Mimicking 3D breast tumor-stromal interactions to screen novel cancer therapeutics.

Most of the 3D breast tumor models used in drug screening studies only comprise tumor cells, keeping out other essential cell players of the tumor microenvironment. Tumor-associated macrophages and fibroblasts are frequently correlated with tumor progression and therapy resistance, and targeting these cells at the tumor site has been appointed as a promising therapeutic strategy. However, the translation of new therapies to the clinic has been hampered by the absence of cellular models that more closely mimic the features of in vivo breast tumor microenvironment. Therefore, the development of innovative 3D models able to provide consistent and predictive responses about the in vivo efficacy of novel therapeutics is still an unmet preclinical need. Herein, we have established an in vitro 3D heterotypic spheroid model including MCF-7 breast tumor cells, human mammary fibroblasts and human macrophages. To establish this model, different cell densities have been combined and characterized through the evaluation of the spheroid size and metabolic activity, as well as histological and immunohistochemistry analysis of the 3D multicellular structures. The final optimized 3D model consisted in a multicellular spheroid seeded at the initial density of 5000 cells and cell ratio of 1:2:1 (MCF-7:monocytes:fibroblasts). Our model recapitulates several features of the breast tumor microenvironment, including the formation of a necrotic core, spatial organization, and extracellular matrix production. Further, it was validated as a platform for drug screening studies, using paclitaxel, a currently approved drug for breast cancer treatment, and Gefitinib, a chemotherapeutic approved for lung cancer and in preclinical evaluation for breast cancer. Generally, the impact on the cell viability of the 3D model was less evident than in 2D model, reinforcing the relevance of such complex 3D models in addressing novel treatment approaches. Overall, the use of a 3D heterotypic spheroid of breast cancer could be a valuable tool to predict the therapeutic effect of new treatments for breast cancer patients, by recapitulating key features of the breast cancer microenvironment.

COVID-19 pandemic and the quality of antibiotic use in primary care: an interrupted time-series study.

The coronavirus disease-19 pandemic and the related public health mitigation measures have impacted the transmission of infectious diseases; however, their impact on the use of antibacterials has not yet been extensively evaluated. This study evaluated the impact of the pandemic on the consumption patterns of antibacterials for systemic use in primary care in Portugal. An interrupted time-series analysis was performed using the autoregressive integrated moving average model of the antibacterials dispensed in the community pharmacies in Portugal from 1 January 2016 to 30 June 2022. Monthly rates of absolute consumption (all antibacterials for systemic use, and specifically penicillins; cephalosporins; macrolides, lincosamides, and streptogramins; and quinolones) and the relative consumption of antibacterials (penicillins sensitive to ß-lactamase, penicillin combinations including ß-lactamase inhibitors, third- and fourth-generation cephalosporins, fluoroquinolones, and the ratio of broad- to narrow-spectrum antibacterials) were estimated. Antibiotic consumption was expressed in defined daily doses per 1000 inhabitants per day (DID). In Portugal, the consumption of antibacterials (J01) declined sharply immediately after the beginning of the pandemic, having a significant reduction of >5 DID (P < .0001). A similar, short-term impact was found for penicillins (-2.920 DID; P < .0001); cephalosporins (-0.428 DID; P < .0001); macrolides, lincosamides, and streptogramins (-0.681 DID; P = .0021); and quinolones (-0.320 DID; P < .0001). A long-term increase was found for cephalosporins (+0.019 DID per month; P < .0001). Relative consumption changes were only found for third- and fourth-generation cephalosporins (0.0734%). Our study suggests that the coronavirus disease-19 pandemic may have resulted in a decrease in antibiotic use, with no significant changes in the relative dispense. Uncertainties regarding the long-term effects of the pandemic and its impact on the rates of resistance remain.

Reprogramming of tumor-associated macrophages by polyaniline-coated iron oxide nanoparticles applied to treatment of breast cancer.

