Transcranial electrical stimulation modulates emotional experience and metabolites in the prefrontal cortex in a donation task.

Understanding the neural, metabolic, and psychological mechanisms underlying human altruism and decision-making is a complex and important topic both for science and society. Here, we investigated whether transcranial Direct Current Stimulation (tDCS) applied to two prefrontal cortex regions, the ventromedial prefrontal cortex (vmPFC, anode) and the right dorsolateral prefrontal cortex (DLPFC, cathode) can induce changes in self-reported emotions and to modulate local metabolite concentrations. We employed in vivo quantitative MR Spectroscopy in healthy adult participants and quantified changes in GABA and Glx (glutamate + glutamine) before and after five sessions of tDCS delivered at 2 mA for 20 min (active group) and 1 min (sham group) while participants were engaged in a charitable donation task. In the active group, we observed increased levels of GABA in vmPFC. Glx levels decreased in both prefrontal regions and self-reported happiness increased significantly over time in the active group. Self-reported guiltiness in both active and sham groups tended to decrease. The results indicate that self-reported happiness can be modulated, possibly due to changes in Glx concentrations following repeated stimulation. Therefore, local changes may induce remote changes in the reward network through interactions with other metabolites, previously thought to be unreachable with noninvasive stimulation techniques.

Cortical folding correlates to aging and Alzheimer's Disease's cognitive and CSF biomarkers.

This manuscript presents the quantification and correlation of three aspects of Alzheimer's Disease evolution, including structural, biochemical, and cognitive assessments. We aimed to test a novel structural biomarker for neurodegeneration based on a cortical folding model for mammals. Our central hypothesis is that the cortical folding variable, representative of axonal tension in white matter, is an optimal discriminator of pathological aging and correlates with altered loadings in Cerebrospinal Fluid samples and a decline in cognition and memory. We extracted morphological features from T1w 3T MRI acquisitions using FreeSurfer from 77 Healthy Controls (age = 66 ± 8.4, 69% females), 31 Mild Cognitive Impairment (age = 72 ± 4.8, 61% females), and 13 Alzheimer's Disease patients (age = 77 ± 6.1, 62% females) of recruited volunteers in Brazil to test its discriminative power using optimal cut-point analysis. Cortical folding distinguishes the groups with reasonable accuracy (Healthy Control-Alzheimer's Disease, accuracy = 0.82; Healthy Control-Mild Cognitive Impairment, accuracy = 0.56). Moreover, Cerebrospinal Fluid biomarkers (total Tau, A[Formula: see text]1-40, A[Formula: see text]1-42, and Lipoxin) and cognitive scores (Cognitive Index, Rey's Auditory Verbal Learning Test, Trail Making Test, Digit Span Backward) were correlated with the global neurodegeneration in MRI aiming to describe health, disease, and the transition between the two states using morphology.

Reorganization of thalamocortical connections in congenitally blind humans.

Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain structures. However, despite multiple efforts, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear. We mapped thalamocortical connectivity and assessed the integrity of white matter of 10 congenitally blind individuals and 10 sighted controls. We hypothesized an aberrant thalamocortical pattern of connectivity taking place in the absence of visual stimuli from birth as a potential mechanism of cross-modal plasticity. In addition to the impaired microstructure of visual white matter bundles, we observed structural connectivity changes between the thalamus and occipital and temporal cortices. Specifically, the thalamic territory dedicated to connections with the occipital cortex was smaller and displayed weaker connectivity in congenitally blind individuals, whereas those connecting with the temporal cortex showed greater volume and increased connectivity. The abnormal pattern of thalamocortical connectivity included the lateral and medial geniculate nuclei and the pulvinar nucleus. For the first time in humans, a remapping of structural thalamocortical connections involving both unimodal and multimodal thalamic nuclei has been demonstrated, shedding light on the possible mechanisms of cross-modal plasticity in humans. The present findings may help understand the functional adaptations commonly observed in congenitally blind individuals.

Rol de la Comisión Honoraria para la Lucha Antituberculosa y Enfermedades Prevalentes en la Estrategia Nacional de Vacunación contra la COVID-19 en Uruguay: período noviembre 2020 - julio 2021 / Role of the Honorary Commission for the Fight against Tuberculosis and Prevalent Diseases (CHLA-EP) in the National Vaccination Strategy against COVID-19 in Uruguay: november 2020 - July 2021 / Papel da Comissão Honorária de Luta contra a Tuberculose e Doenças Prevalentes (CHLA-EP) na Estratégia Nacional de Vacinação contra a COVID-19 no Uruguai: período de novembro de 2020 a julho de 2021

