25.06); G2- WaveOne Gold Primary (25.07); G3- Reciproc Blue (25.08); G4- WA1 (25.07). Each group contained 15 molars, totaling 120 mesiaal channels, which passed through the acquisition and processing of the initial images in the Microtomográfo, so that later, the pairing of the groups was performed. All groups have been instrumented with the continuous Rotation System Pro Taper Next. After instrumentation, they were filled with protaper universal percha gutcone, sealed and placed in a greenhouse at 37 °C, 100% humidity for 72 hours. For analysis of deviation and removal of the filling of the channels, the samples were scanned by microtomography (Micro-CT). Finally, apical deviation was evaluated and measured by comparing the images of the channels obtained by micro-CT after retreatment, as well as removal of the shutter material, for further statistical analysis. The results regarding the production of deviation after removal of the shutter material between groups, showed no statistically significant difference both for vestibular mesium root canals and for lingual mesio channels (p > 0.05). In the intra-group analysis, there was no difference in relation to groups G1(X1 Blue), G2 (Wave one Gold) and G3 (Reciproc Blue) (p > 0.05), but group G4 (WA1) showed a significant difference, showing a higher degree of deviation in the lingual mesium channel than in the vestibular mesium (p < 0.05). Regarding the removal of the obtained material, in the analysis between group, for the vestibular Mesio canal, it can be observed that in all groups there was a decrease in the cervical direction to apical, however, in group G4 (WA1) there was a greater removal in both the middle and apical third. In the cervical third the highest removal of the shutter material occurred in group G2 (Wave one Gold), followed by G4 (WA1), G3 (Reciproc Blue) and G1 (X1 Blue). For the lingual mesio channel, group G4 (WA1) demonstrated greater shutter material removal stability across all thirds. In the cervical third, there was a higher removal of the shutter material in group G2, followed by G4, G3 and G1, already in the middle third it was in group G2, followed by G1, G4 and G3. In the apical third, group G4 promoted higher shutter material removal capacity, followed by G1, G2 and G3. For comparison between intragroup means, there was no statistically significant difference when comparing the cervical/middle thirds for Groups G1 and G4 (both in the vestibular mesio channel and in the lingual mesium) and middle/apical thirds (only in the lingual Mesio canal), however, the apical third was observed a greater difficulty in removing the shutter material. It was concluded that most of the reciprocal systems tested in the retreatment promoted apical deviation, but the WA1 system was able to produce less deviation in the vestibular Mesio canal. The reciprocal systems used were able to remove much of the shutter material, but not in its entirety, the apical third was the one that most difficult to remove the shutter material, however, the WA1 system was the one that performed higher in this third (AU).