Breast cancer is the most commonly diagnosed type of cancer among the female population worldwide. It is a disease with a high incidence and geographic distribution that negatively impacts global public health and deleteriously affect the quality of life of cancer patients. Among the new approaches, cancer immunotherapy is the most promising trend in oncology by stimulating the host's own immune system to efficiently destroy cancer cells. Recent evidence has indicated that iron oxide nanoparticles can promote the reprograming of M2 into M1 macrophages with anti-tumor effects in the tumor microenvironment. Thus, the aim of the present work was to evaluate the ability of polyaniline-coated maghemite (Pani/γ-Fe2O3) nanoparticles to modulate human macrophages in 2D monolayers and 3D multicellular breast cancer models. It was observed that Pani/γ-Fe2O3 NPs re-educated IL-10-stimulated macrophages towards a pro-inflammatory profile, decreasing the proportion of CD163+ and increasing the CD86+ proportion in 2D models. NPs were successfully taken-up by macrophages presented in the 3D model and were also able to induce an increasing in their CD86+ proportion in triple MCTs model. Overall, our findings open new perspectives on the use of Pani/γ-Fe2O3 NPs as an immunomodulatory therapy for macrophage reprogramming towards an anti-tumor M1 phenotype, providing a new tool for breast cancer immunotherapies.

Cognitive Foraging Enrichment (but Not Non-Cognitive Enrichment) Improved Several Longer-Term Welfare Indicators in Bottlenose Dolphins.

Bottlenose dolphins are the most common cetacean kept globally in zoos and aquaria (hereafter zoos), and are gregarious animals with a mostly opportunistic, generalist feeding strategy in the wild. In zoos, they have limited to no opportunities to express natural foraging behaviours as they receive their daily food ration of dead fish in a series of training sessions. Enrichment provision has increased in recent years, but items are still predominantly simple and floating in nature, and do not always target the animals' problem-solving or food-acquisition behaviours. These discrepancies run concurrently with the intense debate about dolphin welfare in zoos and how to improve it. The current study used a within-subject design on 11 bottlenose dolphins at Kolmårdens Djurpark and measured how several welfare indicators differed between two treatments of "cognitive" and "non-cognitive" food-based enrichment. The treatments were provided on an alternating basis for eight consecutive weeks: during cognitive enrichment weeks, the animals received items which stimulated their problem-solving and foraging behaviours, and during non-cognitive enrichment weeks, they received simple items paired with fish (to eliminate bias due to food value). Data were taken related to several multidisciplinary welfare parameters during enrichment provision and training sessions, and to activity budget behaviours throughout the week. During the cognitive as opposed to non-cognitive enrichment weeks, the dolphins engaged more with the enrichment, were more motivated to participate in training sessions and performed less anticipatory and stereotypic behaviours, suggesting that cognitive enrichment improved several indicators of bottlenose dolphin welfare. Valuable lines of further investigation would be to understand how individual differences and different types of cognitive enrichment impact potential welfare benefits. Our results suggest that enrichment items promoting cognitive foraging behaviours may improve dolphin welfare, and therefore zoos might prioritise giving cognitive enrichment to this species as well as considering the same for other species with similar cognitive skills and foraging ecologies.

Impact of COVID-19 on a paediatric emergency service.

COVID-19 has significantly affected the use of health care worldwide and, consequently, admissions to hospital emergency services. The aim of this study is to describe the change of the activity of a Paediatric Emergency Service (PES) of a tertiary hospital during the pandemic. A retrospective cohort study with analysis of visits to the PES from March 30 to June 30, 2020, and comparison with homologous periods in the previous 3 years (2017-2019).A total of 53,883 episodes were analysed, with a median age of 5.8 years, and 53% were boys. In 2020, there was a 60% reduction in the number of admissions (p < 0.001). There was a significant increase in referral by the public medical advice phone line of the National Health Service (NHS) (18.5% vs 5.4%) and Emergency Medical Services (EMS) (5.1% vs 4.2%). Urgent patients decreased (31.2% vs 38.3%), and non-urgent patients increased (7.5% vs 1.7%). There was a significant reduction in school (0.4% vs 7.1%) and sports accidents (0.1% vs 1.2%) and an increase in other accidents (falls, wounds, burns, and dog bites) (12.2% vs 6.3%). Hospitalisation rate was higher (5.7% vs 3.1%, p < 0.001). The infection rate for SARS-CoV-2 was 1.1%, all with mild illness or asymptomatic.Conclusion: The pandemic brought a marked reduction in emergency admissions and a decrease in urgent situations but an increase in accidents, such as falls, wounds, burns, and dog bites. Despite the low infection rate for SARS-CoV-2, there were increased referrals by the phone line of NHS and EMS and a higher admission in the ward. What is Known: • The number of admissions to emergency services significantly decreased during the COVID-19 pandemic, particularly in the paediatric population, whom has a milder disease than adults. • Diseases that justify urgent/emergent hospital admission continue to exist and the eventual delay in seeking health care might lead to a worse prognosis. What is New: • Despite the low rate of SARS-CoV-2 infection in children, there was an increase in referrals by the phone line of the National Health Service and Emergency Medical Services. • The global admission rate to the ward increased but there were no admissions to intensive care or deaths.

