Analysis of modified ilib therapy in patients submitted to plastic surgery.

The sample comprised 44 volunteers who had undergone some surgical procedure and were equally divided into four groups. G1 started the therapy 24 h after the surgical procedure with the device off. G2 followed the same time pattern, 24 h, but with the device turned on. G3 and G4 started therapy three days after the surgical procedure; in G3, the device was turned off, and in G4, the device remained on during therapy; each session lasted 30 min, using 660 nm (red), energy 180 J. For all groups, the therapy started with daily use for seven days and followed the interval use of three times a week until completed 21 days. The revaluation was performed after 7 and 21 days. The results found show changes in HR at rest, systolic and diastolic BP, and in peripheral oxygen saturation, which showed a significant difference in the groups that used on-therapy (p < 0.05). In the MCGILL Scale evaluation, the mean total score showed a more accentuated drop in the groups that used ILIB, (p < 0.05). ILIB may have prevented a more significant evolution of firosis levels; however, no changes were observed in the evaluation of sleep and anxiety. The application of the ILIB in patients undergoing plastic surgery was supported in terms of hemodynamics and pain; in addition, starting the ILIB application 24 h after the procedure proved to be more advantageous.

Headache as the most prevalent post-vaccination adverse event after Covid-19 vaccination / Dor de cabeça como evento adverso pós-vacinação mais prevalente após a vacinação contra Covid-19

BACKGROUND: In 2020, the first vaccines were approved, according to the WHO. However, speculations arose regarding their efficacy and post-vaccination adverse events (AEFV). OBJECTIVE: To evaluate the prevalence of headache as AEFI from the SARSCoV-2 vaccine in Piauí, Brazil. METHODS: This is a quantitative, observational, cross-sectional, and prevalence study. Data were provided by the Post-Vaccination Adverse Event Information System (SI-AEFV), from reported cases from January to September 2021. Data were analyzed, and the research was approved by the UFPI Research Ethics Committee. RESULTS: A total of 2,008 cases were analyzed. Headache was reported in 752 cases (27.99%) as an AEFV after vaccination against SARS-CoV-2. In most cases, patients were from Teresina (67.62%), of brown race/ethnicity (52.67%), female (79.00%), and the majority were not healthcare professionals (54.27%). The most common age of patients, with the original data, was 33 years. After data correction, the most common age was 28 years. The majority of these cases were not severe (96.44%), and the majority of cases were associated with the first dose of the Covid-19-Covishield-Oxford/AstraZeneca vaccine (43.18%).CONCLUSION: Thus, it is concluded from the partial analysis of the results that headache is the most common adverse event after vaccination against SARS-CoV-2. The profile of patients with the most notifications was brown women aged 30 to 40 years who received the first dose of the Covid-19-Covishield-Oxford/AstraZeneca vaccine. Regarding the severity of events, the vast majority were considered non-severe, and no deaths were mentioned, demonstrating the safety of immunobiologicals.

FUNDAMENTO: Em 2020, foram aprovadas as primeiras vacinas, segundo a OMS. No entanto, surgiram especulações quanto à sua eficácia e eventos adversos pós-vacinais (EAPV). OBJETIVO: Avaliar a prevalência de cefaleia como EAPV da vacina SARSCoV-2 no Piauí, Brasil. MÉTODOS: Trata-se de um estudo quantitativo, observacional, transversal e de prevalência. Os dados foram fornecidos pelo Sistema de Informação de Eventos Adversos Pós-Vacinação (SI-AEFV), dos casos notificados no período de janeiro a setembro de 2021. Os dados foram analisados ​​e a pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da UFPI. RESULTADOS: Foram analisados ​​2.008 casos. Cefaleia foi relatada em 752 casos (27,99%) como EAPV após vacinação contra SARS-CoV-2. Na maioria dos casos, os pacientes eram procedentes de Teresina (67,62%), de raça/etnia parda (52,67%), do sexo feminino (79,00%) e a maioria não era profissional de saúde (54,27%). A idade mais comum dos pacientes, com os dados originais, era de 33 anos. Após correção dos dados, a idade mais comum foi 28 anos. A maioria desses casos não foi grave (96,44%), e a maioria dos casos esteve associada à primeira dose da vacina Covid-19-Covishield-Oxford/AstraZeneca (43,18%).CONCLUSÃO: Assim, conclui-se a partir da análise parcial dos resultados de que cefaleia é o evento adverso mais comum após vacinação contra SARS-CoV-2. O perfil dos pacientes com mais notificações foi de mulheres pardas com idade entre 30 e 40 anos que receberam a primeira dose da vacina Covid-19-Covishield-Oxford/AstraZeneca. Quanto à gravidade dos eventos, a grande maioria foi considerada não grave e não foram mencionados óbitos, demonstrando a segurança dos imunobiológicos.

¿Se puede humanizar el Servicio de Atención de Pacientes Críticos del Hospital El Cruce? / Is it possible to humanize the Critical Patient Care Service of El Cruce Hospital?