La pandemia por la infección por el nuevo coronavirus SARS-CoV-2 determinó que en Uruguay a inicio de marzo de 2020 el gobierno diseñara el Plan Nacional de Contingencia para la enfermedad COVID-19 causada por este virus. Este plan incluyó medidas preventivas no farmacológicas como: higiene de manos, distanciamiento físico, uso de mascarilla de diferentes tipos de acuerdo al riesgo de quien debía utilizarlos, en algunos períodos restricciones varias sobre circulación de personas, actividades educativas o espectáculos públicos, y tránsitos por tierra, aire o mar. Se apeló fuertemente a la libertad responsable. A partir de diciembre 2020 se decidió incorporar a la prevención primaria una Estrategia de Vacunación. El 1/3/2021 se inició la Campaña Vacunación COVID-19 2021, que fue no obligatoria, poblacional, inicialmente para personas mayores de 18 años y a partir de junio incluyó adolescentes entre 12 y 17 años y mujeres embarazadas. El Grupo Asesor Científico Honorario (GACH) del Gobierno Nacional junto a la Comisión Nacional Asesora de Vacunas (CNAV) del Ministerio de Salud Pública (MSP) que cuenta con largos años de aconsejar a las autoridades sanitarias en decisiones científicas sobre la introducción de vacunas, y una Comisión ad Hoc creada para vacunas COVID-19 reunieron a expertos del país para asesorar sobre la estrategia de vacunación. La Comisión Honoraria para la Lucha Antituberculosa y Enfermedades Prevalentes (CHLA-EP) como brazo operativo del Departamento de Inmunizaciones del MSP estuvo desde el mes de diciembre involucrada con todos los actores para implementar la Campaña de Vacunación poblacional COVID-19 sin descuidar las tareas que le competen en la vacunación para prevenir otras enfermedades infecciosas. Metodología: se realizó un estudio descriptivo, retrospectivo de las estrategias implementadas por el Dpto. Operativo de Inmunizaciones (brazo operativo del Departamento de Inmunizaciones del MSP), Laboratorio A. Calmette, Comisión Honoraria, Coordinación General y los departamentos administrativos: entre los meses de noviembre de 2020 a julio de 2021. Fuente de datos: informes difundidos o aportados especialmente para este trabajo por el Dpto. Operativo de Inmunizaciones, Laboratorio A. Calmette, Dpto. de Inmunizaciones del Ministerio de Salud Pública, Recursos Humanos, Recursos Materiales, Servicio de Apoyo, Comunicación y Diseño, Centros Periféricos, Dirección Ejecutiva y Secretaría General. Resultados: se muestran los resultados de 4 períodos: 1) planificación (noviembre-diciembre 2020); 2) capacitación, contratación de recursos humanos y asesoramiento para la adquisición de recursos materiales (enero-febrero 2021); 3) apertura de centros (hubs), puestos de vacunación COVID-19 y puesta en marcha de la Campaña COVID-19 (marzo 2021); 4) superposición campaña antigripal 2021 (abril-junio 2021) y mantenimiento coberturas de las vacunas del (PNI) 1. Planificación: se tomaron en cuenta las características de las vacunas que se recibirían vacunas a virus muertos, vacunas vectoriales y en particular la RNAm con requerimiento de almacenamiento a -70ºC, traslado y distribución a -25ºC, y reconstitución y uso a +28ºC en los diferentes escenarios. Se realizó análisis de riesgo y análisis de costo. Se intercambió con diferentes empresas que brindan dicho servicio, participando de actividades de capacitación con alguna de ellas, fundamentales a la hora de diseñar una cadena de frío sólida y sin fallas (por ejemplo actividad de entrenamiento con Vac-Q-tec). Se diseñó el traslado de las vacunas hacia los hubs, vacunatorios terciarios o centros periféricos de vacunación. Teniendo en cuenta el sitio de llegada de las vacunas, se plantearon los diferentes escenarios posibles, no solo a nivel central (Montevideo-Aeropuerto Internacional de Carrasco), sino también a nivel nacional utilizando las diferentes terminales aéreas. Así también se planificaron estrategias de distribución de las vacunas por vía terrestre involucrando diferentes actores (públicos o privados), basados en la experiencia de la institución debido al cotidiano trabajo que realizan, tanto en campaña de vacunación como en el mantenimiento del PNI. Se realizó la previsión de compras de insumos para el almacenamiento y distribución de la vacuna, como para la vacunación en sí. Se trabajó en conjunto con Departamento de Compras de Ministerio de Economía y Dirección de Secretaria del MSP. Se participó en la conformación de equipos de vacunación con la consigna de vacunación rápida, universal, gratuita y segura. Se estableciendo roles por equipo de vacunación constituidos por 6 personas. 2. Capacitación, contratación de recursos humanos y asesoramiento para la adquisición de recursos materiales. Se confeccionaron cursos y materiales en calidad y cantidad para que el personal adquiriera conocimientos actualizado sobre SARS-CoV-2 y COVID-19, mecanismos de transmisión, utilización y planificación de uso de equipos de protección personal (EPP) y seguimiento detallado de las vacunas en desarrollo. Análisis minucioso de los posibles candidatos a llegar a Uruguay, focalizándose en tres de ellos (Pfizer BioNtech, CoronaVac, Oxford AZ). Se realizó capacitación por roles (vacunadores, preparadores, administradores, referente de puesto, backup). Especial énfasis tuvo la capacitación en el cuidado de la persona a vacunar, registro del acto vacunal, cadena de frío en todos sus puntos, descarte de materiales utilizados y llenado de planillas de fiscalización. Todos los contenidos y materiales quedaron disponibles en la página web de la institución. Recursos humanos: se destinaron funcionarios para la confección, firma y papeleo de altas de 1.463 nuevos contratos de los equipos de todo el país, RRHH dedicados no sólo a la vacunación en sí, sino a participar activamente en cada uno de los puestos de vacunación. Esto significó que el trabajo se multiplicó por seis para las tareas requeridas durante este período. El Dpto. Recursos Materiales pasó de empaquetar y distribuir de 7 a 15 paquetes a 80 paquetes mensuales para cada centro periférico/vacunatorio. El envío habitual de materiales se cuadruplicó y en los comienzos de la campaña se llegó a quintuplicar y sextuplicar. Algunas de las cifras a destacar son: 3.300.000 jeringas con aguja, 8.800 Litros de alcohol eucaliptado, 852.000 guantes de látex y nitrilo y 141.000 sobreáticos. 3. Apertura de centros (hubs), puestos de vacunación COVID-19 y puesta en marcha de la Campaña COVID-19. Esto generó en forma progresiva la habilitación de centros (hubs) de máxima respuesta (vacunación masiva): ocho en Montevideo, uno en Canelones y uno en Maldonado. Dado que se decidió vacunar de 3 a 5 personas cada 15 minutos, en el hub del Hospital de Clínicas se administaron 211.153 dosis en sus 32 puestos de vacunación y en el hub Antel Arena se administraron 615.637 dosis en sus 15 puestos de vacunación. Al 31 de julio habían 144 puestos de vacunación COVID 19 habilitados en todo el territorio Nacional. La distribución se realizó a nivel nacional: 3.229. 320 dosis de vacuna Sinovac, 97.790 dosis de vacunas AstraZeneca y 1.585452 de vacuna Pfizer. Se participó en la conformación de 60 equipos con un referente (identificación, registro, control), preparador, 2 vacunadores y chofer para la vacunación en los Establecimientos de Larga Estadía de Personas Mayores (ELEPEM) y personas con situaciones especiales. Se participó activamente en la vacunación en ELEPEM, refugios y escuelas especiales, visitándose un total de 1679 Instituciones y se vacunaron 35.006 personas. 4. Superposición campaña antigripal 2021 (abril-junio 2021) y mantenimiento coberturas de las vacunas del (PNI). A partir del 24/04/2021 comenzó la Campaña Antigripal 2021, superponiéndose a la campaña descripta de COVID-19, lo que implicó reforzar las estrategias y ampliar las acciones para poder cumplir con ambas campaña paralelamente, siempre con el objetivo de no desatender el Programa Nacional de Inmunizaciones. Dentro de ésta se llevó a cabo la vacunación en los ELEPEM, como anualmente realiza la comisión y vacunación en territorio de vacunas COVID-19, antigripal y del PNI. Según los datos recibidos al 17 de Julio en el informe de la Unidad de Inmunizaciones del MSP (semana 12), fueron 605.802 dosis registradas, de las cuales al menos 87.802 dosis fueron administradas por la institución. Esta diferencia en relación a las campañas anteriores podría ser atribuida al intenso trabajo realizado en la estrategia de vacunación COVID-19. En el marco de la actividad interinstitucional barrio a barrio las personas vacunadas con vacuna antigripal en el móvil de la CHLA-EP en Montevideo fueron 7.225. La CHLA-EP ha contribuido desde la logística y la vacunación con esquema de dos dosis para las tres plataformas y una dosis de refuerzo para los que recibieron vacunas a virus muertos. La CHLA-EP ha contribuido para alcanzar las cifras de la Campaña de Vacunación COVID-19 entre el 1/3 y el 29/8/21: 5.487.181 dosis aplicadas, 2.65.269 personas que recibieron una dosis de vacuna y de ellas 2.496.290 tienen dos dosis y han recibido dosis de refuerzo 333.662. Conclusiones: la planificación, capacitación, provisión de recursos humanos y materiales lograron llevar a cabo dos campañas de vacunación coexistentes en hubs, vacunatorios, ELEPEM y en territorio que se han considerado exitosas e históricas.

