A computational diffusion model to study antibody transport within reconstructed tumor microenvironments.

BACKGROUND: Antibodies revolutionized cancer treatment over the past decades. Despite their successfully application, there are still challenges to overcome to improve efficacy, such as the heterogeneous distribution of antibodies within tumors. Tumor microenvironment features, such as the distribution of tumor and other cell types and the composition of the extracellular matrix may work together to hinder antibodies from reaching the target tumor cells. To understand these interactions, we propose a framework combining in vitro and in silico models. We took advantage of in vitro cancer models previously developed by our group, consisting of tumor cells and fibroblasts co-cultured in 3D within alginate capsules, for reconstruction of tumor microenvironment features. RESULTS: In this work, an experimental-computational framework of antibody transport within alginate capsules was established, assuming a purely diffusive transport, combined with an exponential saturation effect that mimics the saturation of binding sites on the cell surface. Our tumor microenvironment in vitro models were challenged with a fluorescent antibody and its transport recorded using light sheet fluorescence microscopy. Diffusion and saturation parameters of the computational model were adjusted to reproduce the experimental antibody distribution, with root mean square error under 5%. This computational framework is flexible and can simulate different random distributions of tumor microenvironment elements (fibroblasts, cancer cells and collagen fibers) within the capsule. The random distribution algorithm can be tuned to follow the general patterns observed in the experimental models. CONCLUSIONS: We present a computational and microscopy framework to track and simulate antibody transport within the tumor microenvironment that complements the previously established in vitro models platform. This framework paves the way to the development of a valuable tool to study the influence of different components of the tumor microenvironment on antibody transport.

MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model.

OBJECTIVES: Pancreatic cancer (PCa) is treatable by surgery when detected at an early stage. Non-invasive imaging methods able to detect both established tumours and their precursor lesions are needed to select patients for surgery. We investigated here whether pancreatic preneoplasia could be detected prior to the development of invasive cancers in genetically engineered mouse models of PCa using metabolic imaging. DESIGN: The concentrations of alanine and lactate and the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) were measured in extracts prepared from the pancreas of animals at different stages of disease progression; from pancreatitis, through tissue with predominantly low-grade and then high-grade pancreatic intraepithelial neoplasia and then tumour. (13)C magnetic resonance spectroscopic imaging ((13)C-MRSI) was used to measure non-invasively changes in (13)C labelling of alanine and lactate with disease progression, following injection of hyperpolarised [1-(13)C]pyruvate. RESULTS: Progressive decreases in the alanine/lactate concentration ratio and ALT/LDH activity ratio with disease progression were accompanied by a corresponding decrease in the [1-(13)C]alanine/[1-(13)C]lactate signal ratio observed in (13)C-MRSI images of the pancreas. CONCLUSIONS: Metabolic imaging with hyperpolarised [1-(13)C]pyruvate enables detection and monitoring of the progression of PCa precursor lesions. Translation of this MRI technique to the clinic has the potential to improve the management of patients at high risk of developing PCa.

Efficiency of basalt zeolite and Cuban zeolite to adsorb ammonia released from poultry litter.

Confined poultry production is an important livestock activity, which generates large amounts of waste associated with the potential for environmental pollution and ammonia (NH3) emissions. The release of ammonia negatively affects poultry production and decreases the N content of wastes that could be used as soil fertilizers. The objective of this study was to evaluate a low-cost, simple and rapid method to simulate ammonia emissions from poultry litter as well as to quantify the reduction in the ammonia emissions to the environment employing two adsorbent zeolites, a commercial Cuban zeolite (CZ) and a ground basalt Brazilian rock containing zeolite (BZ). The experiments were conducted in a laboratory, in 2012-2013. The zeolites were characterized by X-ray diffraction (XRD), X-ray fluorescence spectrometry (XRF), physical adsorption of N2 (BET) and scanning electron microscopy (SEM). Ammonia released from poultry litter and its simulation from NH4OH solution presented similar capture rates of 7.99 × 10-5 and 7.35 × 10-5 mg/h, respectively. Both zeolites contain SiO2 and Al2O3 as major constituents, with contents of 84% and 12% in the CZ, and 51% and 12% in the BZ, respectively, besides heulandite groups. Their BET surface areas were 89.4 and 11.3 m2 g-1, respectively, and the two zeolites had similar surface morphologies. The zeolites successfully adsorbed the ammonia released, but CZ was more efficient than BZ, since to capture all of the ammonia 5 g of CZ and 20 g of BZ were required. This difference is due to higher values for the superficial area, porosity, CEC and acid site strength of CZ relatively to BZ. The proposed methodology was shown to be an efficient method to simulate and quantify the ammonia released from poultry litter.