Craniometry in Cerdocyon thous (Carnivora, Canidae) / Craneometría en Cerdocyon thous (Carnivora, Canidae)

The objective of this study was to obtain data on craniometric parameters in the crab-eating fox (Cerdocyon thous) and to define the general skull type of this species, analysing whether the craniometric classification of domestic dogs can be applied. Eleven skulls of C. thous were included in the analysis, irrespective of age and sex. The location of nine craniometric points established for craniometry in domestic dogs was determined and based on the distances between these points, 17 craniometric parameters were measured. Those parameters were used to calculate the following six craniometric indices: 53.17 ± 2.54 mm skull index, 2.33 ± 0.08 mm craniofacial index, 59.17 ± 3.57 mm neurocranial index, 125.58 ± 6.63 mm facial index, 37.52 ± 2.65 mm basal index and the index of the foramen magnum 54.47 ± 3.48 mm. According to the analysed indices, the skull shape in C. thous can be classified as mesaticephalic.

El objetivo de este estudio fue obtener datos sobre los parámetros craneométricos del zorro cangrejero (Cerdocyon thous) y definir el tipo general de cráneo de esta especie, analizando si se puede aplicar la clasificación craneométrica de los perros domésticos. Once cráneos de C. thous fueron incluidos en el análisis, independientemente de la edad y el sexo. Se determinó la ubicación de nueve puntos craneométricos establecidos para la craneometría en perros domésticos y, en función de las distancias entre estos puntos, se midieron 17 parámetros craneométricos. Esos parámetros se usaron para calcular los siguientes índices craneométricos: índice craneal de 53,17 ± 2,54 mm, índice craneofacial de 2,33 ± 0,08 mm, índice neurocraneal de 59,17 ± 3,57 mm, índice facial de 125,58 ± 6,63 mm, índice basal de 37,52 ± 2,65 mm y el índice del foramen magnum 54,47 ± 3,48 mm. Según los índices analizados, la forma del cráneo en C. thous se puede clasificar como mesaticefálica.

Avaliação geriátrica ampla como preditor de morbimortalidade nos pacientes oncológicos vulneráveis submetidos ao tratamento quimioterápico / Comprehensive geriatric assessment as a morbimortality predictor in patients vulnerable to the chemotherapy treatment

Objetivos: O objetivo desse estudo foi determinar o valor preditivo da Avaliação Geriátrica Ampla (AGA) em relação à toxicidade e mortalidade nos pacientes oncológicos idosos classificados como vulneráveis, submetidos à quimioterapia. Método: Foi realizado um estudo de coorte prospectivo com coleta de informações extraídas de banco de dados já construído do projeto ÂNCORA e disponível online. Foram construídas tabelas de distribuição de frequência das variáveis estudadas e na análise univariada foi usado o chi-quadrado e Teste de Fisher, quando indicado. Por fim, considerou-se o nível de significância de 5% e todos os testes foram aplicados com 95% de confiança. Resultados: Em uma amostra total de 254 pacientes, o percentual de mortalidade foi de 37% e de intercorrências foi de 46,5%, sendo infecção a mais frequente. Houve associação entre o déficit nutricional e o aumento da mortalidade (p=0,003). Conclusão: Observou-se associação estatística entre o aumento da mortalidade em pacientes vulneráveis que realizaram quimioterapia (p=0,046), quando comparados aos pacientes saudáveis. Os resultados deste estudo reforçam constatações da literatura como o uso da AGA pode ajudar oncologistas e geriatras em suas tomadas de decisão.