The new Coronavirus SARS CoV-2 pandemic was declared at the beginning of March 2020 when the Uruguayan government appointed the National Contingency Plan for the COVID-19 disease caused by this virus. This plan included non-pharmacological preventive measures such as: hand hygiene, physical distancing, use of different types of masks according to the risk of who should wear them, in some periods, restrictions to mobility, educational activities or public shows, and movement by land, air or sea. Responsible freedom was strongly called for. In December 2020, the Vaccination Strategy was included as a primary prevention mechanism. On 3/1/2021, the COVID-19 2021 Vaccination Campaign began, it was non-mandatory, population-based, initially for people over 19 years of age, and for adolescents between 12 and 17 years of age and pregnant women since June. The National Honorary Scientific Advisory Group (GACH) together with the National Vaccine Advisory Committee (CNAV) of the Ministry of Public Health (MSP) that has vast experience in advising health authorities in scientific decisions on the introduction of vaccines, and an ad-Hoc Commission created for COVID-19 vaccines, brought together experts to advise on the vaccination strategy. The Honorary Commission for the Fight Against Tuberculosis and Prevalent Diseases (CHLA-EP), as the operational branch of the MSP's Department of Immunizations, has participated with all stakeholders since December to implement the COVID-19 Population Vaccination Campaign without neglecting their tasks regarding the vaccination to prevent other infectious diseases. Methodology: a descriptive, retrospective study was carried out regarding the strategies implemented by the Immunization Operational Department (operational branch of the Ministry of Health's Immunization Department), A. Calmette Laboratory, Honorary Commission, General Coordination and Administrative Departments between November, 2020 and July 2021. Data source: reports were issued or provided specially for this work by the Immunization Operational Department, A. Calmette Laboratory, by the Ministry of Public Health's immunization Department, Human Resources, Material Resources, Support, Communication and Design Service, Peripheral Centers, Executive Board and General secretariat. Results: the results of the 4 periods are as follows: 1- Planning (Period November - December 2020), 2- Training, hiring of human resources and advice for the acquisition of qualitative and quantitative material resources (January - February 2021), 3- Opening of COVID-19 vaccination centers (Hubs), posts and launch of the COVID-19 Campaign (March 2021), 4- Overlap of the 2021 flu campaign (April-June) and maintenance of vaccine coverage (National Immunization Programme - PNI). 1- Planning: The characteristics of the different vaccines (dead virus vaccines, vector vaccines and in particular mRNA vaccines, with storage requirements of -70ºC, transfer and distribution requirements of -25ºC, and reconstitution and use of +2 + 8ºC) were taken into account in the different scenarios. Risk and costs analysis were performed. We interchanged data with different companies that provided this service, we participated in training activities with some of them, mainly in the design of a solid cold chain without failures (e.g. a Vac-Q-tec training activity). The transfer of vaccines to hubs, tertiary vaccination centers or peripheral vaccination centers was designed. The different destination site of the vaccines, the different possible scenarios were taken into account, both at local central level (Montevideo - Carrasco International Airport), but also at National level using the different air terminals. Similarly, strategies for the distribution of vaccines by land were planned involving different public or private actors based on the institutions' experience, both regarding the vaccination campaign and in the PNI maintenance. We made a supply acquisition plan for the vaccine's storage and distribution, for the vaccination itself, and for the purchase of supplies jointly with the Procurement Department of the Ministry of Economy and Executive Secretariat of the MSP. Six-people vaccination teams were created with clear roles and with the slogan of rapid, universal, free and safe vaccination for all. 2- Training: Courses and materials were organized for the staff to acquire updated knowledge about SARS CoV 2 and COVID-19, transmission mechanisms, use and planning of use of personal protective equipment (PPE) and of course, a detailed monitoring of the vaccines being developed. We carried out a thorough analysis of the vaccine companies to arrive in Uruguay, we focused on 3 of them (Pfizer BioNtech, CoronaVac, Oxford AZ). Training was carried out by roles (vaccinators, preppers, administrators, position referents, backups). Special emphasis was placed on the training of the care of the person to be vaccinated, registration of the vaccination act, end-to-end cold chain, disposal of used materials and filing out inspection forms. All the contents and materials were available on the Institution's webpage. Human resources: human resources were allocated for the creation, signature and registration of the paperwork for 1,463 new contracts for teams across the country. These resources were allocated not only to vaccination itself, but also to actively participate in each of the vaccination posts. This meant that the work was multiplied by 6 for the tasks required during this period. The Department of Material Resources, went from packaging and distributing from 7 to 15 packages a month to 80 packages a month for each Peripheral/Vaccination Center. Material shipment quadrupled at the beginning of the campaign and it eventually grew by five and sixfold. Some of the key figures to highlight are: 3, 300,000 needle syringes, 8,800 liters of Eucalyptus Alcohol, 852,000 latex and nitrile gloves and 141,000 isolation gowns. 3. COVID-19 Vaccination Hubs, Posts and Campaigns. We gradually opened maximum response mass vaccination Hubs in Montevideo (8), Canelones (1) and Maldonado (1). Since it was had been decided to vaccinate 3 to 5 people every 15 minutes, the primary results at the Hospital de Clínicas Hub were 211,153 doses administered in 32 vaccination posts, and at Antel Arena Hub 615,637 doses were administered in its 15 vaccination posts. As of July 31, there were 144 COVID 19 vaccination posts throughout the national territory. The distribution was made nationwide: 3,229,320 Sinovac vaccine doses, 97,790 Oxford-Astra Zeneca vaccine doses, and 1,585,452 Pfizer-BioNtech vaccine doses. We devised 60 teams including a referent (identification, registration, control), a trainer, 2 vaccinators and vaccination driver for Homes for the Elderly at ELEPEM and people needing special care. They actively participated in the vaccination at ELEPEM, Shelters and Schools for Children with Special Needs and visited a total of 1679 Institutions and overall, 35,006 people were vaccinated. 4- Overlap of the 2021 flu campaign (April-June) and the maintenance of the COVID vaccine coverage (National Immunization Programme - PNI). Since 04/24/2021, the Anti-Flu Campaign began, and it overlapped the COVID-19 campaign described above, which meant reinforcing strategies and expanding actions to be able to carry out both campaigns simultaneously, always with the objective of maintaining the National Immunization Program. Vaccination was carried out at the ELEPEM, as it is performed annually by the commission and vaccination of COVID-19, influenza and PNI was performed on the territory. According to the data received on July 17 in the Ministry of Public Health Immunization Unit Report (week 12), there were 605,802 registered doses, of which at least 87,802 had been administered by the Institution. This difference regarding previous campaigns could have been caused by the intense work carried out during the COVID19 Vaccination Campaign. Within the framework of the inter-institutional activity "Barrio a Barrio" (Vaccination in all Neighborhoods), 7,225 people were vaccinated with the influenza vaccine at the CHLA-EP mobile vaccination bus in Montevideo. The CHLA-EP has contributed with logistics and vaccination with a 2-dose schedule for the 3 platforms and a booster dose for those who received virus vaccines. The CHLA-EP has contributed to achieving the target of the COVID-19 Vaccination Campaign between 1/3 and 8/29/21: 5,487,181 doses were applied, 2,065,269 people received 1 dose of vaccine and 2,496,290 of them received 2 doses and 333,662 have received booster doses. Conclusion: the planning, training, provision of human and material resources has enabled us to successfully carry out two historical simultaneous vaccination campaigns in hubs, vaccination centers, ELEPEM and all along the territory.