Subduction initiation triggered the Caribbean large igneous province.

Subduction provides the primary driving force for plate tectonics. However, the mechanisms leading to the formation of new subduction zones remain debated. An example is the Lesser Antilles Arc in the Atlantic. Previous initiation mechanisms have implied the transmission of subduction from the Pacific Ocean or the impact of a plume head. Here, we use geodynamic models to simulate the evolution of the Caribbean region during the Cretaceous, where the eastern Pacific subduction triggered the formation of a new subduction zone in the Atlantic. The simulations show how the collision of the old Caribbean plateau with the Central America margin lead to the formation of a new Atlantic subduction zone by polarity reversal. The results further show how subduction renewal on the back of the old Caribbean plateau (present-day Central America) resulted in a major mantle flow reorganization that generated a subduction-induced plume consistent with the formation of the Caribbean Large Igneous Province.

Characteristics of offenders deemed not guilty by reason of insanity in Portugal.

In Portugal, offenders found not guilty by reason of insanity (NGRI), may be given a restricted order to a special hospital as an alternative to prison. In European countries there is a recognized need for data concerning this special population. The aim of the present study was to examine the characteristics of all the NGRI subjects (n = 274) detained in the country in a descriptive and retrospective survey conducted in January 2009. Offence committed, demographic factors, diagnosis at admission, background of substance abuse and diagnostic stability were recorded. Schizophrenia was the commonest diagnosis (51.5%). Mean population age was 42.6 years, with only 6.2% women. Homicide was the most common offense (41.2%). A background of substance abuse was found in 42.3% of subjects. There were significant differences in the schizophrenia and mental retardation patient groups when compared individually with the other diagnoses concerning homicide and arson as the offence. Mean duration of inpatient stay did not differ significantly between diagnoses. The findings also point to poor follow-up of the NGRI patients after admission.

The impact of the Lisbon Football Derby on the profile of emergency department admissions.

BACKGROUND: Variations in emergency department admissions have been reported to happen as a result of major sports events. The work presented assessed changes in volume and urgency level of visits to a major Emergency Department in Lisbon during and after the city's football derby. MATERIAL AND METHODS: Volume of attendances and patient urgency level, according to the Manchester Triage System, were retrospectively analyzed for the 2008-2011 period. Data regarding 24-hour periods starting 45 minutes before kick-off was collected, along with data from similar periods on the corresponding weekdays in the previous years, to be used as controls. Data samples were organized according to time frame (during and after the match), urgency level, and paired accordingly. RESULTS: A total of 14 relevant periods (7 match and 7 non-match) were analyzed, corresponding to a total of 5861 admissions. During the match time frame, a 20.6% reduction (p = 0.06) in the total number of attendances was found when compared to non-match days. MTS urgency level sub-analysis only showed a statistically significant reduction (26.5%; p = 0.05) in less urgent admissions (triage levels green-blue). Compared to controls, post-match time frames showed a global increase in admissions (5.6%; p = 0.45), significant only when considering less urgent ones (18.9%; p = 0.05). DISCUSSION: A decrease in the total number of emergency department attendances occurred during the matches, followed by a subsequent increase in the following hours. These variations only reached significance among visits triaged green-blue. CONCLUSION: During major sports events an overall decrease in emergency department admissions seems to take place, especially due to a drop in visits associated with less severe conditions.

