Failure of programmed cell death and differentiation as causes of tumors: some simple mathematical models.

Most models of tumorigenesis assume that the tumor grows by increased cell division. In these models, it is generally supposed that daughter cells behave as do their parents, and cell numbers have clear potential for exponential growth. We have constructed simple mathematical models of tumorigenesis through failure of programmed cell death (PCD) or differentiation. These models do not assume that descendant cells behave as their parents do. The models predict that exponential growth in cell numbers does sometimes occur, usually when stem cells fail to die or differentiate. At other times, exponential growth does not occur: instead, the number of cells in the population reaches a new, higher equilibrium. This behavior is predicted when fully differentiated cells fail to undergo PCD. When cells of intermediate differentiation fail to die or to differentiate further, the values of growth parameters determine whether growth is exponential or leads to a new equilibrium. The predictions of the model are sensitive to small differences in growth parameters. Failure of PCD and differentiation, leading to a new equilibrium number of cells, may explain many aspects of tumor behavior--for example, early premalignant lesions such as cervical intraepithelial neoplasia, the fact that some tumors very rarely become malignant, the observation of plateaux in the growth of some solid tumors, and, finally, long lag phases of growth until mutations arise that eventually result in exponential growth.

Trends in diabetes incidence from 1992 to 2015 and projections for 2024: A Portuguese General Practitioner’s Network study

Background: Diabetes is known as a major cause of morbidity and mortality worldwide. Portugal is known as the European country with the highest prevalence of this disease. While diabetes prevalence data is updated annually in Portugal, the General Practitioner’s (GP) Sentinel Network represents the only data source on diabetes incidence. This study describes the trends in Diabetes incidence, between 1992 and 2015, and estimate projections for the future incidence rates in Portugal until 2024. Methods: An ecological time-series study was conducted using data from GP Sentinel Network between 1992 and 2015. Family doctors reported all new cases of Diabetes in their patients’ lists. Annual trends were estimated through Poisson regression models as well as the future incidence rates (until 2024), sex and age group stratified. Incidence rate projections were adjusted to the distribution of the resident Portuguese population given Statistics Portugal projections. Results: The average increase in Diabetes incidence rate was in total 4.29% (CI95% 3.80–4.80) per year under study. Until 1998–2000, the annual incidence rate was higher in women, and from 1998–2000 to 2013–2015 turn out to be higher in men. The incidence rate projected for 2022–2024 was 972.77/105 inhabitants in total, and 846.74/105 and 1114.42/105, respectively, in women and men. Conclusions: This is the first study in Portugal to estimate diabetes incidence rate projections. The disturbing reported projections seem realistic if things continue as in the past. Actually, effective public health policies will need to be undertaken to minimize this alarming future scenario.

Tri-level study: modification. Task 5: an examination of driver characteristics and collision producing errors of accident and traffic violation repeaters. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Identification of specific problems and countermeasures targets for reducing alcohol related casualties. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Neuromuscular synapses mediate motor axon branching and motoneuron survival during the embryonic period of programmed cell death

The embryonic period of motoneuron programmed cell death (PCD) is marked by transient motor axon branching, but the role of neuromuscular synapses in regulating motoneuron number and axonal branching is not known. Here, we test whether neuromuscular synapses are required for the quantitative association between reduced skeletal muscle contraction, increased motor neurite branching, and increased motoneuron survival. We achieved this by comparing agrin and rapsyn mutant mice that lack acetylcholine receptor (AChR) clusters. There were significant reductions in nerve-evoked skeletal muscle contraction, increases in intramuscular axonal branching, and increases in spinal motoneuron survival in agrin and rapsyn mutant mice compared with their wild-type littermates at embryonic day 18.5 (E18.5). The maximum nerve-evoked skeletal muscle contraction was reduced a further 17% in agrin mutants than in rapsyn mutants. This correlated to an increase in motor axon branch extension and number that was 38% more in agrin mutants than in rapsyn mutants. This suggests that specializations of the neuromuscular synapse that ensure efficient synaptic transmission and muscle contraction are also vital mediators of motor axon branching. However, these increases in motor axon branching did not correlate with increases in motoneuron survival when comparing agrin and rapsyn mutants. Thus, agrin-induced synaptic specializations are required for skeletal muscle to effectively control motoneuron numbers during embryonic development. (C) 2003 Elsevier Science (USA). All rights reserved.