A pandemia causada pela infecção pelo novo Coronavírus SARS CoV-2 determinou que no Uruguai no início de março de 2020 o governo elaborasse o Plano Nacional de Contingência para a doença COVID-19 causada por este vírus. Este plano incluía medidas preventivas não farmacológicas como: higiene das mãos, distanciamento físico, uso de diferentes tipos de máscaras dependendo do risco de quem as deve usar, em alguns períodos várias restrições à circulação de pessoas, atividades educativas ou espetáculos públicos e a trânsito por terra, ar ou mar). Foi feito um forte apelo à liberdade responsável. A partir de dezembro de 2020, decidiu-se incorporar uma Estratégia de Vacinação à prevenção primária. Em 01/03/2021 teve início a Campanha de Vacinação COVID-19 2021, não obrigatória, de base populacional, inicialmente para maiores de 18 anos e a partir de junho contempla adolescentes entre 12 e 17 anos e gestantes. O Grupo Honorário de Assessoramento Científico do Governo Nacional juntamente com a Comissão Nacional de Assessoramento de Vacinas (CNAV) do Ministério da Saúde Pública (MSP), que assessora autoridades de saúde em decisões científicas sobre a introdução de vacinas, e uma Comissão ad hoc criada para vacinas contra a COVID-19 reuniu especialistas do país para aconselhar sobre a estratégia de vacinação. A Comissão Honorária de Luta contra a Tuberculose e Doenças Prevalentes (CHLA-EP) como braço operacional do Departamento de Vacinação do MSP envolveu-se desde dezembro com todos os intervenientes na implementação da Campanha de Vacinação da População COVID-19, aliás de realizar as tarefas de vacinação para prevenir outras doenças infecciosas. Metodologia: foi realizado um estudo descritivo e retrospectivo das estratégias implementadas pelo Departamento Operacional de Imunizações (braço operacional do Departamento de Imunizações do MSP), Laboratório A. Calmette, Comissão Honorária, Coordenação Geral e departamentos administrativos: entre os meses de novembro de 2020 a julho de 2021. Fonte de dados: relatórios divulgados ou oferecidos especialmente para este trabalho pelo Departamento Operacional de Imunizações, Laboratório A. Calmette, Departamento de Imunizações do Ministério da Saúde Pública, Recursos Humanos, Recursos Materiais, Serviço de Apoio, Comunicação e Design, Centros Periféricos, Direção Executiva e Secretaria Geral. Resultados: são apresentados os resultados de 4 períodos: 1- Planejamento (novembro - dezembro de 2020), 2- Capacitação, contratação de recursos humanos e assessoria para aquisição de recursos materiais em qualidade e quantidade (janeiro - fevereiro de 2021), 3- Abertura de centros (Hubs), postos de vacinação COVID-19 e implementação da Campanha COVID-19 (março 2021), 4- Sobreposição da campanha da gripe 2021 (abril-junho 2021) e manutenção da cobertura vacinal (PNI) 1- Planejamento: As características das vacinas a receber eram vacinas de vírus mortos, vacinas vetoriais e em particular mRNA com requisitos de armazenamento de temperaturas de -70ºC, transferência e distribuição de -25ºC, e reconstituição e uso de +2 +8ºC nos diferentes cenários. Análise de risco e análise de custo foram realizadas. Realizaram-se intercâmbios com diferentes empresas que prestam este serviço, participando em ações de formação com algumas delas, essenciais na criação de uma cadeia de frio sólida e sem falhas (ex. ação de formação com Vac-Q-tec). Foi projetada a transferência de vacinas para os hubs, centros de vacinação terciários ou periféricos. Tendo em conta o local de chegada das vacinas, foram considerados os diferentes cenários possíveis, não só a nível central (Montevidéu - Aeroporto Internacional de Carrasco), mas também a nível nacional utilizando os diferentes terminais aéreas. Da mesma forma, foram planejadas estratégias de distribuição de vacinas por via terrestre envolvendo diferentes atores (públicos ou privados), com base na experiência da instituição, tanto na campanha de vacinação quanto na manutenção do PNI. A previsão de compra de insumos foi feita tanto para o armazenamento e distribuição da vacina, quanto para a própria vacinação, como também na tomada de decisão na compra de insumos, atuando em conjunto com o Departamento de Compras do Ministério da Economia e Gestão Secretário do MSP. Eles participaram da formação de equipes de 6 pessoas com funções especificas de vacinação com o slogan de vacinação rápida, universal, gratuita e segura. 2- Capacitação, contratação de recursos humanos e assessoria para aquisição de recursos materiais em qualidade e quantidade. Foram organizados cursos e materiais para que os funcionários adquirissem conhecimento atualizado sobre SARS CoV2 e COVID-19, mecanismos de transmissão, uso e planejamento de uso de equipamentos de proteção individual (EPI) e também para o acompanhamento minucioso das vacinas em desenvolvimento. Fizemos a análise minuciosa das possíveis vacinas candidatas para chegar ao Uruguai, e focamos em 3 delas (Pfizer BioNtech, CoronaVac, Oxford AZ). O treinamento foi realizado por funções (vacinadores, treinadores, administradores, posição de referência, backup). Foi dado especial destaque à formação no cuidado da pessoa a vacinar, registo do ato vacinal, rede de frio em todos os seus pontos, eliminação de materiais utilizados e preenchimento de fichas de controlo. Todos os conteúdos e materiais foram disponibilizados na página web da Instituição. Recursos humanos: funcionários foram alocados para a preparação, assinatura e registro de 1.463 novos contratos para complementar as equipes em todo o país, estes recursos humanos estiveram dedicados não apenas à vacinação em si, mas a participar ativamente de cada um dos postos de vacinação. Isso significou que o trabalho se multiplicou por 6 para as tarefas exigidas durante esse período. O Departamento de Recursos Materiais, passou de embalar e distribuir de 7 para 15 embalagens por mês, passando para 80 embalagens para cada Periférico/Centro de Vacinação. A remessa habitual de materiais se quadruplicou e no início da campanha aumentou cinco e seis vezes. Alguns dos números a destacar são: 3.300.000 seringas com agulha, 8.800 litros de álcool de eucalipto, 852.000 luvas de látex e nitrílica e 141.000 túnicas. 3. Abertura de centros e postos de vacinação COVID-19 e lançamento da Campanha COVID-19. Isso gerou progressivamente o estabelecimento de centros de resposta máxima (Hubs) (vacinação em massa) 8 em Montevidéu, um em Canelones e um em Maldonado. Já que decidiu-se vacinar de 3 a 5 pessoas a cada 15 minutos, no Hub. O Hospital de Clínicas administrou 211.153 doses em seus 32 postos de vacinação e na Arena Hub Antel foram administradas 615.637 doses em seus 15 postos de vacinação. Até 31 de julho, havia 144 postos de vacinação contra a COVID 19 habilitados em todo o território nacional. A distribuição foi realizada, 3.229 foram distribuídos em todo o país, 320 doses de vacina Sinovac, 97.790 doses de vacinas AstraZeneca e 1.585452 de vacina Pfizer. Participaram no treinamento de 60 equipes de referência (identificação, registo, controle), treinador, 2 vacinadores e motorista para vacinação em estabelecimentos de longa permanência para idosos (ELEPEM) e pessoas com situações especiais em albergues e escolas especiais, visitando um total de 1.679 Instituições e vacinando a 35.006 pessoas. 4- Sobreposição da campanha de gripe de 2021 (abril a junho de 2021) e manutenção da cobertura vacinal (PNI). A partir de 24/04/2021 teve início a Campanha da Gripe 2021, sobrepondo-se à campanha COVID-19 descrita, o que implicou o reforço de estratégias e ampliação das ações para poder cumprir ambas campanhas em paralelo, sempre com o objetivo de não descurar o Programa Nacional de Imunizações. Foi realizada a vacinação no ELEPEM, conforme anualmente realizada pela comissão e a vacinação no território das vacinas COVID-19, influenza e PNI. De acordo com os dados recebidos até 17 de julho no relatório da Unidade de Imunizações dos Ministérios da Saúde Pública (semana 12), foram registradas 605.802 doses, das quais pelo menos 87.802 doses foram administradas pela Instituição. Essa diferença em relação às campanhas anteriores pode ser atribuída ao intenso trabalho realizado na estratégia de Vacinação COVID19. No âmbito da atividade interinstitucional Bairro a Bairro, 7.225 pessoas foram vacinadas com a vacina contra gripe no celular do CHLAEP de Montevidéu. O CHLA-EP tem contribuído desde a logística e vacinação com um esquema de 2 doses para as 3 plataformas e uma dose de reforço para quem recebeu vacinas de vírus mortos. O CHLA-EP contribuiu para atingir os números da Campanha de Vacinação COVID-19 entre 1/3 e 29/8/21: 5.487.181 doses aplicadas, 2.065.269 pessoas que receberam 1 dose de vacina e delas 2.496.290 têm 2 doses e 333.662 receberam doses de reforço. Conclusões: O planejamento, capacitação, disponibilização de recursos humanos e materiais permitiram a realização de duas campanhas de vacinação coexistentes nos hubs, vacinatórios, ELEPEM e no território, o que pode ser considerado um processo bem sucedido e histórico.

