Generating properly differentiated embryonic structures in vitro from pluripotent stem cells remains a challenge. Here we show that instruction of aggregates of mouse embryonic stem cells with an ...experimentally engineered morphogen signalling centre, that functions as an organizer, results in the development of embryo-like entities (embryoids). In situ hybridization, immunolabelling, cell tracking and transcriptomic analyses show that these embryoids form the three germ layers through a gastrulation process and that they exhibit a wide range of developmental structures, highly similar to neurula-stage mouse embryos. Embryoids are organized around an axial chordamesoderm, with a dorsal neural plate that displays histological properties similar to the murine embryo neuroepithelium and that folds into a neural tube patterned antero-posteriorly from the posterior midbrain to the tip of the tail. Lateral to the chordamesoderm, embryoids display somitic and intermediate mesoderm, with beating cardiac tissue anteriorly and formation of a vasculature network. Ventrally, embryoids differentiate a primitive gut tube, which is patterned both antero-posteriorly and dorso-ventrally. Altogether, embryoids provide an in vitro model of mammalian embryo that displays extensive development of germ layer derivatives and that promises to be a powerful tool for in vitro studies and disease modelling.
OBJECTIVEDescribe consumption patterns for monetary and non-monetary acquisition of medicines according to age and income groups, highlighting pharmaceuticals associated with health programs with ...specific access guarantees.METHODSDescriptive observational study using microdata from the 2017-2018 Pesquisa de Orçamentos Familiares (Household Budget Survey, POF/IBGE). We initially reviewed programs/policies with specific guarantees of access to medicines in the SUS. Using the pharmaceutical product list of POF-4 (chart 29 of the questionnaire on individual expenditures), we selected the medicines related to these programs. We then described frequencies and percentages for not reporting medicine consumption and for reporting consumption (either through monetary or non-monetary acquisition) according to age and income groups. For medicines with distinctive access guarantees, we compared average monthly values of acquisitions and consumption patterns by age and income.RESULTS63% of those in the ≤ 2 minimum wage (MW) household income group did not report consuming medicines in the last month. Among those earning > 25 MW, 44.3% did not report consumption. Non-monetary acquisitions of medicines were mainly reported for the < 10 MW group and for the elderly and accounted for 20.5% of the total consumption of medicines (in value). For policies with specific access guarantees, non-monetary acquisitions reached 33.6% of total consumption. This percentage varied for the various selected medicines: vaccines, 83.3%; cancer drugs, 70.3%; diabetes, 47.9%; hypertension, 35.9%; asthma and bronchitis, 29.2%; eye problems, 14%; prostate and urinary tract, 10.7%; gynecological, 11.6%; and contraceptives, 9.7%.CONCLUSIONShares for non-monetary acquisitions of medicines are still low but benefit mainly lower-income and older age groups. Policies and programs with specific access guarantees to medicines have increased access. Results suggest the need to strengthen and expand pharmaceutical care policies.
Estudos com edições anteriores da Pesquisa de Orçamentos Familiares (POF) indicam que, no Brasil, pagar um plano de saúde aumenta o percentual da renda gasto com saúde e não reduz a probabilidade de ...ter gastos excessivos com saúde. Descrevem-se relações entre gastos com planos de saúde, renda e faixas etárias, destacando o efeito de ter plano sobre a probabilidade de comprometer mais de 40% da renda com despesas relacionadas à saúde. Análise de microdados da POF 2017/2018 para determinar o comprometimento da renda domiciliar per capita dos pagantes de planos por faixa etária e por tipo de plano, e regressão logística para fatores associados a comprometer mais de 40% da renda com despesas de saúde. Em 12 meses, R$ 78,1 bilhões foram gastos com planos médicos por 22,1 milhões de pessoas. O comprometimento da renda com planos individuais aumenta consistentemente com a idade, passando de 4,5% da renda domiciliar per capita (< 19 anos) para 10,6% dessa renda (79 anos ou mais). A probabilidade de comprometer mais de 40% da renda com despesas de saúde diminui com a renda, cresce com a idade e é maior para quem paga plano de saúde. A despesa apenas com os planos supera 40% da renda domiciliar per capita para 5,6% das pessoas com 60 anos ou mais que pagam planos individuais e para 4% das que pagam planos empresariais. As pessoas nas faixas de idade mais altas e faixas de renda mais baixas são as com maior probabilidade de comprometer mais de 40% da renda com despesas de saúde. Rever as regras de reajuste por idade dos planos é uma alternativa para tentar mitigar esse problema.