[RESUMEN]. Muchas instituciones sanitarias continúan con un enfoque del modelo biomédico centrando sus acciones en los procedimientos y no en la persona y en su integridad, propiciando la deshumanización de la atención y reduciendo lo humano a lo biológico. Este paradigma ha ido cambiando en el último tiempo. La Organización Mundial de la Salud, OMS define a la salud como: "un estado completo de bienestar físico, mental y social, y no solamente la ausencia de afecciones o enfermedades" (1). La atención humanizada de la salud se centra en la persona, como ser multidisciplinario y único respetando sus valores y su libertad de elección. Realizamos un estudio descriptivo y observacional basado en el registro de intervenciones del área de cuidados humanizados realizadas en el Servicio de Atención del paciente crítico, APC entre enero y septiembre de 2023. Las mismas fueron realizadas luego de la solicitud de interconsultas realizadas por los médicos tratantes del servicio de APC. Durante el período de estudio, se llevaron a cabo un total de 117 intervenciones que reflejan acciones concretas de cuidados humanizados. Estas incluyeron 34 intervenciones en comunicación efectiva, 29 acompañamientos familiares, 22 sesiones de soporte psicoespiritual, 16 tratamientos para el dolor, 11 adecuaciones del esfuerzo terapéutico, 4 cuidados integrales en etapas terminales de la vida y 1 seguimiento del duelo. Estos indicadores sugieren un avance hacia una atención más humanizada al reconocer y abordar las necesidades de pacientes y familias mediante una comunicación empática, lo cual refleja una búsqueda activa de mejora en la calidad de vida en momentos críticos.

[ABSTRACT]. Many health institutions continue with an approach to the biomedical model, focusing their actions on procedures and not on the person and their integrity, promoting the dehumanization of care and reducing the human to the biological. This paradigm has been changing in recent times. The World Health Organization defines health as: "a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity." Humanized health care focuses on the person, as a multidisciplinary and unique being, respecting their values and their freedom of choice. We carried out a descriptive and observational study based on the record of interventions in the humanized care area carried out in the APC between January and September 2023. They were carried out after the request for interconsultations carried out by the treating physicians of the APC service. During the study period, a total of 117 interventions were carried out that reflect concrete actions of humanized care. These included 34 interventions in effective communication, 29 family accompaniment, 22 psychospiritual support sessions, 16 pain treatments, 11 adaptations of the therapeutic effort, 4 comprehensive care in terminal stages of life and 1 grief follow-up. These indicators suggest progress towards more humanized care by recognizing and addressing the needs of patients and families through empathetic communication, which reflects an active search for improvement in quality of life in critical moments.

Prevalência de sífilis e fatores de risco associados em internos do sistema prisional do Piauí / Prevalence of syphilis and associated risk factors in prisoners in the Piauí prison system / Prevalencia de sífilis y factores de riesgo asociados en internos del sistema penitenciario de Piauí

Objetivo: Objetivou-se analisar a prevalência de sífilis e fatores de risco em internos nos presídios do Estado do Piauí, Brasil. Métodos: Estudo epidemiológico, transversal, realizado com 2.131 presidiários. Na estatística inferencial foram aplicados testes de hipóteses, com a utilização de regressão logística. O nível de significância utilizado foi de 5%. Resultados: A prevalência de positividade para sífilis foi de 8,4% (IC95% = 7,3-9,6), sendo 19,5% no sexo feminino e 80,5% no sexo masculino. Na análise bivariada observou-se associação entre a sífilis e as variáveis: sexo, uso de drogas ilícitas, uso de piercings, prática sexual com parceiros do mesmo sexo, uso de drogas antes das relações sexuais e conhecimento sobre a forma de transmissão. No modelo multivariado permaneceu associada apenas o uso de drogas antes das relações sexuais. Conclusão: Faz-se necessário promover articulação entre esferas governamentais e entre gestão da saúde e da justiça, para elaborar estratégias de modo a contemplar a demanda de saúde dos internos do sistema prisional do Estado. (AU)

Objective: The objective was to analyze the prevalence of syphilis and risk factors in inmates in prisons in the State of Piauí, Brazil. Methods: Epidemiological, cross-sectional study carried out with 2,131 inmates. In inferential statistics, hypothesis tests were applied, using logistic regression. The level of significance used was 5%. Results: The prevalence of positivity for syphilis was 8.4% (95% CI = 7.3-9.6), 19.5% in females and 80.5% in males. In the bivariate analysis, an association was observed between syphilis and the variables: sex, use of illicit drugs, use of piercings, sexual practice with partners of the same sex, use of drugs before sexual intercourse and knowledge about the form of transmission. In the multivariate model, only drug use remained associated before sexual intercourse. Conclusion: It is necessary to promote articulation between governmental spheres and between health and justice management, in order to develop strategies in order to contemplate the health demand of inmates in the state prison system. (AU)