Objectives: to determine the predictive value of the Comprehensive geriatric assessment (CGA) regarding toxicity and mortality in elderly cancer patients classified as vulnerable who were submitted to chemotherapy. Method: A prospective cohort study was performed with data gathered from the database already built by the anchor project and available online. Tables of the frequency of distribution of the studied variables were created. The chi-square test was used in the univariate analysis, and the Fisher test when indicated. The level of significance of 5% were considered and all the tests were applied with a confidence of 95%. Results: The frequency of patients classified as vulnerable by CGA was 40.2%, and the mortality rate in the total number of patients was 37%. The association between nutritional status and mortality (p=0.003) was observed, where most of the denuded patients (51.4%) died during follow-up, and most patients (46.5%) had some type of complication. Conclusion: There was an association between the increase in mortality in patients vulnerable to chemotherapy (p=0,046), when compared to healthy patients. The results of this study follow the literature on the use of CGA can help oncologists and geriatricians in their decision making.

Arte e mediação terapêutica: sobre um dispositivo com adolescentes na clínica-escola / Art and therapeutic mediation: about one device with adolescents in the school-clinic / Arte y la mediación terapéutica: sobre un dispositivo con adolescentes en la clinica escuela / Art et médiation thérapeutique: a propos d'un dispositif avec des adolescents dans la clinique-ecole

Pretende-se, no presente artigo, apresentar os resultados da pesquisa/intervenção "Arte e mediação terapêutica: sobre um dispositivo com adolescentes na clínica-escola". Ao longo de vinte e quatro meses, oito adolescentes entre 12 e 18 anos, inscritos nos Serviços de Psicologia Aplicada e de Terapia Ocupacional da Universidade de Fortaleza, foram acompanhados em oficinas semanais de artes plásticas, coordenadas por estagiários dos dois cursos e monitores do curso de Belas Artes. O grupo de jovens apresentava graves impasses no campo da aprendizagem escolar. O trabalho de intervenção objetivou, principalmente, a construção de um dispositivo clínico interdisciplinar, com privilégio da mediação terapêutica da arte, levando em conta as especificidades da problemática adolescente, em especial, aquelas relativas à transferência. Nesse sentido, o dispositivo funcionou inspirado em trabalhos institucionais já conhecidos no campo psicanalítico, como a "prática entre vários". Os resultados apontaram que a transferência, nessa modalidade de intervenção, permite a negociação com algumas formas de movimento transferencial que frequentemente se apresentam na clínica psicanalítica com adolescentes. Simultaneamente, o uso da arte pode ser considerado um mediador terapêutico capaz de respeitar essas particularidades, além de promover estratégias representativas do movimento de separação dos laços primários em direção aos laços de sociabilidade ampliada. Através de uma experiência compartilhada de "re-criação", a travessia do um ao Outro possibilita novas aberturas ao ato de aprender.(AU)

The intention of this article is to present the results of the Research/Intervention called "Art and therapeutic mediation: about a device with adolescents in the school-clinic". During twenty-four months, eight teenagers, between twelve and eighteen years, enrolled in an Applied Psychology Service and Occupational Therapy at the University of Fortaleza, where, weekly, they followed art workshops, coordinated by trainees coming from the two mentioned courses and Fine Arts Course's monitors. The teenager group had, in common, severe difficulties on school education field. The intervention work aimed, primarily, at the construction of an interdisciplinary clinical device, with the privileged therapeutic mediation of art, considering the adolescents' specific problems, especially those related to the transference. The clinical device was inspired by an institutional work on the psychoanalytic field known as "practices shared by many." The results showed that the transference, in this type of intervention, allows trading with some transference's movements that often arise in the adolescents' psychoanalytic treatment. Simultaneously, the use of art can be considered a therapeutic mediator able to respect these particularities and to promote strategies representing the movement of separation from the primary relations towards to sociability enlarged. Through a shared experience of "re-creation," the passage from one to another, enables new openings to the act of learning.(AU)