IntroduçÉo: Está descrita a ocorrência de variações nas admissões ao serviço de urgência como resultado de eventos desportivos importantes. O estudo que apresentamos avaliou mudanças no volume e tipo de visitas a um serviço de urgência central de Lisboa durante e após o derby futebolístico da cidade.Material e Métodos: Analisámos retrospectivamente o volume de admissões e a categoria de urgência atribuída pela Triagem de Manchester, de 2008 a 2011. Recolhemos dados relativos a períodos de 24 horas com início 45 minutos antes dos jogos, assim como dados relativos a períodos semelhantes nos dias da semana correspondentes dos anos anteriores, para controlo. Organizaram-se os dados por espaços temporais (durante e pós-jogo) e categoria de urgência, após o que se emparelharam.Resultados: Analisaram-se 14 períodos (sete com jogo e sete sem jogo) e um total de 5861 admissões. Durante o jogo verificou-se uma reduçÉo de 20,6% (p = 0,06) no número total de admissões face aos dias controlo. Na sub-análise das categorias da Triagem de Manchester a reduçÉo foi estatisticamente significativa (26,5%; p = 0,05) apenas nas admissões menos urgentes (categorias verdeazul). Comparado com o controlo, o pós-jogo mostrou um aumento global do número de admissões (5,6%; p = 0,45), significativo somente quando consideradas as menos urgentes (18,9%; p = 0,05).DiscussÉo: Durante os jogos o número total de admissões ao serviço de urgência sofreu um decréscimo, ocorrendo nas horas subsequentes um aumento das mesmas. Estas variações só foram significativas nas categorias de triagem verde-azul.ConclusÉo: Durante eventos desportivos importantes parece dar-se uma reduçÉo nas admissões ao serviço de urgência, sobretudo devido a uma diminuiçÉo das visitas associadas a situações menos graves.

Phosphorus fractions in soil after successive crops of Pinus taeda L. without fertilization / Frações de fósforo após cultivos sucessivos de Pinus taeda L. sem fertilização

ABSTRACT: Pinus cultivation without fertilization is a common practice in southern Brazil, which can induce a decline in the availability of phosphorus (P) in the soil. The purpose of this study was to evaluate the changes in phosphorus fractions in a Humic Cambisol subjected to continuous Pinus taeda L. cultivation without fertilization. Two forest stands were evaluated, after 16 years of Pinus cultivation (1st crop) and 49 years (3rd crop), when soil samples were collected (layers 0-10, 10-20, 20-40, 40-60, and 60-80cm) from six trenches per forest. In soil samples, the P contained in organic (Po) and inorganic (Pi) forms was determined by sequential chemical fractionation. Labile inorganic P fractions remained unchanged after the different cultivation periods. However, the labile organic fractions declined from the first to the third cycle (from 70.6 to 39.8mg dm-3 in the 0-10cm layer), indicating that these forms influence the buffering capacity of labile Pi. The moderately labile organic P acted as a P drain, increasing its percentage of the total, from 34.7 to 56.3%, from the first to the third crop. Soil cultivation for 49 years with Pinus taeda resulted in a reduction of the organic P content, indicating that for this soil use, this P form should be used to diagnose P availability and fertilization requirements.