Objetivo: Este estudio tuvo como objetivo analizar la prevalencia de sífilis y factores de riesgo en reclusos en cárceles del estado de Piauí, Brasil. Métodos: Estudio epidemiológico transversal realizado con 2.131 internos. En estadística inferencial se aplicaron pruebas de hipótesis mediante regresión logística. El nivel de significancia utilizado fue del 5%. Resultados: La prevalencia de positividad para sífilis fue del 8,4% (IC 95% = 7,3-9,6), siendo 19,5% en mujeres y 80,5% en hombres. En el análisis bivariado se observó asociación entre sífilis y las variables: género, uso de drogas ilícitas, uso de piercings, práctica sexual con parejas del mismo sexo, uso de drogas antes de la relación sexual y conocimiento sobre la forma de transmisión. En el modelo multivariado, solo el consumo de drogas antes de las relaciones sexuales permaneció asociado. Conclusion: Es necesario promover la articulación entre los ámbitos gubernamentales y entre la gestión de la salud y la justicia, a fin de desarrollar estrategias para atender la demanda de salud de los internos del sistema penitenciario estatal. (AU)

Avaliação do potencial de morbimortalidade por COVID-19 em comunidades quilombolas rurais de Goiás, Brasil / Assessment of the potential for morbidity and mortality from COVID-19 in rural quilombola communities in Goiás, Brazil

Objetivo: analisar o potencial de morbimortalidade por COVID-19 em comunidades quilombolas rurais. Métodos: estudo transversal, com 26 comunidades do Estado de Goiás. Utilizou-se o método Analytic Hierarchy Process (AHP) que hierarquiza critérios para estimar o índice de prioridade de morbimortalidade por COVID-19, sendo eles: sexo masculino, idade ≥ 60 anos, diabetes, câncer, hipertensão, tabagismo, dislipidemia e obesidade. Resultados: de 1.672 entrevistados, 52,0% eram homens, 19,0% ≥ 60 anos, 5,5% autor referiram diabetes, 19,6% hipertensão, 9,2% dislipidemia, 1,3% obesidade, 0,4% câncer e 13,9% tabagismo. Houve menor índice de prioridade na Comunidade Engenho 2, e maior em Buracão; sendo: idade ≥ 60 anos em Quilombo do Magalhães; sexo masculino em Kalunga dos Morros; diabetes e hipertensão em Tomás Cardoso; dislipidemia em Almeidas; obesidade em Buracão; câncer em Água Limpa; tabagismo em José de Coleto. Conclusão: houve diferentes potenciais de morbimortalidade por COVID-19, demonstrando qual comunidade apresenta maior/menor prioridade para ações estratégicas para enfrentamento da pandemia.

Objective: to analyze the potential for morbidity and mortality from COVID-19 in rural quilombola communities. Methods:cross-sectional study, with 26 communities in the State of Goiás. The Analytic Hierarchy Process (AHP) method was used, which ranks criteria to estimate the COVID-19 morbidity and mortality priority index, namely: male gender, age ≥ 60 years, diabetes, cancer, hypertension, smoking, dyslipidemia and obesity. Results: among the 1,672 respondents, 52.0% were men, 19.0% ≥ 60 years, 5.5% self-reported diabetes, 19.6% hypertension, 9.2% dyslipidemia, 1.3% obesity, 0.4% cancer and 13.9% smoking. There was a lower priority index in the Engenho 2 community, and higher in the Buracão; where: age ≥ 60 years in the Quilombo do Magalhães; male gender in the Kalunga dos Morros; diabetes and hypertension in the Tomás Cardoso; dyslipidemia in the Almeidas; obesity in the Buracão; cancer in the Água Limpa; smoking in the José de Coleto. Conclusion: there were different potential for morbidity and mortality from COVID-19, demonstrating which community has the highest/lowest priority for strategic actions to face the pandemic.

Blue LED as a new treatment to vaginal stenosis due pelvic radiotherapy: Two case reports.

BACKGROUND: Currently, the advancement cancer treatment technology improves overall survival, however, adverse events are still a challenge for health professional. Genitourinary syndrome of menopause and vaginal stenosis are conditions that impact the quality of life of patients undergoing radiotherapy. We present two such cases in patients with previous cervical and endometrial cancer. These conditions were handled with an innovative method using an energy-based device with blue light emitting diode for concomitant vaginal and vulvar irradiation. Positive impact in clinical findings, cytologic changes, and referred symptoms were documented. CASE SUMMARY: One patient diagnosed with vaginal severe vaginal stenosis with previous cervix cancer treatment and other patient diagnosed with mild stenosis with severe dyspareunia and recent endometrium cancer treatment were considered for vulvovaginal treatment with weekly blue led device and closely evaluated with repeated validated questionnaires and cytological samples. CONCLUSION: This innovative technique showed an improvement in all areas of the examiner's criteria, the cytological criteria, and most bothered symptoms.

Cuidados com o uso de insulinas disponibilizadas pelo sus: subsídios para o controle em diabetes mellitusManagement of insulin available by sus: support to control diabetes mellitus / Management of insulin available by sus: support to control diabetes mellitus / Cuidado en el uso de insulinas proporcionado porsus: subvenciones para el cuidado de diabetes mellitus