Pretendese, en el presente artículo, presentar los resultados de la Investigación/Intervención "Arte y mediación terapéutica: sobre un dispositivo con adolescentes en la clínica escuela". A lo largo de veinte cuatro meses, ocho adolescentes entre doce y dieciocho años, inscriptos en los Servicios de Psicología Aplicada y de Terapia Ocupacional de la Universidad de Fortaleza fueron acompañados en talleres semanales de artes, coordinadas por pasantes de los dos cursos y monitores del Curso de Artes. El grupo de jóvenes presentaba, en común, graves callejones en el campo del aprendizaje escolar. El trabajo de intervención objetivó, principalmente, la construcción de un dispositivo clínico interdisciplinar, con privilegio de la mediación terapéutica de la arte, considerándose las particularidades de la problemática adolescente, en especial, a las relativas a la transferencia. En este sentido, el dispositivo funcionó inspirado en trabajos institucionales conocidos en el campo psicoanalítico como la "practica entre varios". Los resultados señalaran que la transferencia, en esta modalidad de intervención entre varios, permite la negociación con algunas formas de movimiento transferencial que, frecuentemente, presentanse en la clínica psicoanalítica con adolescentes. Simultáneamente, la utilización de la arte puede ser considerado un mediador terapéutico capaz de respetar esas particularidades, además de promover estrategias representativas del movimiento de separación de los lazos primarios en dirección a los lazos de sociabilidad ampliada. A través de una experiencia compartida de "re-creación", la travesía del uno al Otro, posibilita nuevas aperturas al acto de aprender.(AU)

Il s'agit, dans cet article, de présenter les résultats de la recherche/intervention intitulée "Art et médiation thérapeuthique": à propos d'un dispositif avec des adolescents dans la Clinique-école". Au long de vingt et quatre mois, huit adolescents agés entre douze et diz-huit ans qui étaient inscrits dans les Services de Psychologie Apliquée et de Thérapie Occupationel de l'Université de Fortaleza, ont été suivis dans le cadre d'ateliers d'arts plastiques, dirigés par des stagiaires des deux cours et d' élèves de la Faculté de Beaux Arts. Le group de jeunes presentait, en commun, des graves difficultés dans le domaine de l'apprentissage scolaire. Le travail d'intervention a eu comme objectif, tout d'abord, la construction d'un dispositif clinique interdisciplinaire, en s'utilisant, de manière privilégiée, de la médiation thérapeutique de l'art, et en prennant en considération les specificités de la problématique adolescent, en particulier, celles concernant le transfert. Dans ce sens, le dispositif a été inspiré dans les travaux institutionnels connus parmi les psychanalystes comme "pratique en plusieurs". Les résultats ont indiqué que le transfert, dans cette modalité d'intervention en plusieurs, permet une négociation avec certaines formes de mouvement du tranfert qui définissent, souvent, la clinique d'adolescents. Au même temps, l'usage de l'art peut être consideré en tant qu'un médiateur thérapeutique capable de respecter ces particularités, et promouvoir des stratégies répresentatives du mouvement de séparation des liens primaires en direction aux liens de sociabilité élargie. La traversée de l'Un à l'Autre, possibilitée par une expérience partagée de "récreation", permet des nouvelles voies à l'act d'apprendre.(AU)

Arte e mediação terapêutica: sobre um dispositivo com adolescentes na clínica-escola / Art and therapeutic mediation: about one device with adolescents in the school-clinic / Arte y la mediación terapéutica: sobre un dispositivo con adolescentes en la clinica escuela / Art et médiation thérapeutique: a propos d'un dispositif avec des adolescents dans la clinique-ecole