Nanotossicologia dei quantum dot di CdS in linee cellulari umane

Le nanotecnologie sono un settore emergente in rapida crescita, come dimostra l'esplosione del mercato dei prodotti ad esso collegati. I quantum dot di cadmio solfuro (CdS QD) sono ampiamente utilizzati per la produzione di materiali semiconduttori e dispositivi optoelettronici; tuttavia, non sono ancora completamente chiari gli effetti di questi nanomateriali sulla salute umana. Questo lavoro di dottorato si pone l'obbiettivo di definire il potenziale citotossico e genotossico dei CdS QD in linee cellulari umane e definirne il meccanismo implicato. A questo scopo, essendo il fegato uno dei principali organi di accumulo del cadmio e dei nanomateriali a base di cadmio, è stata utilizzata la linea cellulare HepG2 derivante da un epatocarcinoma umano. È stato evidenziato, in seguito all'assorbimento, da parte delle cellule, dei CdS QD, un effetto citotossico, con conseguente modulazione dell'espressione genica di una serie di geni coinvolti sia nei processi di rescue (autofagia, risposta allo stress) sia in quelli di morte cellulare programmata. È stato, inoltre, dimostrata l'assenza di un rilevante effetto genotossico dipendente da questi nanomateriali. Infine, è stato osservato che cellule esposte ai CdS QD presentano mitocondri con un potenziale di membrana alterato, con conseguente alterazione della funzionalità di tale organello, pur conservando l'integrità del DNA mitocondriale.

RELAÇÕES DE SUPORTE E BEM-ESTAR NO TRABALHO EM PESSOAS COM DEFICIÊNCIA

Desde tempos remotos é notória a busca da humanidade para entender e conquistar a felicidade, qualidade de vida, bem-estar e saúde na sua plenitude bio-psico-social. Assim, o objetivo geral deste estudo foi analisar as relações entre percepções de suporte (social, social no trabalho e organizacional) e bem-estar no trabalho (satisfação no trabalho, envolvimento com o trabalho e comprometimento organizacional afetivo) em trabalhadores com deficiência, pois são poucas as pesquisas sobre pessoas com deficiência (PCD). O propósito em abordar o trabalho é por ser um importante elemento de integração social e por constituir um símbolo de reconhecimento social, valorizando a capacidade de estreitar contatos e de estabelecer relações sociais. Deste estudo, participaram 44 trabalhadores com algum tipo de deficiência que atuam em cargos operacionais, técnicos e administrativos. Todos foram escolhidos por conveniência, sendo 24 (54,5%) do sexo masculino e 20 (45,5%) do sexo feminino, com idade entre 18 e 65 anos. Foi possível classificar as deficiências dos participantes em quatro categorias: deficiência nos membros superiores: 9 (20,5%) trabalhadores; deficiência nos membros inferiores: 11 (25%) trabalhadores; deficiência auditiva: 21 (47,7%) trabalhadores; deficiência visual: 3 (6,8%) trabalhadores. Para a coleta de dados foi utilizado questionário de auto-preenchimento, composto de seis escalas que avaliam satisfação no trabalho, envolvimento com o trabalho e comprometimento organizacional, além de suporte social, suportes social no trabalho e organizacional. Foram realizadas análises estatísticas descritivas, testadas diferenças entre médias, bem como calculados coeficientes de correlação entre variáveis. Os resultados apontam que em termos de satisfação no trabalho, não revelam discrepâncias entre estudos realizados com trabalhadores sem deficiências (considerados normais ). Também foi possível observar que as PCD declaram ter orgulho da empresa em que trabalham, além de estarem contentes, entusiasmadas, interessadas e animadas com a organização empregadora. O estudo revelou que as PCD obtêm de sua rede social, ajuda emocional que lhes proporciona sentimento de apoio frente às dificuldades ou carências afetivas, pois provavelmente entendam que podem contar com essa rede para comemorar realizações e sucessos, da mesma forma que receber carinho e consolo quando se frustram ou passam por algum momento triste. É possível afirmar que as PCD percebem que essa mesma rede seria capaz de lhes prover algum apoio prático, como receber informações acerca de sua saúde, talvez reabilitação, também informações para atualização profissional ou até acompanhamento do seu desenvolvimento, inclusive busca de novas oportunidades e desafios para crescimento pessoal e profissional. Os resultados desta pesquisa indicam que as PCD tendem a manter uma forte convicção de que a empresa em que trabalham preocupa-se com seu bem-estar e está disposta a oferecer ajuda diante uma necessidade. Demais resultados sinalizam que as PCD tendem a aumentar o seu vínculo com o trabalho vivenciando mais satisfação na medida em que também aumentam os suportes ofertados pela organização, pela rede social no contexto do trabalho e fora dele. A análise de todo o conteúdo confeccionado é a grande contribuição deste estudo, por ser considerado pioneiro nesta discussão, mas futuros estudos podem vir a confirmar tais resultados e corroborar com mais informações.(AU)