RESUMO Objetivo: Descrever os cuidados com o uso de insulinas disponibilizadas pelo SUS e analisar os fatores associados aos cuidados inadequados. Método: Estudo transversal com 113 pessoas com Diabetes Mellitus de um ambulatório de Goiânia-GO. Foram coletados dados em prontuários sobre conservação, preparo e administração de insulina que foram classificados em adequados e inadequados. Resultados: Do total de participantes,58,4% eram mulheres e a média de idade foi 48 anos. Hipertensão arterial foi relatada por 70,8% e 89,0% apresentaram hemoglobina glicada ≥7%. A totalidade dos usuários de insulina realizavam pelo menos um tipo de cuidado inadequado e 62,8% realizavam quatro ou mais. Os mais frequentes foram:conservarem locais não recomendados (46,7%), não aplicar insulina 30 minutos antes da refeição (87,5%), não avaliar presença de grumos no frasco de insulina NPH (71,9%) e não retirar a insulina da geladeira entre 15 e 30 minutos antes da aplicação (88,7%). Não houve diferença estatisticamente significante com as variáveis de exposição analisadas, porém a maior proporção de quatro ou mais cuidados inadequados ocorreu nas mulheres, nos jovens, naqueles com 11 ou mais anos de estudo, tempo de doença superior a 10 anos e, entre os que aplicam insulina uma ou duas vezes ao dia. Conclusão: Houve alta prevalência de cuidados inadequados e grande variabilidade de práticas, reforçando a importância da implementação da linha de cuidados em Diabetes Mellitus em todos os níveis de atenção à saúde.

RESUMEN Objetivo: describirlos cuidados con el uso de insulinas proporcionados por el Sistema Único de Salud (SUS) y analizar los factores asociados a los cuidados inadecuados. Método: estudio transversal con 113 personas con Diabetes Mellitus de un ambulatorio de Goiânia-GO-Brasil. Fueron recolectados datos en registros médicos sobre conservación, preparación y administración de insulina que fueron clasificados en adecuados e inadecuados. Resultados: del total de participantes, 58,4% era mujeres y el promedio de edad fue 48 años. La hipertensión arterial fue relatada por 70,8%;y 89,0% presentaron hemoglobina glicada ≥7%. La totalidad de los usuarios de insulina realizaban por lo menos un tipo de cuidado inadecuado y 62,8% realizaban cuatro o más. Los más frecuentes fueron: conservar en locales no recomendables (46,7%), no aplicar insulina 30 minutos antes de la comida (87,5%), no evaluar presencia de grumos en el envase de insulina NPH (71,9%) y no sacar la insulina de la heladera entre 15 y 30 minutos antes de la aplicación (88,7%). No hubo diferencia estadísticamente significante con las variables de exposición analizadas, perola mayor proporción de cuatro o más cuidados inadecuados ocurrió entre las mujeres, en los jóvenes, en aquellos con 11 o más años de estudio, tiempo de enfermedad superior a 10 años y, entre los que aplican insulina una o dos veces al día. Conclusión: hubo alta prevalencia de cuidados inadecuados y gran variabilidad de prácticas, reforzando la importancia de la implementación de la línea de cuidados en Diabetes Mellitus en todos los niveles de atención a la salud.

ABSTRACT Objective: To describe management practices of insulin provided by the SUS and analyze the factors associated with insulin management mistakes. Method: Cross-sectional study addressing 113 individuals with Diabetes Mellitus from an outpatient clinic in Goiânia, GO, Brazil. Data concerning insulin storage, preparation, and administration were collected from the patients' medical records and classified as appropriate or inappropriate. Results: 58.4% of participants were women aged 48 years old on average. Hypertension was reported by 70.8%, and glycated hemoglobin was ≥7% in 89.0%. All the patients made at least one insulin management mistake, and 62.8% made four or more mistakes. The most frequent mistakes were: storing insulin in non-recommended places (46.7%), not injecting insulin 30 minutes before meals (87.5%), not checking for the presence of lumps in the NPH insulin vial (71.9%), and not removing the insulin from the refrigerator between 15 and 30 minutes before injection (88.7%). No significant statistical differences were found among the exposure variables, though women, young individuals, those with 11 or more years of schooling, having the disease for more than ten years, and injecting insulin once or twice a day, more frequently made four or more management mistakes. Conclusion: A high prevalence of insulin management mistakes and considerable variability of practices were identified, reinforcing the importance of implementing a DM line of care at all healthcare system levels.

Laminin-Inspired Cell-Instructive Microenvironments for Neural Stem Cells.

Laminin is a heterotrimeric glycoprotein with a key role in the formation and maintenance of the basement membrane architecture and properties, as well as on the modulation of several biological functions, including cell adhesion, migration, differentiation and matrix-mediated signaling. In the central nervous system (CNS), laminin is differentially expressed during development and homeostasis, with an impact on the modulation of cell function and fate. Within neurogenic niches, laminin is one of the most important and well described extracellular matrix (ECM) proteins. Specifically, efforts have been made to understand laminin assembly, domain architecture, and interaction of its different bioactive domains with cell surface receptors, soluble signaling molecules, and ECM proteins, to gain insight into the role of this ECM protein and its receptors on the modulation of neurogenesis, both in homeostasis and during repair. This is also expected to provide a rational basis for the design of biomaterial-based matrices mirroring the biological properties of the basement membrane of neural stem cell niches, for application in neural tissue repair and cell transplantation. This review provides a general overview of laminin structure and domain architecture, as well as the main biological functions mediated by this heterotrimeric glycoprotein. The expression and distribution of laminin in the CNS and, more specifically, its role within adult neural stem cell niches is summarized. Additionally, a detailed overview on the use of full-length laminin and laminin derived peptide/recombinant laminin fragments for the development of hydrogels for mimicking the neurogenic niche microenvironment is given. Finally, the main challenges associated with the development of laminin-inspired hydrogels and the hurdles to overcome for these to progress from bench to bedside are discussed.