According to studies using previous editions of the Household Budgets Survey (POF) in Brazil, paying for a healthcare plan increases the percentage of income spent on health and fails to reduce the probability of incurring excessive health expenditures. The study’s objective was to describe relations between expenditures on healthcare plans, income, and age groups, highlighting the effect of having a plan on the probability of committing more than 40% of income on health-related expenditures. An analysis of the POF 2017/2018 determined the commitment of per capita household income for payers of plans by age group and type of plan and logistic regression for factors associated with committing more than 40% of income to health-related expenditures. In 12 months, 22.1 million Brazilians spent BRL 78.1 billion on private medical insurance. The share of income spent on individual plans increases consistently with age, from 4.5% of per capita household income (at < 19 years) to 10.6% of this income (at 79 years or older). The probability of committing more than 40% of income to health expenditures decreases with income, increases with age, and is higher for those paying for health plans. Spending on healthcare plans alone exceeds 40% of per capita household income for 5.6% of Brazilians 60 years or older who pay for individual plans and for 4% of those who pay for company plans. Persons in the oldest age groups and in the lowest income brackets show the highest likelihood of spending more than 40% of their income on healthcare. A revision of the plans’ adjustment by age is an alternative for attempting to mitigate this problem.
Estudios con ediciones anteriores de la Encuesta de Presupuestos Familiares (POF) indican que, en Brasil, pagar un plan de salud aumenta el porcentaje de la renta gastado con salud y no reduce la probabilidad de tener gastos excesivos con la salud. El objetivo fue describir las relaciones entre gastos con planes de salud, renta y franjas de edad, destacando el efecto de tener un plan sobre la probabilidad de comprometer más de un 40% de la renta con gastos relacionados con la salud. Se realizó un análisis de microdatos de la POF 2017/2018 para determinar el comprometimiento de la renta domiciliaria per cápita de los pagadores de planes por franja etaria y por tipo de plan, así como una regresión logística para factores asociados con comprometer más de un 40% de la renta con gastos de salud. En 12 meses, BRL 78,1 mil millones se gastaron con planes médicos por 22,1 millones de personas. El comprometimiento de la renta con planes individuales aumenta consistentemente con la edad, pasando de 4,5% de la renta domiciliaria per cápita (< 19 años) al 10,6% de esa renta (79 años o más). La probabilidad de comprometer más de un 40% de la renta con gastos de salud disminuye con la renta, crece con la edad y es mayor para quien paga un plan de salud. El gasto solo con los planes supera un 40% de la renta domiciliaria per cápita para un 5,6% de las personas con 60 años o más que pagan planes individuales y para un 4% de los que pagan planes empresariales. Las personas en las franjas de edad más altas y franjas de renta más bajas son las que tienen mayor probabilidad de comprometer más de un 40% de la renta con gastos de salud. Revisar las reglas de reajuste por edad de los planes es una alternativa para intentar mitigar ese problema.
According to studies using previous editions of the Household Budgets Survey (POF) in Brazil, paying for a healthcare plan increases the percentage of income spent on health and fails to reduce the ...probability of incurring excessive health expenditures. The study's objective was to describe relations between expenditures on healthcare plans, income, and age groups, highlighting the effect of having a plan on the probability of committing more than 40% of income on health-related expenditures. An analysis of the POF 2017/2018 determined the commitment of per capita household income for payers of plans by age group and type of plan and logistic regression for factors associated with committing more than 40% of income to health-related expenditures. In 12 months, 22.1 million Brazilians spent BRL 78.1 billion on private medical insurance. The share of income spent on individual plans increases consistently with age, from 4.5% of per capita household income (at < 19 years) to 10.6% of this income (at 79 years or older). The probability of committing more than 40% of income to health expenditures decreases with income, increases with age, and is higher for those paying for health plans. Spending on healthcare plans alone exceeds 40% of per capita household income for 5.6% of Brazilians 60 years or older who pay for individual plans and for 4% of those who pay for company plans. Persons in the oldest age groups and in the lowest income brackets show the highest likelihood of spending more than 40% of their income on healthcare. A revision of the plans' adjustment by age is an alternative for attempting to mitigate this problem.