Pretende-se, no presente artigo, apresentar os resultados da pesquisa/intervenção "Arte e mediação terapêutica: sobre um dispositivo com adolescentes na clínica-escola". Ao longo de vinte e quatro meses, oito adolescentes entre 12 e 18 anos, inscritos nos Serviços de Psicologia Aplicada e de Terapia Ocupacional da Universidade de Fortaleza, foram acompanhados em oficinas semanais de artes plásticas, coordenadas por estagiários dos dois cursos e monitores do curso de Belas Artes. O grupo de jovens apresentava graves impasses no campo da aprendizagem escolar. O trabalho de intervenção objetivou, principalmente, a construção de um dispositivo clínico interdisciplinar, com privilégio da mediação terapêutica da arte, levando em conta as especificidades da problemática adolescente, em especial, aquelas relativas à transferência. Nesse sentido, o dispositivo funcionou inspirado em trabalhos institucionais já conhecidos no campo psicanalítico, como a "prática entre vários". Os resultados apontaram que a transferência, nessa modalidade de intervenção, permite a negociação com algumas formas de movimento transferencial que frequentemente se apresentam na clínica psicanalítica com adolescentes. Simultaneamente, o uso da arte pode ser considerado um mediador terapêutico capaz de respeitar essas particularidades, além de promover estratégias representativas do movimento de separação dos laços primários em direção aos laços de sociabilidade ampliada. Através de uma experiência compartilhada de "re-criação", a travessia do um ao Outro possibilita novas aberturas ao ato de aprender.

The intention of this article is to present the results of the Research/Intervention called "Art and therapeutic mediation: about a device with adolescents in the school-clinic". During twenty-four months, eight teenagers, between twelve and eighteen years, enrolled in an Applied Psychology Service and Occupational Therapy at the University of Fortaleza, where, weekly, they followed art workshops, coordinated by trainees coming from the two mentioned courses and Fine Arts Course's monitors. The teenager group had, in common, severe difficulties on school education field. The intervention work aimed, primarily, at the construction of an interdisciplinary clinical device, with the privileged therapeutic mediation of art, considering the adolescents' specific problems, especially those related to the transference. The clinical device was inspired by an institutional work on the psychoanalytic field known as "practices shared by many." The results showed that the transference, in this type of intervention, allows trading with some transference's movements that often arise in the adolescents' psychoanalytic treatment. Simultaneously, the use of art can be considered a therapeutic mediator able to respect these particularities and to promote strategies representing the movement of separation from the primary relations towards to sociability enlarged. Through a shared experience of "re-creation," the passage from one to another, enables new openings to the act of learning.

Pretendese, en el presente artículo, presentar los resultados de la Investigación/Intervención "Arte y mediación terapéutica: sobre un dispositivo con adolescentes en la clínica escuela". A lo largo de veinte cuatro meses, ocho adolescentes entre doce y dieciocho años, inscriptos en los Servicios de Psicología Aplicada y de Terapia Ocupacional de la Universidad de Fortaleza fueron acompañados en talleres semanales de artes, coordinadas por pasantes de los dos cursos y monitores del Curso de Artes. El grupo de jóvenes presentaba, en común, graves callejones en el campo del aprendizaje escolar. El trabajo de intervención objetivó, principalmente, la construcción de un dispositivo clínico interdisciplinar, con privilegio de la mediación terapéutica de la arte, considerándose las particularidades de la problemática adolescente, en especial, a las relativas a la transferencia. En este sentido, el dispositivo funcionó inspirado en trabajos institucionales conocidos en el campo psicoanalítico como la "practica entre varios". Los resultados señalaran que la transferencia, en esta modalidad de intervención entre varios, permite la negociación con algunas formas de movimiento transferencial que, frecuentemente, presentanse en la clínica psicoanalítica con adolescentes. Simultáneamente, la utilización de la arte puede ser considerado un mediador terapéutico capaz de respetar esas particularidades, además de promover estrategias representativas del movimiento de separación de los lazos primarios en dirección a los lazos de sociabilidad ampliada. A través de una experiencia compartida de "re-creación", la travesía del uno al Otro, posibilita nuevas aperturas al acto de aprender.