Criação e autoria nas culturas tradicionais desde a Teoria Histórico-Cultural / Creation and authorship in the traditional cultures from Historical-Cultural Theory

As expressões culturais tradicionais sofrem constante subalternização a partir da organização eurocêntrica e colonial, que as deslegitima em seus saberes, cosmologias e modos de ser e viver. O não enquadramento na noção hegemônica de autoria individual nas normas de propriedade intelectual e direitos autorais é uma das formas com que esta subalternização acontece. O entendimento hegemônico de criação é pautado pela ideia moderna de indivíduo. Entretanto, os processos de criação nas expressões culturais tradicionais são coletivos e coincidem com seus processos educativos. O objetivo deste trabalho é propor, a partir da teoria histórico-cultural de Vigotski, um outro olhar para os processos de criação, sob a perspectiva de que pessoa e meio social formam uma unidade indivisível. O texto apresentado é parte de tese de doutorado em educação, de caráter teórico, e concentra suas discussões nas assimetrias entre a autoria individual e o caráter coletivo do ato criador. Conclui-se que não basta a revisão dos mecanismos legais de proteção autoral, mas é necessária uma inversão na lógica hegemônica que embasa tais instrumentos. Propõe-se como caminho um outro entendimento de criação e educação, que reconheça a expressão autêntica das pessoas detentoras de expressões culturais tradicionais.(AU)

The traditional cultural expressions are constantly subalternized by the colonialism and eurocentrism, that delegitimizes their knowledges, cosmologies and ways of being and living. One of this subalternizing practices is the impossibility of claiming intellectual property rights and copyrights, once these laws are based on the hegemonic idea of individual authorship. The hegemonic understanding of creation comes from the modern idea of individual. The objective of this paper is to propose, through the cultural-historical theory of Vigotski, a different approach of the creation process, outlining the perspective that a person and the social medium are an indivisible unity. The paper is a fragment of a theoretical doctoral thesis in Education, and focuses the discussion on the asymmetries between the individual authorship and the collective aspect of the creation act. It concludes that the review of laws is not enough, but there's the necessity of inverting the logic of the hegemonic paradigm. The text proposes another way to understand creation and education, one that recognizes the authentic expression of the traditional cultural expression's holders.(AU)

Engineering hydrogels with affinity-bound laminin as 3D neural stem cell culture systems.

Laminin incorporation into biological or synthetic hydrogels has been explored to recapitulate the dynamic nature and biological complexity of neural stem cell (NSC) niches. However, the strategies currently explored for laminin immobilization within three-dimensional (3D) matrices do not address a critical aspect influencing cell-matrix interactions, which is the control over laminin conformation and orientation upon immobilization. This is a key feature for the preservation of the protein bioactivity. In this work, we explored an affinity-based approach to mediate the site-selective immobilization of laminin into a degradable synthetic hydrogel. Specifically, a four-arm maleimide terminated poly(ethylene glycol) (PEG-4MAL) macromer was functionalized with a mono-PEGylated recombinant human N-terminal agrin (NtA) domain, to promote high affinity binding of laminin. Different NtA concentrations (10, 50 and 100 µM) were used to investigate the impact of NtA density on laminin incorporation, hydrogel biophysical properties, and biological outcome. Laminin was efficiently incorporated for all the conditions tested (laminin incorporation >95%), and the developed hydrogels revealed mechanical properties (average storage modulus (G') ranging from 187 to 256 Pa) within the values preferred for NSC proliferation and neurite branching and extension. Affinity-bound laminin PEG-4MAL hydrogels better preserve laminin bioactivity, compared to unmodified hydrogels and hydrogels containing physically entrapped laminin, this effect being dependent on NtA concentration. This was evidenced by the 10 µM NtA-functionalized PEG-4MAL gels incorporating laminin that support enhanced human NSC proliferation and neurite extension, compared to the latter. Overall, this work highlights the potential of the proposed engineered matrices to be used as defined 3D platforms for the establishment of artificial NSC niches and as extracellular matrix-mimetic microenvironments to support human NSC transplantation.

Assessment of the non-surgical treatment of patients with rectal cancer who underwent neoadjuvant treatment with chemotherapy and radiotherapy at the oncology department / Avaliação do tratamento não cirúrgico de pacientes com câncer de reto submetido ao tratamento neoadjuvante com quimioterapia e radioterapia no serviço de oncologia