Effect of gastric acid on the surface roughness and bacterial adhesion of bulk-fill composite resins.

The purpose of this in vitro study was to evaluate the effect of gastric acid on the surface roughness and biofilm formation of bulk-fill composite resins. Twenty-seven samples of each composite resin were obtained: G1: Filtek Z250 XT (Z250), G2: Filtek Bulk Fill (FTK), G3: Tetric N-Ceram Bulk Fill (TTC), and G4: Aura Bulk Fill (AUR). The samples were quantitatively analyzed for surface roughness (Ra) using a roughness tester (n=15) and for biofilm formation (Cn) by the counting of colony-forming units (CFUs/mL) (n=9) in three different moments: after polishing (Ra0 and Cn0), after gastric acid immersion (Ra1 and Cn1), and after gastric acid and simulated tooth brushing (Ra2 and Cn2). Qualitative analysis through surface topography (n=3) was evaluated by scanning electron microscopy (SEM). Ra values were subjected to two-way repeated measures ANOVA, followed by Tukey's test. Cn values were subjected to Kruskal-Wallis analysis, followed by multiple comparisons analysis (α=0.05). Z250 and FTK showed significant increases in surface roughness at Ra1. There were fewer CFUs/mL on TTC and AUR in relation to those of Z250 and FTK for Cn0, Cn1 and Cn2. The SEM images showed that gastric acid increased the formation of cracks, exposure of fillers and micro cavities for all composite resins. After tooth brushing, the topographical changes were more evident but did not influence biofilm formation. The gastric acid promoted both degradation of the surfaces and bacterial adhesion for all composite resins.

Effect of gastric acid on the surface roughness and bacterial adhesion of bulk-fill composite resins

Abstract The purpose of this in vitro study was to evaluate the effect of gastric acid on the surface roughness and biofilm formation of bulk-fill composite resins. Twenty-seven samples of each composite resin were obtained: G1: Filtek Z250 XT (Z250), G2: Filtek Bulk Fill (FTK), G3: Tetric N-Ceram Bulk Fill (TTC), and G4: Aura Bulk Fill (AUR). The samples were quantitatively analyzed for surface roughness (Ra) using a roughness tester (n=15) and for biofilm formation (Cn) by the counting of colony-forming units (CFUs/mL) (n=9) in three different moments: after polishing (Ra0 and Cn0), after gastric acid immersion (Ra1 and Cn1), and after gastric acid and simulated tooth brushing (Ra2 and Cn2). Qualitative analysis through surface topography (n=3) was evaluated by scanning electron microscopy (SEM). Ra values were subjected to two-way repeated measures ANOVA, followed by Tukey's test. Cn values were subjected to Kruskal-Wallis analysis, followed by multiple comparisons analysis (α=0.05). Z250 and FTK showed significant increases in surface roughness at Ra1. There were fewer CFUs/mL on TTC and AUR in relation to those of Z250 and FTK for Cn0, Cn1 and Cn2. The SEM images showed that gastric acid increased the formation of cracks, exposure of fillers and micro cavities for all composite resins. After tooth brushing, the topographical changes were more evident but did not influence biofilm formation. The gastric acid promoted both degradation of the surfaces and bacterial adhesion for all composite resins.

Resumo O objetivo deste estudo in vitro foi avaliar o efeito do ácido gástrico na rugosidade superficial e na formação do biofilme nas resinas compostas de incremento único. Vinte e sete amostras de cada resina composta foram confeccionadas: G1: Filtek Z250 XT (Z250), G2: Filtek Bulk Fill (FTK), G3: Tetric N-Ceram Bulk Fill (TTC), and G4: Aura Bulk Fill (AUR). As amostras foram analisadas quantitativamente quanto à rugosidade da superfície (Ra) usando um rugosímetro (n=15) e para formação de biofilme (Cn) pela contagem de unidades formadoras de colônias (UFC/mL) (n=9) em três diferentes momentos: após polimento (Ra0 and Cn0), após imersão em ácido gástrico (Ra1 and Cn1), e após ácido gástrico e simulação de escovação (Ra2 and Cn2). Análise qualitative da topografia superficial (n=3) foi avaliada por meio de microscopia eletrônica de varredura (MEV). Os valores de Ra foram analisados pela ANOVA de duas vias para amostras pareadas, seguido do teste de Tukey. Os valores de Cn foram submetidos ao teste de Kruskal-Wallis, seguido da análise de comparações múltiplas (α=0,05). Z250 e FTK tiveram aumento significativo na rugosidade superficial em Ra1. Houve menos CFUs/mL para TTC e AUR em relação à Z250 e FTK em Cn0, Cn1 and Cn2. As imagens em MEV mostraram que o ácido gástrico aumentou a formação de fendas, exposição das partículas e mcrocavidades para todas as resinas compostas. Após escovação, as mudanças topográficas foram mais evidentes, mas não influenciou na formação do biofilme. O ácido gástrico promoveu degradação da superfície e adesão bacteriana para todas as resinas compostas.