Effect of methane concentration in hydrogen plasma on hydrogen impurity incorporation in thick large-grained polycrystalline diamond films

We investigate the impact of methane concentration in hydrogen plasma on the growth of large-grained polycrystalline diamond (PCD) films and its hydrogen impurity incorporation. The diamond samples were produced using high CH4 concentration in H2 plasma and high power up to 4350 W and high pressure (either 105 or 110 Torr) in a microwave plasma chemical vapor deposition (MPCVD) system. The thickness of the free-standing diamond films varies from 165 µm to 430 µm. Scanning electron microscopy (SEM), micro-Raman spectroscopy and Fourier-transform infrared (FTIR) spectroscopy were used to characterize the morphology, crystalline and optical quality of the diamond samples, and bonded hydrogen impurity in the diamond films, respectively. Under the conditions employed here, when methane concentration in the gas phase increases from 3.75% to 7.5%, the growth rate of the PCD films rises from around 3.0 µm/h up to 8.5 µm/h, and the optical active bonded hydrogen impurity content also increases more than one times, especially the two CVD diamond specific H related infrared absorption peaks at 2818 and 2828 cm−1 rise strongly; while the crystalline and optical quality of the MCD films decreases significantly, namely structural defects and non-diamond carbon phase content also increases a lot with increasing of methane concentration. Based on the results, the relationship between methane concentration and diamond growth rate and hydrogen impurity incorporation including the form of bonded infrared active hydrogen impurity in CVD diamonds was analyzed and discussed. The effect of substrate temperature on diamond growth was also briefly discussed. The experimental findings indicate that bonded hydrogen impurity in CVD diamond films mainly comes from methane rather than hydrogen in the gas source, and thus can provide experimental evidence for the theoretical study of the standard methyl species dominated growth mechanism of CVD diamonds grown with methane/hydrogen mixtures.

Indicador de vulnerabilidade agropecuária a extremos climáticos para o nordeste do Brasil

The effects of climate change on human societies have become the focus of many researchers for their research. Understanding weather patterns (circulation of the atmosphere, precipitation, temperature) is essences for predicting extreme weather, but analyze how these extreme events act in our society and look for ways to reduce the impact caused by these events is the great challenge. Using a concept very in the humanities and social sciences to understand these impacts and the adaptation of the society's vulnerability. The objective of this work is to develop and apply a methodology for evaluating fining scale and quantify the vulnerability of the Brazilian Northeast to climatic extremes, developing a methodology that combines aspects of vulnerability to drought, as well as socioeconomic and climatic indicators used to assess exposure, ability to adaptation and the sensitivity of geographical microregions of the region. The assessment of the susceptibility or degree of exposure to risk is the regional using the SPI (Standardized Precipitation Index) by the degree of magnitude dried (MD), the rate of precipitation such as PCD (Precipitation Concentration Degree) and PCP (Precipitation Period Concentration) helped characterize and regional climatology, these indices showed satisfactory results in the pilot study of Rio Grande do Norte to assess the degree of exposure to drought. Regarding sensitivity agricultural / livestock multivariate statistical technique to factor analysis showed acceptable results for the proposed model using data for the period 1990-1999 (P1). The application of the analysis of vulnerability considering the adaptive capacity, as the adaptive disability have almost similar results with much of the region's vulnerability to extreme south of Bahia state as a part of the semiarid region has a degree of vulnerability among moderate and mean