ABSTRACT Objective: To describe the partial results of a study in patients with rectal cancer who underwent neoadjuvant treatment with chemotherapy and radiotherapy regarding the rate of complete clinical response, disease-free survival, anorectal function, and quality of life. Material and methods: This was a prospective study from June 2015 to June 2018, in patients with low- or mid-rectum adenocarcinoma and clinical stage II or III, treated with radiotherapy and chemotherapy (IMRT 54 Gy for six weeks) concomitant with 5-fluorouracil (5-FU) 380 mg/m2 and folinic acid (LV) 20 mg/m2 for five days in the first and fifth weeks and two cycles after radiotherapy (5-FU 400 mg/m2 and LV 20 mg/m2) every 28 days. After the treatment, clinical examination, rectosigmoidoscopy, pelvic magnetic resonance imaging, chest and upper abdomen computed tomography, and CEA testing were performed. Resection surgery was performed in those with incomplete clinical response (iCR). Those with complete clinical response (cCR) are under observation (wait-and-see policy). Manometry and scintigraphic function and quality of life scales were collected before treatment and at 30 and 90 days after the end of treatment. Results: As of June 2018, 11 patients were recruited. One was excluded from the analysis for presenting severe toxicity, suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency, after the first chemotherapy cycle. All others completed the treatment. Two patients presented toxicity grade 3/4 related to chemotherapy and had their doses reduced. Seven patients (70%) presented iRC; three underwent rectosigmoidectomy, and the anatomopathological evaluation indicated complete pathological response in two cases (28.5%). Three (30%) presented cCR and did not present evidence of disease after a mean follow-up of 19 months. Patients presented improvement of anorectal function and quality of life. Conclusions: Advances in the neoadjuvant treatment of rectal tumors contributed to better rates of complete pathological responses. New paradigms promote an increase in the complete clinical response rates, which would allow organ preservation and consequent reduction of surgical morbidity.

RESUMO Objetivo: Descrever os resultados parciais de estudo em pacientes com câncer de reto submetidos a tratamento neoadjuvante com quimioterapia e radioterapia quanto à taxa resposta clínica completa, sobrevida livre de doença, função anorretal e qualidade de vida. Material e métodos: Estudo prospectivo desde junho 2015 até junho de 2018, em paciente com adenocarcinoma de reto baixo ou médio e estadio clínico II ou III tratados com RT/QT (IMRT 54 Gy em 6 semanas) concomitante a 5-Fuorouracil (5-FU) 380 mg/m2 e ácido folínico (LV) 20 mg/m2 por 5 dias nas primeira e quinta semanas e dois ciclos após RT (5-FU 400 mg/m2 e LV 20 mg/m2) a cada 28 dias. Após o tratamento, realizou-se exame clínico, retossigmoidoscopia, RNM de pelve, TC de tórax e abdômen superior e dosagem de CEA. Naqueles com Resposta Clínica Incompleta (iRC) procedeu-se à cirurgia de ressecção. Aqueles com Resposta Completa (cRC) estão em observação (wait and see policy). Manometria e escalas de função esfincteriana e qualidade de vida foram obtidas antes e após 30 e 90 dias do término do tratamento. Resultados: Até junho de 2018, recrutaram-se 11 pacientes. Um foi excluído da análise, pois apresentou toxicidade severa sugestiva de deficiência de DPD após o primeiro ciclo de QT. Todos os demais concluíram o tratamento. Toxicidades graus 3/4 relacionadas à QT ocorreram dois pacientes, reduzindo-se sua dose. Sete (70%) apresentaram iRC, submetendo três à retossigmoidectomia cuja avaliação anatomopatológica evidenciou Resposta Completa (pRC) em dois casos (28,5%). Três (30%) apresentaram cRC e estão sem evidência de doença com seguimento médio de 19 meses. Houve melhora da função anorretal e da qualidade de vida. Conclusões: Avanços no tratamento neoadjuvante dos tumores de reto contribuíram para melhores taxas de pRC. Novos paradigmas promovem crescentes índices de cRC, o que possibilitaria a preservação do órgão e consequente redução da morbidade cirúrgica.

Fullerene (C60) particle size implications in neurotoxicity following infusion into the hippocampi of Wistar rats.

The buckminsterfullerene (C60) is considered as a relevant candidate for drug and gene delivery to the brain, once it has the ability to cross the blood-brain barrier. However, the biological implications of this nanomaterial are not fully understood, and its safety for intracerebral delivery is still debatable. In this study, we investigated if C60 particle size could alter its biological effects. For this, two aqueous C60 suspensions were used with maximum particle size up to 200nm and 450nm. The suspensions were injected in the hippocampus, the main brain structure involved in memory processing and spatial localization. In order to assess spatial learning, male Wistar rats were tested in Morris water maze, and the hippocampal BDNF protein levels and gene expression were analyzed. Animals treated with C60 up to 450nm demonstrated impaired spatial memory with a significant decrease in BDNF protein levels and gene expression. However, an enhanced antioxidant capacity was observed in both C60 treatments. A decrease in reactive oxygen species levels was observed in the treatments with suspensions containing particles measuring with up to 450nm. Thiobarbituric acid reactive substances, glutamate cysteine ligase, and glutathione levels showed no alterations among the different treatments. In conclusion, different particle sizes of the same nanomaterial can lead to different behavioral outcomes and biochemical parameters in brain tissue.

Implications of PEGylation of Carbon Nanotubes for Central Nervous System Bioavailability.