Il s'agit, dans cet article, de présenter les résultats de la recherche/intervention intitulée "Art et médiation thérapeuthique": à propos d'un dispositif avec des adolescents dans la Clinique-école". Au long de vingt et quatre mois, huit adolescents agés entre douze et diz-huit ans qui étaient inscrits dans les Services de Psychologie Apliquée et de Thérapie Occupationel de l'Université de Fortaleza, ont été suivis dans le cadre d'ateliers d'arts plastiques, dirigés par des stagiaires des deux cours et d' élèves de la Faculté de Beaux Arts. Le group de jeunes presentait, en commun, des graves difficultés dans le domaine de l'apprentissage scolaire. Le travail d'intervention a eu comme objectif, tout d'abord, la construction d'un dispositif clinique interdisciplinaire, en s'utilisant, de manière privilégiée, de la médiation thérapeutique de l'art, et en prennant en considération les specificités de la problématique adolescent, en particulier, celles concernant le transfert. Dans ce sens, le dispositif a été inspiré dans les travaux institutionnels connus parmi les psychanalystes comme "pratique en plusieurs". Les résultats ont indiqué que le transfert, dans cette modalité d'intervention en plusieurs, permet une négociation avec certaines formes de mouvement du tranfert qui définissent, souvent, la clinique d'adolescents. Au même temps, l'usage de l'art peut être consideré en tant qu'un médiateur thérapeutique capable de respecter ces particularités, et promouvoir des stratégies répresentatives du mouvement de séparation des liens primaires en direction aux liens de sociabilité élargie. La traversée de l'Un à l'Autre, possibilitée par une expérience partagée de "récreation", permet des nouvelles voies à l'act d'apprendre.

Successful nonmyeloablative allogeneic stem cell transplantation for therapy-related acute myelogenous leukemia in a patient with preexisting visceral fungal infection.

Therapy-related acute myelogenous leukemia (t-AML) is a generally fatal disease with a very poor response to conventional chemotherapy. Allogeneic stem cell transplantation (allo-SCT) has been reported in patients with chemotherapy- responsive t-AML. However its use is limited owing to complications from previous treatments. Nonmyeloablative conditioning provides rapid hematologic engraftment and it is a feasible option for patients who are at increased risk for conventional SCT. There are few data on their use in patients with t-AML. We describe the case of a boy who developed visceral fungal infection with liver abscesses after induction chemotherapy for t-AML. He received allo-SCT with a nonmyeloablative regimen, plus amphotericin B during the transplant procedure. The patient is alive and free of both leukemia and fungal infection 2 years after allo-SCT. Nonmyeloablative allo-SCT may provide durable remission in patients with t-AML, preexisting invasive fungal infections, and a high risk of adverse effects from standard chemotherapy and prolonged cytopenia, without resurgence of the fungal infection.

Loss of vision secondary to obsessive-compulsive disorder: a case report.

OBJECTIVE: To report a rare case of self-inflicted eye injury secondary to obsessive-compulsive disorder (OCD). METHOD: Case report. RESULTS: A 41 year-old patient had significant bilateral visual loss and blunt trauma through touching his ocular cavities due to recurrent doubts regarding their shape and urges to check the format of bones and cartilages. Differential diagnosis with tic disorders is discussed, and the patient's treatment approach is described. CONCLUSION: Although rare, severe clinical complications can occur in OCD.

Prospective trial of mycophenolate mofetil-cyclosporine A prophylaxis for acute GVHD after G-CSF stimulated allogeneic bone marrow transplantation with HLA-identical sibling donors in patients with severe aplastic anemia and hematological malignancies.

The combination of methotrexate and cyclosporine A (MTX-CSA) is the standard regimen for the prevention of graft vs. host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) from HLA-identical siblings. Mycophenolate mofetil and CSA (MMF-CSA) combination has been successfully used for GVHD prophylaxis after non-reduced intensity conditioning (non-RIC) allo-SCT with peripheral blood or non-G-CSF stimulated bone marrow as stem cell source. We report the results of the first prospective trial of the MMF-CSA combination for acute GVHD prophylaxis in 47 patients after non-RIC G-CSF stimulated allo-BMT (G-BMT) from HLA-identical siblings in patients with severe aplastic anemia (SAA) or hematological malignancies. Median age was 28 yr (range, 6-48 yr). Median follow-up was 22 months. The median time to neutrophil and platelets recovery were nine d (range, 8-17) and 16 d (range, 10-28), respectively. Acute GVHD of grade II-IV and chronic GVHD occurred in 51% and 27%, respectively. Overall survival rates at two yr for patients with SAA and hematological malignancies were 87% and 65%, respectively. The event-free survival at two yr for patients with hematological malignancies was 76%. We concluded that MMF-CSA appears equivalent to MTX-CSA for GVHD prophylaxis in patients receiving non-RIC G-BMT from HLA-identical siblings, with a tendency for more rapid neutrophil engraftment.