Legonaridin, a new member of linaridin RiPP from a Ghanaian Streptomyces Isolate

Acknowledgements KK, MJ, RE and HD are grateful for financial support through the Leverhulme Trust-Royal Society Africa award (AA090088). MJ, RE, HD, JT and KH thank EU FP7 for financial support (contract no. 312184). HD thanks the School of Natural and Computing Sciences, University of Aberdeen, for a PhD scholarship to XLW. PCD gratefully acknowledges grants from the National Institute of Health (GM097509 and GMS10RR029121). We thank the Bruker Therapeutic Discovery Mass Spectrometry Center for recording the MSn spectra.

Diagnosing primary ciliary dyskinesia: an international patient perspective

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by progressive sinopulmonary disease, with symptoms starting soon after birth. A European Respiratory Society (ERS) Task Force aims to address disparities in diagnostics across Europe by providing evidence-based clinical practice guidelines. We aimed to identify challenges faced by patients when referred for PCD diagnostic testing. A patient survey was developed by patient representatives and healthcare specialists to capture experience. Online versions of the survey were translated into nine languages and completed in 25 countries. Of the respondents (n=365), 74% were PCD-positive, 5% PCD-negative and 21% PCD-uncertain/inconclusive. We then interviewed 20 parents/patients. Transcripts were analysed thematically. 35% of respondents visited their doctor more than 40 times with PCD-related symptoms prior to diagnostic referral. Furthermore, the most prominent theme among interviewees was a lack of PCD awareness among medical practitioners and failure to take past history into account, leading to delayed diagnosis. Patients also highlighted the need for improved reporting of results and a solution to the “inconclusive” diagnostic status. These findings will be used to advise the ERS Task Force guidelines for diagnosing PCD, and should help stakeholders responsible for improving existing services and expanding provision for diagnosis of this rare disease.

Effect of implementation of a preconception counselling resource for women with diabetes: A population based study

Aim To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. Methods A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n = 135), including a viewed-DVD subgroup (n = 58), were compared with an historical cohort (pre-DVD, n = 114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. Results Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8 mmol/mol]; p = 0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8 mmol/mol], P < 0.001; planned pregnancy (88% vs. 59%, P < 0.001); taken folic acid preconception (81% vs. 43%, P = 0.001); and had HbA1c recorded preconception (88% vs. 53%, P < 0.001) than the pre-DVD cohort. Conclusions Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

Conocimientos, actitudes y prácticas de cuidadores de personas con discapacidad, en procesos de inclusión social en el municipio Madrid, Cundinamarca

La inclusión social de personas con discapacidad (PcD) depende de múltiples factores económicos, sociales, políticos y culturales, que afectan su desarrollo social. Uno de los factores que genera mayor exclusión social, corresponde a las barreras actitudinales que se identifican en el entorno cercano. El objetivo de este artículo es identificar conocimientos, actitudes y prácticas de cuidadores primarios, acerca de la discapacidad y el cuidado que ofrecen a las PcD vinculadas a los servicios del Centro Ambulatorio Gustavo Escallón Cayzedo de la Fundación Santa Fe de Bogotá (CAGEC), en el municipio de Madrid, Cundinamarca.

Enhancing bioactive fatty acids of the meat from lambs reared in intensive systems through nutritional modulation

Tese de Doutoramento em Ciências Veterinárias, especialidade de Produção Animal

A política de inclusão e o percurso de formação profissional do estudante com deficiência no Instituto Federal de Educação : um estudo de caso do Campus Planaltina

Dissertação apresentada para obtenção do grau de mestre no âmbito do Mestrado em Educação Social e Intervenção Comunitária da Escola Superior de Educação do Instituto Politécnico de Santarém.