BACKGROUND AND OBJECTIVE: In this mini-review, we have compiled the most recent and comparable information to shed light on the action of PEGylation in the biodistribution of carbon nanotubes (CNT) in the central nervous system (CNS). It is well known that due to the complexity of the CNS and the severity of the outcome following changes in this system, this is one of the areas where there are more investments in research to develop new technologies and approaches for more effective and less invasive treatments. The CNS is highly protected against toxic and invasive microorganisms thanks to the blood brain barrier (BBB), but this protection also prevents the passage of potentially beneficial molecules for the treatment of neurological disorders. Nanotechnology attempts to develop nanocompounds that are biocompatible and non-immunogenic, and that are able to cross the BBB in therapeutic amounts without causing damage and to diffuse through nerve tissue. These compounds should also be cleared and biodistributed properly, being capable of performing drug delivery exclusively for CNS pathologies, such as neurodegenerative diseases (Parkinson's and Alzheimer's) and brain tumors. CONCLUSION: In this way, this review focuses on CNT PEGylation, aiming to help in the development of viable and effective nanomedicines for neuroscience applications.

Fibrin functionalization with synthetic adhesive ligands interacting with α6ß1 integrin receptor enhance neurite outgrowth of embryonic stem cell-derived neural stem/progenitors.

To enhance fibrin hydrogel affinity towards pluripotent stem cell-derived neural stem/progenitor cells (NSPCs) and its capacity to support NSPC migration and neurite extension, we explored the tethering of synthetic peptides engaging integrin α6ß1, a cell receptor enriched in NSPCs. Six α6ß1 integrin ligands were tested for their ability to support integrin α6ß1-mediated adhesion of embryonic stem cell-derived NSPCs (ES-NSPs) and sustain ES-NSPC viability, migration, and neuronal differentiation. Due to their better performance, peptides T1, HYD1, and A5G81 were immobilized into fibrin and functionalized gels characterized in terms of peptide binding efficiency, structure and viscoelastic properties. Tethering of T1 or HYD1 successfully enhanced cell outgrowth from ES-NSPC neurospheres (up to 2.4-fold increase), which exhibited a biphasic response to peptide concentration. Inhibition assays evidenced the involvement of α6ß1 and α3ß1 integrins in mediating radial outgrowth on T1-/HYD1-functionalized gels. Fibrin functionalization also promoted neurite extension of single ES-NSPCs in fibrin, without affecting cell proliferation and neuronal differentiation. Finally, HYD1-functionalized gels were found to provide a permissive environment for axonal regeneration, leading up to a 2.0-fold increase in neurite extension from rat dorsal root ganglia explants as compared to unmodified fibrin, and to significant improved locomotor function after spinal cord injury (complete transection), along with a trend toward a higher area positive for growth associated protein 43 (marker for axonal growth cone formation). Our results suggest that conjugation of α6ß1 integrin-binding motifs is of interest to increase the biofunctionality of hydrogels used in 3D platforms for ES-NSPC culture and potentially, in matrix-assisted ES-NSPC transplantation. STATEMENT OF SIGNIFICANCE: Impact statement: The transplantation of NSPCs derived from pluripotent stem cells holds much promise for the treatment of central nervous system disorders. Moreover, the combinatorial use of biodegradable hydrogels with NSPCs was shown to contribute to the establishment of a more permissive environment for survival and integration of transplanted cells. In this study, fibrin hydrogels functionalized with a synthetic peptide engaging integrin α6ß1 (HYD1) were shown to promote neurite extension of ES-NSPCs, which is fundamental for the formation of functional neuronal relay circuits after NSPC transplantation. Notably, HYD1-functionalized fibrin per se led to enhanced axonal growth ex vivo and to an improvement in locomotor function after implantation in a rat model of spinal cord injury. Conjugation of α6ß1 integrin-binding motifs may therefore be of interest to confer bioactivity to NSPC hydrogel vehicles.

Behavioral alterations induced by repeated saxitoxin exposure in drinking water

Background: Blooms of the saxitoxin-producing cyanobacterium Cylindrospermopsis raciborskii have been contaminating drinking water reservoirs in Brazil for many years. Although acute effects of saxitoxin intoxication are well known, chronic deleterious outcomes caused by repeated saxitoxin exposure still require further investigation. The aim of the present work is to investigate the effects of consumption of drinking water contaminated with C. raciborskii for 30 days on learning and memory processes in rats. Methods: The effects of saxitoxin (3 or 9 µg/L STX equivalents) or cyanobacteria on behavior was determined using the open field habituation task, elevated plus maze anxiety model task, inhibitory avoidance task, and referential Morris water maze task. Results: No effects of saxitoxin consumption was observed on anxiety and motor exploratory parameters in the elevated plus maze and open field habituation tasks, respectively. However, groups treated with 9 µg/L STX equivalents displayed a decreased memory performance in the inhibitory avoidance and Morris water maze tasks. Conclusions: These results suggest an amnesic effect of saxitoxin on aversive and spatial memories.(AU)

Behavioral alterations induced by repeated saxitoxin exposure in drinking water

Blooms of the saxitoxin-producing cyanobacterium Cylindrospermopsis raciborskii have been contaminating drinking water reservoirs in Brazil for many years. Although acute effects of saxitoxin intoxication are well known, chronic deleterious outcomes caused by repeated saxitoxin exposure still require further investigation. The aim of the present work is to investigate the effects of consumption of drinking water contaminated with C. raciborskii for 30 days on learning and memory processes in rats. Methods The effects of saxitoxin (3 or 9 g/L STX equivalents) or cyanobacteria on behavior was determined using the open field habituation task, elevated plus maze anxiety model task, inhibitory avoidance task, and referential Morris water maze task. Results No effects of saxitoxin consumption was observed on anxiety and motor exploratory parameters in the elevated plus maze and open field habituation tasks, respectively. However, groups treated with 9 g/L STX equivalents displayed a decreased memory performance in the inhibitory avoidance and Morris water maze tasks. Conclusions These results suggest an amnesic effect of saxitoxin on aversive and spatial memories.