Prevalence and associated factors for suicidal ideation and behaviors in obsessive-compulsive disorder.

INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) have historically been considered at low risk for suicide, but recent studies are controversial. OBJECTIVE: To study the prevalence of suicidal thoughts and attempts in OCD patients and to compare those with and without suicidality according to demographic and clinical variables. METHODS: Fifty outpatients with primary OCD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) from a Brazilian public university were evaluated. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess OCD severity, the Beck Depression Inventory to evaluate depressive symptoms and the Alcohol Use Disorders Identification Test to assess alcohol problems. RESULTS: All patients had obsessions and compulsions, 64% a chronic fluctuating course and 62% a minimum Y-BOCS score of 16. Half of the patients presented relevant depressive symptoms, but only three had a history of alcohol problems. Seventy percent reported having already thought that life was not worth living, 56% had wished to be dead, 46% had suicidal ideation, 20% had made suicidal plans, and 10% had already attempted suicide. Current suicidal ideation occurred in 14% of the sample and was significantly associated with a Y-BOCS score >16. Previous suicidal thoughts were associated with a Beck Depression Inventory score >19. CONCLUSION: Suicidality has been underestimated in OCD and should be investigated in every patient, so that appropriate preventive measures can be taken.

Low significance of MECP2 mutations as a cause of mental retardation in Brazilian males.

MeCP2 is a protein that selectively binds to methylated cytosines through its methyl-CpG-binding domain (MBD) and connects DNA methylation to transcriptional repression. Mutations in MECP2 gene, located in Xq28, have been reported as being the major cause of Rett syndrome and are also associated with some cases of X-linked mental retardation in both males and females. In this study, we present the first screening in the MECP2 gene in a Brazilian cohort of 239 unrelated males with idiopathic mental retardation. Eight sequence variations were observed in 10 patients: one novel putative pathogenic variant, two never described variants of unknown pathogenic value and five non-pathogenic variations. We conclude that in mentally retarded Brazilian males, non-pathogenic variants in the MECP2 gene are more common than actual pathogenic mutations, and therefore alterations in this gene have a weak relationship with mental retardation in males.

[Prevalence and risk factors of common mental disorders among medical students]. / Prevalência e fatores de risco para transtornos mentais comuns entre estudantes de medicina.

OBJECTIVE: To estimate the prevalence and assess risk factors of common mental disorders among medical students. METHODS: A cross-sectional study was carried out comprising 551 university medical students in the state of São Paulo, Southeastern Brazil. A self-administered questionnaire to collect sociodemographic and course-related data as well as the Self-Reporting Questionnaire were used. Both Chi-square test and logistic regression were used in data analyses. RESULTS: A total of 82.6% of the students enrolled in the course participated in the study. Most of them were women (61%), 60% aged between 20 and 23 years, and 99% were from other cities. The prevalence of common mental disorders was 44.7% and they were independently associated with: difficulty in making friends (OR=2.0), poor self-evaluation of academic performance (OR=1.7), thoughts of dropping out of the medical course (OR=5.0) and perceived lack of emotional support (OR=4.6). Although prevalence of these disorders was associated with the course period in the first analysis, this association was not maintained in the multivariate analysis. CONCLUSIONS: The prevalence of common mental disorders was shown to be high among medical students, associated with variables concerning support networks. Emotionally tense experiences such as dealing with seriously ill patients and peer group formation in the last years of the medical course are potentially strong stressors, especially for those with poor social support. It is suggested that educational institutions should be aware of that and make interventions aiming at treating and caring for the students' distress.