Par3 in chick lens placode development Melo, Maraysa de Oliveira; Moraes Borges, Ricardo; Yan, Chao Yun Irene
Genesis (New York, N.Y. : 2000),
June 2017, 2017-06-00, 20170601, Letnik:
55, Številka:
6
Journal Article
Recenzirano
The lens originates from a simple cuboidal epithelium, which, on its basal side, contacts the optic vesicle, whilst facing the extraembryonic environment on its apical side. As this epithelium ...changes into the pseudostratified lens placode, its cells elongate and become narrower at their apical ends. This is due to the formation of an apical actin network, whose appearance is restricted to cells of the placodal region, as a result of region‐specific signaling mechanisms that remain largely unknown. Here, we investigated the role of the polarity protein PAR3 and the phosphorylation state of its Threonine 833 (T833) aPKC‐binding site in the recruitment of aPKC and in the establishment of actin network in the chick lens placode. Overexpression of wild type PAR3 recruited aPKC and punctate actin clusters to the basolateral membranes of the placodal cells. Recruitment of aPKC depended on the charge of the residue that replaced the T833 residue. In contrast, induction of the ectopic actin spots was independent on the charge of this residue.
Intestinal villi of
Caiman yacare
form longitudinal folds instead of the finger-like projections of most birds and mammals. Moreover, they lack Crypts of Lieberkühn and the lamina epithelialis ...organization is dynamic, changing from pseudostratified to simple columnar epithelium after feeding. Because of these differences, we sought to verify whether intestinal villi of the crocodilian
Caiman yacare
are functionally compartmentalized along their length similarly to the finger-like villi that harbors Crypt of Lieberkühn. For this,
Caiman yacare
were force-fed soybean oil, the intestinal mucosa was harvested and analyzed under light microscopy after lipid staining or immunohistochemistry for the proliferative marker PCNA. Functional compartmentalization was assessed by evaluating differences in lipid absorption along intestinal villi base-to-tip axis, by localizing the proliferative enterocytes and by verifying whether such cells were capable of absorbing lipids. Histological morphometric analyses of the extent of enterocyte hypertrophy caused by lipid inclusions and the contribution of such inclusions to histological remodeling from pseudostratified to simple columnar epithelium were also evaluated. Although lacking Crypts of Lieberkühn, enterocytes present at villi base were PCNA positive and devoid of the great amount of lipid inclusions observed in the other intestinal villi domains, in a similar pattern to finger-like villi. Enterocytes doubled their volume because of lipid inclusions, and in spite of such enterocyte hypertrophy, lamina epithelialis continued to be pseudostratified within lateral sides, whereas villi tip were organized in a simple columnar epithelium.
Although it is stated that dietary lipids are absorbed proximally in the small intestine of vertebrates, there are variations of the primary site for lipid absorption even when closely related ...species are considered. Moreover, there are evidences suggesting that the small intestine distal segments are equally capable of absorbing lipids, although it is not known whether it is the case for crocodilians. The lipoprotein assembling process and secretion routes are also largely unknown for crocodilians and therefore, assumed to be similar to mammals. The aims of this study were to identify the crocodilian
Caiman yacare
intestinal segments where lipid absorption occurs, to characterize the intestinal lipoproteins secreted by enterocytes and to evaluate lymphatic system contribution to exportation of lipoproteins from the intestine. For this, soybean oil was injected into
C. yacare
stomach and intestinal lipid absorption process was characterized by light and electron microscopy 24, 48 and 72 h after oil injection. The same amount of lipid inclusions was present in the duodenum, in the proximal jejunum and in the distal jejunum. The colon also showed a few lipid inclusions. The bulk of lipoproteins secreted by the enterocytes was <200 nm in diameter and was observed inside the lymphatic central lacteals. Lipid inclusions were absent from the intestinal mucosa and from the lacteals of the control animals. Finally, the high amount of lipids ingested did not recruit innate immune cells to the mucosa in any intestinal segment, suggesting that soybean oil is not pro-inflammatory for intestinal mucosa of
C. yacare
in the short time analyzed.