RESUMO: O cultivo de Pinus sem uso de fertilização é uma prática comum no sul do Brasil e pode levar ao declínio da disponibilidade de fósforo (P) no solo. O objetivo deste estudo foi avaliar as modificações nas frações de fósforo em Cambissolo submetido a sucessivos cultivos de Pinus taeda L. sem fertilização. Foram avaliadas duas florestas, com 16 anos de cultivo de Pinus (1o cultivo) e 49 anos (3o cultivo), onde amostras de solo foram coletadas nas camadas de 0-10, 10-20, 20-40, 40-60 e 60-80cm, em seis trincheiras por floresta. Nas amostras de solo foram determinados os teores de P em formas orgânicas (Po) e inorgânicas (Pi) usando esquema de fracionamento químico sequencial. As frações inorgânicas lábeis de P não sofreram alterações com os diferentes tempos de cultivo, no entanto houve declínio das frações orgânicas lábeis do primeiro para o terceiro cultivo, passando de 70,6 para 39,8mg dm-3 na camada de 0-10cm, indicando que essas formas atuam no tamponamento do Pi lábil. O P orgânico moderadamente lábil atuou como um dreno de P, aumentando seu percentual em relação ao total, de 34,7 para 56,3%, do primeiro para o terceiro cultivo. O cultivo do solo por 49 anos com Pinus taeda provoca a diminuição do teor de fósforo orgânico lábil, indicando que para este tipo de uso do solo essa forma de fósforo deveria ser considerada para diagnóstico da disponibilidade de fósforo e necessidade de fertilização.

Effective treatment with clozapine and valproate for refractory schizophrenia-like psychosis after cerebellar hemorrhage.

BACKGROUND: The cerebellum has traditionally been regarded as an organ of motor coordination. However, the importance of the cerebellum in psychiatric disorders, behavior, and cognition is increasingly being recognized. There is no consensus concerning treatment of schizophrenia-like psychosis after cerebellar pathology. Reports describe the use of several antipsychotics, either alone or in combination with antidepressants or lithium. Clozapine is used for the treatment of refractory schizophrenia, but there are no reports of its use in the above-mentioned situation. CASE PRESENTATION: We report the case of a 20-year-old woman who developed a schizophrenia-like psychosis after rupture of arteriovenous malformation at 13 years of age. The psychotic symptoms proved to be resistant to treatment, and several psychopharmacological schemas were tried. The clinical picture only showed consistent improvement with the combined use of clozapine and valproate. CONCLUSIONS: The relationship between chronic psychosis and cerebellar pathology remains poorly understood. Cases like the present one suggest that clozapine and valproate may be used safely and effectively in refractory schizophrenia-like psychosis associated with cerebellar pathology.

Munchausen syndrome mimicking psychiatric disease with concomitant genuine physical illness.

Munchausen syndrome is a disorder in which patients intentionally produce symptoms mimicking physical or psychiatric illnesses with the aim to assume the sick role and to gain medical attention. Once a patient receives a Munchausen syndrome diagnosis every complaint made thence tends to be regarded with scepticism by clinical staff. However, it is possible that a bona fide illness, which might be disregarded, may coexist in these patients. We report a case of MS mimicking psychiatric disease with concomitant genuine acute physical illness. Despite the initial doubts about the veracity of the latter, due to its prompt recognition, treatment was successful.

Acute psychotic episode in a patient with thyrotoxicosis factitia.

Psychotic syndromes in the context of hyperthyroidism are seldom mentioned in medical textbooks and only a few cases have been published. Typically, such cases present as an affective psychosis. Schizophrenia-like psychosis is a rare occurrence in hyperthyroidism and the link between these two conditions is still poorly understood.We report the case of a female patient with a known history of chronic lymphocytic thyroiditis. The patient presented to our emergency department with an acute schizophrenia-like psychosis. Elevated levels of T4 and free T4 were found. These resulted from the patient's voluntary intake of excess levothyroxine as an attempt to lose weight (thyrotoxicosis factitia). Normalisation of thyroid hormone levels and antipsychotic treatment led to prompt remission of the psychosis. Even though the patient stopped the antipsychotics, she remained free of symptoms during the follow-up. Similar cases are briefly reviewed and some of the data from basic research is also considered.