Copper-coated hospital surfaces: reduction of total bacterial loads and resistant Acinetobacter spp.

Healthcare-associated infections (HAIs) represent a global challenge and an even more staggering concern when related to microorganisms capable of resisting and surviving for long periods in the environment, such as Acinetobacter spp. Strategies that allow a reduction of pathogens from hospital environments represent an additional barrier in infection control protocols, minimizing transmission to hospitalized patients. Considering the antimicrobial properties of copper, here, the bacterial load and the presence of Acinetobacter spp. were monitored on high handling surfaces covered by 99.9% copper films on intensive and non-intensive care unit bedrooms in a tertiary care hospital. Firstly, copper-coated films were able to inhibit the adhesion and biofilm formation of A. baumannii strains in in vitro assays. On the other hand, Acinetobacter spp. were isolated from both copper-coated and uncoated surfaces in the hospital, although the majority was detected on surfaces without copper. All carbapenem-resistant A. baumannii isolates identified harbored the blaoxa-23 gene, while the A. nosocomialis isolates were susceptible to most antimicrobials tested. All isolates were susceptible to polymyxin B. Regarding the total aerobic bacteria, surfaces with copper-coated films presented lower total loads than those detected for controls. Copper coating films may be a workable strategy to mitigate HAIs, given their potential in reducing bacterial loads in nosocomial environments, including threatening pathogens like A. baumannii.

Impact of Ca2+-Induced PI(4,5)P2 Clusters on PH-YFP Organization and Protein-Protein Interactions.

Despite its low abundance, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a key modulator of membrane-associated signaling events in eukaryotic cells. Temporal and spatial regulation of PI(4,5)P2 concentration can achieve localized increases in the levels of this lipid, which are crucial for the activation or recruitment of peripheral proteins to the plasma membrane. The recent observation of the dramatic impact of physiological divalent cation concentrations on PI(4,5)P2 clustering, suggests that protein anchoring to the plasma membrane through PI(4,5)P2 is likely not defined solely by a simple (monomeric PI(4,5)P2)/(protein bound PI(4,5)P2) equilibrium, but instead depends on complex protein interactions with PI(4,5)P2 clusters. The insertion of PI(4,5)P2-binding proteins within these clusters can putatively modulate protein-protein interactions in the membrane, but the relevance of such effects is largely unknown. In this work, we characterized the impact of Ca2+ on the organization and protein-protein interactions of PI(4,5)P2-binding proteins. We show that, in giant unilamellar vesicles presenting PI(4,5)P2, the membrane diffusion properties of pleckstrin homology (PH) domains tagged with a yellow fluorescent protein (YFP) are affected by the presence of Ca2+, suggesting direct interactions between the protein and PI(4,5)P2 clusters. Importantly, PH-YFP is found to dimerize in the membrane in the absence of Ca2+. This oligomerization is inhibited in the presence of physiological concentrations of the divalent cation. These results confirm that cation-dependent PI(4,5)P2 clustering promotes interactions between PI(4,5)P2-binding proteins and has the potential to dramatically influence the organization and downstream interactions of PI(4,5)P2-binding proteins in the plasma membrane.

Neural Correlates of Listening to Varying Synchrony Between Beats in Samba Percussion and Relations to Feeling the Groove.

Listening to samba percussion often elicits feelings of pleasure and the desire to move with the beat-an experience sometimes referred to as "feeling the groove"- as well as social connectedness. Here we investigated the effects of performance timing in a Brazilian samba percussion ensemble on listeners' experienced pleasantness and the desire to move/dance in a behavioral experiment, as well as on neural processing as assessed via functional magnetic resonance imaging (fMRI). Participants listened to different excerpts of samba percussion produced by multiple instruments that either were "in sync", with no additional asynchrony between instrumental parts other than what is usual in naturalistic recordings, or were presented "out of sync" by delaying the snare drums (by 28, 55, or 83 ms). Results of the behavioral experiment showed increasing pleasantness and desire to move/dance with increasing synchrony between instruments. Analysis of hemodynamic responses revealed stronger bilateral brain activity in the supplementary motor area, the left premotor area, and the left middle frontal gyrus with increasing synchrony between instruments. Listening to "in sync" percussion thus strengthens audio-motor interactions by recruiting motor-related brain areas involved in rhythm processing and beat perception to a higher degree. Such motor related activity may form the basis for "feeling the groove" and the associated desire to move to music. Furthermore, in an exploratory analysis we found that participants who reported stronger emotional responses to samba percussion in everyday life showed higher activity in the subgenual cingulate cortex, an area involved in prosocial emotions, social group identification and social bonding.

Percepções de enfermeiros sobre Higiene Bucal em Unidades de Terapia Intensiva adulto / Nurses' perceptions about oral hygiene in adult intensive care units

Objetivo: apreender as percepções de enfermeiros sobre higiene bucal em adultos internados em terapia intensiva. Método: pesquisa qualitativa feita com nove enfermeiros de duas unidades de terapia intensiva adulto de um hospital universitário público de grande porte do Norte do Estado do Paraná, Brasil. Utilizou-se entrevista semiestruturada audiogravada, sendo os dados transcritos e tratados pela análise de conteúdo. Resultados: emergiram duas categorias empíricas: A importância da higiene bucal na visão dos enfermeiros e; O papel do enfermeiro na concretização da higiene bucal. Conclusão: embora os participantes reconheçam a importância da higiene bucal em vários aspectos, ainda há lacunas quanto ao entendimento de seu papel neste cuidado, bem como acerca de sua correta execução e registro no prontuário. (AU)

Objective: To understand nurses' perceptions of oral hygiene in adults in intensive care. Methodology: Qualitative research conducted with nine nurses from two adult intensive care units at a large public university hospital in the north of the state of Paraná, Brazil. Semi-structured interviews were conducted with audio recording, transcription and later examined by content analysis. Results: Two empirical categories emerged: The importance of oral hygiene in the view of nurses and; The role of the nurse in achieving oral hygiene. Conclusion: Although the participants recognize the importance of oral hygiene in several aspects, there are still gaps regarding the understanding of its role in this care, as well as about its correct execution and registration in the medical record. (AU)

Objetivo: comprender las percepciones de las enfermeras sobre higiene bucal en adultos ingresados en cuidados intensivos. Métodología: investigación cualitativa realizada con nueve enfermeras de dos unidades de cuidados intensivos para adultos en un gran hospital universitario público en el norte del estado de Paraná, Brasil. Se utilizaron entrevistas semiestructuradas grabadas en audio, los datos se transcribieron y trataron mediante análisis de contenido. Resultados: surgieron dos categorías empíricas: la importancia de la higiene bucal en opinión de las enfermeras y; El papel de la enfermera en el logro de la higiene bucal. Conclusión: Aunque los participantes reconocen la importancia de la higiene bucal en varios aspectos, todavía hay lagunas en cuanto a la comprensión de su papel en este cuidado, así como su correcta ejecución y registro en la historia clínica. (AU)

Influence of titanium and zirconia modified surfaces for rapid healing on adhesion and biofilm formation of Staphylococcus epidermidis.