Spider venoms, despite their toxicity, represent rich sources of pharmacologically active compounds with biotechnological potential. However, in view of the large diversity of the spider species, the ...full potential of their venom molecules is still far from being known. In this work, we report the purification and structural and functional characterization of GiTx1 (β/κ-TRTX-Gi1a), the first toxin purified from the venom of the Brazilian tarantula spider Grammostola iheringi. GiTx1 was purified by chromatography, completely sequenced through automated Edman degradation and tandem mass spectrometry and its structure was predicted by molecular modeling. GiTx1 has a MW of 3.585 Da, with the following amino acid sequence: SCQKWMWTCDQKRPCCEDMVCKLWCKIIK. Pharmacological activity of GiTx1 was characterized by electrophysiology using whole-cell patch clamp on dorsal root ganglia neurons (DRG) and two-electrode voltage-clamp on voltage-gated sodium and potassium channels subtypes expressed in Xenopus laevis oocytes. GiTx1, at 2 μM, caused a partial block of inward (∼40%) and outward (∼20%) currents in DRG cells, blocked rNav1.2, rNav1.4 and mNav1.6 and had a significant effect on VdNav, an arachnid sodium channel isoform. IC50 values of 156.39 ± 14.90 nM for Nav1.6 and 124.05 ± 12.99 nM for VdNav, were obtained. In addition, this toxin was active on rKv4.3 and hERG potassium channels, but not Shaker IR or rKv2.1 potassium channels. In summary, GiTx1 is a promiscuous toxin with multiple effects on different types of ion channels.
Display omitted
•GiTx1(β/κ-theraphotoxin-Gi1a) is a toxin from the venom of the spider G.iheringi.•Structural data suggest GiTx1 adopts the ICK (Inhibitory Cystine Knot) conformation.•GiTx1 is toxic to mice and flies.•GiTx1 blocks total/partially Navs(1.2,1.3,1.4,1.5,1.6) and Navs from invertebrates.•GiTx1 inhibits some Kvs, as Kv4.3 and ERG.
The aim of this study was to evaluate the prebiotic effect of burdock (Arctium lappa) in commercial poultry. Four experiments were conducted to evaluate the performance parameters and the protection ...after challenge with Salmonella Enteritidis and Salmonella Kedougou, with and without Bifidobacterium probiotic. In two trials, the chickens were fed with flour burdock 1% during 42 days. In the other two, the chickens were fed with fructan extracted from burdock (inulin), by gavage, at a concentration of 100 mg/bird, during the first three days of life. The results showed that the broilers treated with burdock flour showed underperformed, with less weight gain from the second week, and the worst results in the fattening stage. The treated birds had diarrhea and impaired intestinal integrity. However, the groups treated with the flour had a lower rate of intestinal colonization by Salmonella Kedougou, after challenge. No statistically significant differences were detected in the performance parameters of broilers receiving the inulin, and the morphometric analysis showed no lesions in the intestinal villi. However, there was no protection in the challenge with Salmonella Enteritidis, regardless of association with probiotic. These results demonstrated that the manner of administration has influence on the prebiotic effect of burdock. The burdock flour was administered for 42 days, which may have influenced intestinal mucosal injury. Instead, the inulin was given only in the first three days, which may have been insufficient for protection against Salmonella. New experiments are needed to determine an able formulation for a protective effect, without negative impact on growth, weight gain and feed conversion of the supplemented animals.
RESUMO: Este projeto teve por objetivo avaliar o efeito prebiótico da bardana (Arctium lappa) em aves comerciais. Foram realizados quatro experimentos para avaliar os parâmetros zootécnicos e o grau de proteção após o desafio com Salmonella Kedougou e Salmonella Enteritidis, com e sem a adição de probióticos à base de Bifidobacterium. Em dois experimentos, as aves receberam a farinha de bardana 1% na ração, durante 42 dias. Nos outros dois, as aves receberam o frutano extraído da bardana (inulina), por gavagem, na concentração de 100 mg/ave, nos três primeiros dias de vida. Os resultados demonstraram que os frangos tratados com farinha de bardana apresentaram desempenho zootécnico inferior ao controle, com menor ganho de peso a partir da segunda semana e piores resultados na fase de engorda. As aves tratadas apresentaram diarreia e comprometimento da integridade intestinal. Em contrapartida, os grupos tratados com a farinha tiveram menor taxa de colonização intestinal por Salmonella Kedougou, após o desafio. Não foram detectadas diferenças estatisticamente significativas nos parâmetros zootécnicos dos frangos que receberam a inulina, e a análise morfométrica não evidenciou lesões nas vilosidades intestinais. No entanto, não houve proteção no desafio por Salmonella Enteritidis, independentemente da associação com probiótico. Esses resultados demonstraram que o modo de administração tem influência sobre o efeito prebiótico da bardana. A farinha de bardana foi administrada por 42 dias, o que pode ter causado a lesão da mucosa intestinal. Em contrapartida, a inulina foi administrada apenas nos primeiros três primeiros dias, o que pode ter sido insuficiente para proteção contra Salmonella. Novos experimentos são necessários para determinar uma formulação capaz de promover efeito protetor, sem impacto negativo no crescimento, ganho de peso e conversão alimentar dos animais suplementados.
PDF