Influencia do solvente, da relação solo/solvente, e da incubação das amostras úmidas na variação do pH de solos Catarinenses / Influence of solvent type, soil/solvent ratio, and undryed sample incubation on pH values of some Brazilian soils

O pH do solo é um dos índices mais importantes na avaliação da disponibilidade de nutrientes. Seu valor numa mesma amostra pode variar, entretanto, em função dos cuidados após a amostragem e das técnicas laboratoriais utilizadas. O presente trabalho objetivou avaliar o efeito do tipo de solvente, da relação solo/solvente, e da incubação de amostras úmidas, nos valores de pH de 49 solos catarinenses. Determinou-se o p H usando-se água (pH-H2O) ou solução de CaCl2 0,01 mol/L (pH-CaCl2 como solvente, nas relações solo/solvente de 1:1 e 1:2,5, nas amostras sem calcário, tanto nas que foram secas após a coleta (não incubadas) como naquelas incubadas úmidas durante 5 meses. O pH foi também determinado nas amostras da curva de neutralização da acidez de alguns solos, após a incubação, antes e depois da lavagem do excesso de sais das mesmas com água destilada. O uso de diferentes relações solo/solvente (1:1 e 1:2,5) não afetou os valores de pH em nenhum dos solventes usados. Houve uma alta associação positiva (r² = 0,96) entre os valores de pH determinados nos dois solventes, sendo que o pH-CaCl2 foi, em média, 0,6 unidades menor que o pH-H2O. A incubação das amostras úmidas diminuiu o pH de vários solos devido à acumulação de sais, e a diminuição foi maior no pH-H2O do que no pH-CaCl2. A percolação de água pelas amostras lavou o excesso de sais e corrigiu parcialmente o decréscimo causado pêlos sais no pH-H2O, porém teve pequeno efeito no pH-CaCl2. A recomendação de calcário para atingir valores de pH pré-estabelecidos foi superestimada quando as quantidades foram obtidas das curvas de pH-H2O das amostras não lixiviadas.

Soil pH is the most important parameter to evaluate nutrient availability in the soil. The pH value of a given sample, however, may vary according to the sample manipulation after sampling and to the laboratory analytical procedures. This experiment was carried out to determine the effect of the solvem type, of the soil/solvent ratio, and of the sample incubation on the pH values of 49 Brazilian soils. The soil pH was determined using water (pH-H2O) or calcium chloride (pH-CaCl2) as solvent, in two soil/solvent ratios (1:1 and 1:2.5). in all natural samples (without limestone), with and without wet incubation. The pH was also determinated in the samples of the neutralization curves of some soils, after incubation, before and after leaching out the excess of salts by rinsing the samples with destilled water. The soil/solvent ratio had no effect on soil pH, on both solvents. There was a good positive association (r² = 0.96) between pH values in both solvents, and lhe pH-CaCl2 was, on average, 0.6 units lower than pH-H2O. The incubation of the samples with moisture decreased soil pH due to salt accumulation, especially when determined using water as solvent. Rinsing lhe samples offset the effect caused by salts on pH-H2O but had a small effect on pH-CaCl2. The lime requirement of the soils was overestimated when obtained from the pH-H2O neutralization curves.

A formacao do arquiteto e a universidade

Analisa as relacoes entre a formacao do arquiteto e a universidade sob o ponto de vista do ensino de arquitetura. O artigo argumenta em favor da insercao desse ensino no contexto universitario (disciplinas universitarias afins). A escola, ou Faculdade de Arquitetura e Urbanismo da Universidade de Brasilia (FAU/UnB) e o principal objeto de analise. O artigo aponta, como um serio obstaculo ao intercambio academico, a forma como o ensino de projeto e ministrado. A analise compara duas concepcoes existentes sobre esse ensino, uma denominada disciplinar outra universitaria. O metodo de ensino de projeto correspondente a disciplinar e denominado de programa-projeto ou analise-sintese, e o segundo, de projeto conceitual. Para o primeiro, a universidade e um ambiente neutro; para o segundo, uma necessidade. O artigo argumenta em favor da insercao da arquitetura na universidade. Dois aspectos interdependentes sao enfatizados: a formacao intelectual e investigativa (pesquisa) dos estudantes.