OBJECTIVE: Surface alterations have been employed to enhance the osseointegration process in biomedical implants. However, these modifications may influence bacterial adhesion in different ways. Therefore, this study developed five different surfaces and evaluated the Staphylococcus epidermidis growth in early (1 h) and late (24 h) contact. DESIGN: The Titanium (Ti) and Zirconia (Zr) surfaces were divided in five groups and characterized concerning your morphology, roughness, wettability and chemical surface composition. Then, were evaluated regarding bacterial adhesion and biofilm formation/thickness, viability and morphology. RESULTS: Different topographies were manufactured resulting in a variety of combinations of surface properties. High roughness showed significantly higher bacterial adhesion in 1 h, while high hydrophilicity revealed greater bacterial proliferation in 24 h. Morphological changes were not found visually, however the viability test showed some cell membrane damage in the Ti micro and nano groups. CONCLUSIONS: Finally, surface distinct properties influence the growth of S. epidermidis independent of the based-material. Furthermore, some surface properties require precautions for use in contaminated sites according to the increased adhesion of S. epidermidis presented when in contact.

Narrative impairment, white matter damage and CSF biomarkers in the Alzheimer's disease spectrum.

BACKGROUND: Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied. OBJECTIVES: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum. RESULTS: Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aß1-42 ratio in CSF. CONCLUSIONS: AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF. METHODS: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.

Inter-method and anatomical correlates of episodic memory tests in the Alzheimer's Disease spectrum.

BACKGROUND: Episodic memory impairments have been described as initial clinical findings in the Alzheimer's Disease (AD) spectrum, which could be associated with the presence of early hippocampal dysfunction. However, correlates between performances in neuropsychological tests and hippocampal volumes in AD were inconclusive in the literature. Divergent methods to assess episodic memory have been depicted as a major source of heterogeneity across studies. METHODS: We examined correlates among performances in three different delayed-recall tasks (Rey-Auditory Verbal-Learning Test-RAVLT, Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale) and fully-automated volumetric measurements of the hippocampus (estimated using Neuroquant®) of 83 older subjects (47 controls, 27 Mild Cognitive Impairment individuals and 9 participants with Dementia due to AD). RESULTS: Inter-method correlations of episodic memory performances were at most moderate. Scores in the RAVLT predicted up to 48% of variance in HOC (Hippocampal Occupancy Score) among subjects in the AD spectrum. DISCUSSION: Tests using different stimuli (verbal or visual) and presenting distinct designs (word list, story or figure learning) may assess divergent aspects in episodic memory, with heterogeneous anatomical correlates. CONCLUSIONS: Different episodic memory tests might not assess the same construct and should not be used interchangeably. Scores in RAVLT may correlate with the presence of neurodegeneration in AD.

An MRI Study of the Metabolic and Structural Abnormalities in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric illness characterized by obsessions and/or compulsions. Its pathophysiology is still not well understood but it is known that the cortico-striatal-thalamic-cortical (CSTC) circuitry plays an important role. Here, we used a multi-method MRI approach combining proton magnetic resonance spectroscopy (H1-MRS) and diffusion tensor imaging (DTI) techniques to investigate both the metabolic and the microstructural white matter (WM) changes of the anterior cingulate cortex (ACC) in OCD patients as compared to healthy controls. Twenty-three OCD patients and 21 age-, sex-, and education-matched healthy volunteers participated in the study. Our 1H-MRS findings show increased levels of Glx in ACC in OCD. Further, significantly lower fractional anisotropy (FA) values were observed in OCD patients' left cingulate bundle (CB) as compared to healthy controls. Finally, there was a negative correlation between FA in the left CB and level of obsessions, as well as the duration of the illness. Our findings reinforce the involvement of CSTC bundles in pathophysiology of OCD, pointing to a specific role of glutamate (glutamine) and WM integrity.

Signature of survival: a 18F-FDG PET based whole-liver radiomic analysis predicts survival after 90Y-TARE for hepatocellular carcinoma.

PURPOSE: To generate a predictive whole-liver radiomics scoring system for progression-free survival (PFS) and overall survival (OS) in patients undergoing transarterial radioembolization using Yttrium-90 (90Y-TARE) for unresectable hepatocellular carcinoma (uHCC). RESULTS: The generated pPET-RadScores were significantly correlated with survival for PFS (median of 11.4 mo [95% confidence interval CI: 6.3-16.5 mo] in low-risk group [PFS-pPET-RadScore < 0.09] vs. 4.0 mo [95% CI: 2.3-5.7 mo] in high-risk group [PFS-pPET-RadScore > 0.09]; P = 0.0004) and OS (median of 20.3 mo [95% CI: 5.7-35 mo] in low-risk group [OS-pPET-RadScore < 0.11] vs. 7.7 mo [95% CI: 6.0-9.5 mo] in high-risk group [OS-pPET-RadScore > 0.11]; P = 0.007). The multivariate analysis confirmed PFS-pPET-RadScore (P = 0.006) and OS-pPET-RadScore (P = 0.001) as independent negative predictors. CONCLUSION: Pretreatment 18F-FDG PET whole-liver radiomics signature appears as an independent negative predictor for PFS and OS in patients undergoing 90Y-TARE for uHCC. METHODS: Pretreatment 18F-FDG PET of 47 consecutive patients undergoing 90Y-TARE for uHCC (31 resin spheres, 16 glass spheres) were retrospectively analyzed. For each patient, based on PET radiomics signature from whole-liver semi-automatic segmentation, PFS and OS predictive PET-radiomics scores (pPET-RadScores) were obtained using LASSO Cox regression. Using X-tile software, the optimal score to predict PFS (PFS-pPET-RadScore) and OS (OS-pPET-RadScore) served as cutoff to separate high and low-risk patients. Survival curves were estimated using the Kaplan-Meier method. The prognostic value of PFS and OS-pPET-RadScore, Barcelona-Clinic Liver Cancer staging system and serum alpha-fetoprotein level was analyzed to predict PFS and OS in multivariate analysis.

18F-FDG PET/CT predicts survival after 90Y transarterial radioembolization in unresectable hepatocellular carcinoma.

PURPOSE: To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 (90Y-TARE) for unresectable hepatocellular carcinoma (uHCC). METHODS: We analysed data from 48 patients in our prospective database undergoing 90Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent 18F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and 90Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of 18F-FDG PET/CT metabolic parameters, including SUVmax, tumour-to-liver (T/L) uptake ratio and SUVmean of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses. RESULTS: The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after 90Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUVmax (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUVmax and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUVmax and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean SUVmax; HR 2.6, 95% CI 1.1-5.9, P = 0.02, for median SUVmax:) and OS (HR 3.2, 95% CI 1-10.9, P = 0.04 for Q1 SUVmax; HR 3.7, 95% CI 1.1-12.2, P = 0.03, for Q1 T/L uptake ratio), respectively, when testing with either the BCLC staging system or serum AFP level. CONCLUSION: Lesion SUVmax and T/L uptake ratio as assessed by 18F-FDG PET/CT, but not morphological imaging, were predictive markers of survival in patients undergoing 90Y-TARE for uHCC.