Exposure to methylphenidate during infancy and adolescence in non-human animals and sensitization to abuse of psychostimulants later in life: a systematic review / Exposição a metilfenidato na infância e adolescência em modelos não humanos e sensibilidade ao abuso de drogas psicoestimulantes na vida adulta: revisão sistemática

Introduction:Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric pathology that has an important prevalence among young people and is difficult to diagnose. It is usually treated with methylphenidate, a psychostimulant with a mechanism of action similar to that of cocaine. Previous studies show that repeated use of psychostimulants during childhood or adolescence may sensitize subjects, making them more prone to later abuse of psychostimulant drugs such as cocaine and methamphetamine.Objective: To review experimental studies in non-human models (rodents and monkeys) treated with methylphenidate during infancy or adolescence and tested for reinforcing effects on psychostimulant drugs in adulthood.Method: Systematic collection of data was performed on four databases (Web of Knowledge, PsycARTICLE, PubMed and SciELO). The initial search identified 202 articles published from 2009 to 2014, which were screened for eligibility. Seven articles met the inclusion criteria and were reviewed in this study.Results: The findings indicate that early exposure to methylphenidate has an effect on an ADHD animal model, specifically, on spontaneously hypertensive strain rats, especially those tested using the self-administration paradigm.Conclusion:Future studies should prioritize the spontaneously hypertensive rat strain - an animal model of ADHD. Experimental designs comparing different behavioral paradigms and modes of administration using this strain could lead to improved understanding of the effects of exposure to methylphenidate during childhood and adolescence.

Introdução: O transtorno de déficit de atenção e hiperatividade (TDAH) é uma patologia neuropsiquiátrica de difícil diagnóstico e de relevante prevalência entre pessoas jovens. É comumente tratada com metilfenidato, uma substância psicoestimulante com mecanismo de ação similar ao da cocaína. Estudos prévios demonstram que o uso contínuo de fármacos estimulantes na infância ou adolescência pode sensibilizar o sujeito para o subsequente abuso de drogas psicoestimulantes, como cocaína e metanfetamina.Objetivo:Revisar estudos experimentais em modelos não humanos (roedores e macacos) tratados com metilfenidato na infância ou na adolescência e testados para os efeitos reforçadores de drogas psicoestimulantes na vida adulta.Método: A coleta sistemática dos dados foi realizada em quatro bases de dados (Web of Knowledge, PsycARTICLE, PubMed e SciELO). Na busca inicial, 202 artigos publicados entre 2009 e 2014 foram triados. Destes, sete preencheram os critérios de inclusão e foram revisados neste estudo.Resultados:Os dados indicam um efeito da pré-exposição ao metilfenidato sobre o TDAH em animais adolescentes da linhagem do rato espontaneamente hipertensivo (spontaneously hypertensive strain, SHR). Esse efeito foi encontrado, sobretudo, nos estudos que utilizaram o paradigma de autoadministração.Conclusão: Estudos futuros devem priorizar a linhagem dos SHR - modelo animal do TDAH. Delineamentos que comparem diferentes paradigmas comportamentais e formas de administração utilizando essa linhagem podem prover uma melhor compreensão do efeito da exposição ao metilfenidato na infância e adolescência.

Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the hippocampus.

Biomimetic synthetic self-assembled hydrogels for cell transplantation.

The development of three-dimensional matrices capable of recapitulating the main features of native extracellular matrix and contribute for the establishment of a favorable microenvironment for cell behavior and fate is expected to circumvent some of the main limitations of cell-based therapies. In this context, self-assembly has emerged as a promising strategy to engineer cell-compatible hydrogels. A wide number of synthetically-derived biopolymers, such as proteins, peptides and DNA/RNA, with intrinsic ability to self-assemble into well-defined nanofibrous structures, are being explored. The resulting hydrogels, in addition to closely resembling the architecture of native cellular microenvironments, present a versatile and dynamic behavior that allows them to be designed to undergo sol-to-gel transition in response to exogenous stimulus. This review presents an overview on the state-of-the-art of the different strategies being explored for the development of injectable synthetic self-assembled hydrogels for cell transplantation and/or recruitment of endogenous cells, with an emphasis on their biological performance, both in vitro and in vivo. Systems based on peptides are the most widely explored and have already generated promising results in pre-clinical in vivo studies involving different repair/regenerative scenarios, including cartilage, bone, nerve and heart. On the other hand, systems based on DNA and hybrid hydrogels are now emerging for application in the biomedical field with high potential. Finally, the main challenges hampering the translation of these systems to the clinic and the issues that need to be addressed for these to progress from bench-to-bedside are discussed.