Resin Versus Glass Microspheres for 90Y Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma Using Pretreatment Partition Model Dosimetry.

The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with 90Y transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD). Methods: We performed a retrospective analysis of prospectively collected data on 77 patients consecutively treated (mean age ± SD, 66.4 ± 12.2 y) for uHCC (36 uninodular, 5 multinodular, 36 diffuse) with 90Y TARE (41 resin, 36 glass) using pretreatment PMD. Study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier estimates. Several variables including Barcelona Clinic Liver Cancer (BCLC) staging system, tumor size, and serum α-fetoprotein (AFP) level were investigated using Cox proportional hazards regression. Results: The characteristics of 2 groups were comparable with regard to demographic data, comorbidities, Child-Pugh score, BCLC, serum AFP level, and 90Y global administered activity. The median follow-up time was 7.7 mo (range, 0.4-50.1 mo). Relapse occurred in 44 patients (57%) at a median of 6 mo (range, 0.4-27.9 mo) after 90Y TARE, and 41 patients (53%) died from tumor progression. Comparison between resin and glass microspheres revealed higher but not statistically significantly PFS and OS rates in the 90Y resin group than the 90Y glass group (resin PFS 6.1 mo [95% confidence interval CI, 4.7-7.4] and glass PFS 5 mo [95% CI, 0.9-9.2], P = 0.53; resin OS 7.7 mo [95% CI, 7.2-8.2] and glass OS 7 mo [95% CI 1.6-12.4], P = 0.77). No significant survival difference between both types of 90Y microspheres was observed in any subgroups of patients with early/intermediate or advanced BCLC stages. Among the variables investigated, Cox analyses showed that only in the glass group, the BCLC staging system and the serum AFP level were associated with PFS (P = 0.04) and OS (P = 0.04). Tumor size was a prognostic factor without significant influence on PFS and OS after 90Y TARE. Conclusion: Comparison between resin and glass microspheres revealed no significant survival difference in patients treated for uHCC with 90Y TARE using pretreatment PMD. Further, larger prospective studies are warranted to confirm these findings.

Partition Model-Based 99mTc-MAA SPECT/CT Predictive Dosimetry Compared with 90Y TOF PET/CT Posttreatment Dosimetry in Radioembolization of Hepatocellular Carcinoma: A Quantitative Agreement Comparison.

90Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment 99mTc-macroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of 99mTc-MAA SPECT/CT and posttreatment dosimetry based on 90Y time-of-flight (TOF) PET/CT. METHODS: We compared the 99mTc-MAA SPECT/CT results for 27 treatment sessions (25 HCC patients, 41 tumors) with 90Y SIRT (7 glass spheres, 20 resin spheres) and the posttreatment 90Y TOF PET/CT results. Three-dimensional voxelized dose maps were computed from the 99mTc-MAA SPECT/CT and 90Y TOF PET/CT data. Mean absorbed dose ([Formula: see text]) was evaluated to compute the predicted-to-actual dose ratio ([Formula: see text]) in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance ([Formula: see text]) was used to measure accuracy ([Formula: see text]) and precision (ρ). RESULTS: Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose [Formula: see text] was 240 Gy for glass and 122 Gy for resin in TVs and 72 Gy for glass and 47 Gy for resin in NTVs. [Formula: see text] was 1.46 ± 0.58 (0.65-2.53) for glass and 1.16 ± 0.41 (0.54-2.54) for resin, and the respective values for [Formula: see text] were 0.88 ± 0.15 (0.56-1.00) and 0.86 ± 0.2 (0.58-1.35). DR variability was substantially lower in NTVs than in TVs. The Lin concordance between [Formula: see text] and [Formula: see text] (resin) was significantly better for tumors larger than 150 mL than for tumors 150 mL or smaller ([Formula: see text] = 0.93 and [Formula: see text] = 0.95 vs. [Formula: see text] = 0.57 and [Formula: see text] = 0.93; P < 0.05). CONCLUSION: In 90Y radioembolization of HCC, predictive dosimetry based on 99mTc-MAA SPECT/CT provided good estimates of absorbed doses calculated from posttreatment 90Y TOF PET/CT for tumor and nontumor tissues. The low variability of [Formula: see text] demonstrates that pretreatment dosimetry is particularly suitable for minimizing radiation-induced hepatotoxicity.

Niacin metabolism and indoleamine 2,3-dioxygenase activation in malnourished patients with flaky paint dermatosis.

Flaky paint dermatosis, characterized by extensive, often bilateral areas of flaking and pigmentation, mostly in sun unexposed areas is considered a feature of kwashiorkor in both children and adults, and must be differentiated from other dermatosis, including chapped and xerotica skin, and pellagra. In this case series we provide evidence that malnourished patients with flaky paint dermatosis and infection/inflammation shown laboratory data suggestive of indoleamine 2,3-dioxygenase (IDO) activation, besides decreased urinary excretion of N1-methylnicotinamide (N1 MN), a marker of pellagra. We study nine adult patients showing flaky paint dermatosis and clinical features of infection or inflammation, and increased serum C-reactive protein, characteristic of the presence of acute phase response syndrome. As a group, they had low or deficient urinary N1 MN excretion (0.52 ± 0.39 mg/g creatinine) compatible with pellagra. They also showed low serum tryptophan levels (<29 µmol/L) and a serum kynurenine/tryptophan ratio higher than 0.04, suggesting increased IDO expression and increase in the tryptophan oxidation. Findings suggest that some patients with flaky paint dermatosis showed laboratory data suggestive of IDO activation, besides decreased N1 MN urinary excretion. Taken together, the data support the idea that flaky paint dermatosis could be a skin manifestation of niacin deficiency.

Value of a Lower-Limb Immobilization Device for Optimization of SPECT/CT Image Fusion.

UNLABELLED: The foot and the ankle are small structures commonly affected by disorders, and their complex anatomy represents a significant diagnostic challenge. By providing information on anatomic and bone structure that cannot be obtained from functional imaging, SPECT/CT image fusion can be particularly useful in increasing diagnostic certainty about bone pathology. However, because of the lengthy duration of a SPECT acquisition, a patient's involuntary movements may lead to misalignment between SPECT and CT images. Patient motion can be reduced using a dedicated patient support. We designed an ankle- and foot-immobilizing device and measured its efficacy at improving image fusion. METHODS: We enrolled 20 patients who underwent SPECT/CT of the ankle and foot with and without a foot support. The misalignment between SPECT and CT images was computed by manually measuring 14 fiducial markers chosen among anatomic landmarks also visible on bone scintigraphy. ANOVA was performed for statistical analysis. RESULTS: The absolute average difference without and with support was 5.1 ± 5.2 mm (mean ± SD) and 3.1 ± 2.7 mm, respectively, which is significant (P < 0.001). CONCLUSION: The introduction of the foot support significantly decreased misalignment between SPECT and CT images, which may have a positive clinical influence in the precise localization of foot and ankle pathology.