Toxicological evaluation of lactose and chitosan delivered by inhalation

These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione ( GSSG), myeloperoxidase ( MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 +/- 2.27 versus 15.10 +/- 7.27 ( P = 0.011) for MPO and 0.89 +/- 0.68 versus 2.02 +/- 0.22 ( P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

The impact of the Brazilian family health on selected primary care sensitive conditions: A systematic review

Background Brazil has the largest public health-system in the world, with 120 million people covered by its free primary care services. The Family Health Strategy (FHS) is the main primary care model, but there is no consensus on its impact on health outcomes. We systematically reviewed published evidence regarding the impact of the Brazilian FHS on selective primary care sensitive conditions (PCSC). Methods We searched Medline, Web of Science and Lilacs in May 2016 using key words in Portuguese and English, without language restriction. We included studies if intervention was the FHS; comparison was either different levels of FHS coverage or other primary health care service models; outcomes were the selected PCSC; and results were adjusted for relevant sanitary and socioeconomic variables, including the national conditional cash transfer program (Bolsa Familia). Due to differences in methods and outcomes reported, pooling of results was not possible. Results Of 1831 records found, 31 met our inclusion criteria. Of these, 25 were ecological studies. Twenty-one employed longitudinal quasi-experimental methods, 27 compared different levels the FHS coverage, whilst four compared the FHS versus other models of primary care. Fourteen studies found an association between higher FHS coverage and lower post-neonatal and child mortality. When the effect of Bolsa Familia was accounted for, the effect of the FHS on child mortality was greater. In 13 studies about hospitalizations due to PCSC, no clear pattern of association was found. In four studies, there was no effect on child and elderly vaccination or low-birth weight. No included studies addressed breast-feeding, dengue, HIV/AIDS and other neglected infectious diseases. Conclusions Among these ecological studies with limited quality evidence, increasing coverage by the FHS was consistently associated with improvements in child mortality. Scarce evidence on other health outcomes, hospitalization and synergies with cash transfer was found

Reprodução na juventude: perfis sociodemográficos, comportamentais e reprodutivos na PNDS 2006

OBJETIVO: Analizar características sociodemográficas y de conductas sexual y reproductiva de mujeres jóvenes. MÉTODOS: Estudio poblacional transversal con representatividad nacional sobre el comportamiento sexual, anticonceptivo y reproductivo de 2.991 mujeres de 15 a 20 años en la Investigación Nacional de Demografía y Salud del Niño y de la Mujer (PNDS) 2006. Las jóvenes se clasificaron en tres grupos: iniciaron la vida sexual y se embarazaron antes de los 20 años (grupo A); iniciaron la vida sexual y no se embarazaron antes de los 20 (grupo B) y no iniciaron la vida sexual (grupo C). Mujeres de hasta 25 años se consideraron para el estudio de las tasas de embarazo y de sus consecuencias en la vida. Los análisis estadísticos consideraron los pesos y la planificación del muestreo complejo. La asociación entre dos variables categóricas fue evaluada por la prueba Chi-cuadrado. Para las conductuales, se utilizó el modelo linear global. RESULTADOS: Mujeres del grupo A eran principalmente negras, más pobres y con menor escolaridad. Tuvieron la primera relación sexual más precozmente, comportamiento anticonceptivo más desprotegido y menor conocimiento de la fisiología de la reproducción con relación al grupo B; las jóvenes del grupo C se caracterizaron por frecuentar más la escuela, y la preservación de la virginidad para el matrimonio fue relatada por 1/3 del grupo. En las mujeres con hasta 25 años, el embarazo antes de los 20 fue percibido con más consecuencias positivas que negativas en la vida amorosa, conyugal, social y autoestima. CONCLUSIONES: Hay asociación significativa entre embarazo antes de los 20 años con mayor pobreza y menor escolaridad. En ausencia de mejores condiciones de vida y de oportunidades, el embarazo, aunque no sea previsto, se establece como "proyecto de vida" en comparación con su inexistencia.OBJECTIVE: Analyze the sociodemographic characteristics and the sexual and reproductive behavior of young women. METHODS: A cross-sectional nationally representative study was performed about sexual, contraceptive and reproductive behavior with 2,991 women age 15 to 20 years in the National Survey on Demography and Health of Women and Children, 2006. The women were classified into three groups: sexual initiation and pregnancy before the age of 20 (group A); sexual initiation but no pregnancy before the age of 20 (group B) and no sexual initiation (group C). Women until age 25 years were included in the study about reasons for becoming pregnant and the implications for their lives. Statistical analysis considered survey weights and the complex sample design. The association between two categorical variables was assessed by chi-square test. The behavior variables were assessed using a global linear model. RESULTS: Women in group A were mainly black, poorer and with lower education level. These women had an early sexual initiation, less safe contraceptive behavior and less knowledge of reproduction physiology in comparison with group B; young women in group C were characterized by greater attendance at school and 1/3 of this group claimed to maintain their virginity until marriage. For women up to the age of 25, pregnancy before 20 years was perceived as having more positive than negative impacts upon their love life, spousal relationships, social lives and self-esteem. CONCLUSIONS: There is a significant association between pregnancy before the age of 20 and higher poverty and lower educational level. In the absence of better living conditions and opportunities, pregnancy, although unplanned, becomes "a plan for life", and is not seen as a lack of life planning.OBJETIVO: Analisar características sociodemográficas e do comportamento sexual e reprodutivo de mulheres jovens. MÉTODOS: Estudo populacional transversal com representatividade nacional sobre o comportamento sexual, contraceptivo e reprodutivo de 2.991 mulheres de 15 a 20 anos na Pesquisa Nacional de Demografia e Saúde da Criança e da Mulher 2006. As jovens foram classificadas em três grupos: iniciaram a vida sexual e engravidaram antes dos 20 anos (grupo A); iniciaram a vida sexual e não engravidaram antes dos 20 (grupo B) e não iniciaram a vida sexual (grupo C). Mulheres de até 25 anos foram consideradas para o estudo das razões da gravidez e de suas implicações na vida. As análises estatísticas consideraram os pesos e o planejamento amostral complexo. A associação entre duas variáveis categóricas foi avaliada pelo teste tipo qui-quadrado. Quanto às comportamentais, utilizou-se modelo linear global. RESULTADOS: Mulheres do grupo A eram principalmente negras, mais pobres e com menor escolaridade. Tiveram a primeira relação sexual mais precocemente, comportamento contraceptivo mais desprotegido e menor conhecimento da fisiologia da reprodução em relação ao grupo B; as jovens do grupo C caracterizaram-se por maior frequência à escola e a preservação da virgindade para o casamento foi alegada por um 1/3 desse grupo. Para as mulheres com até 25 anos, a gravidez antes dos 20 foi percebida como tendo implicações mais positivas que negativas na vida amorosa, conjugal, social e autoestima. CONCLUSÕES: Há associação significativa entre gravidez antes dos 20 anos com maior pobreza e menor escolaridade. Na ausência de melhores condições de vida e de oportunidades, a gravidez, embora não prevista, configura-se como "projeto de vida" e não sua mera ausência

Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences

Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online ‘TB-Profiler’ tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing

Typologies of post-divorce coparenting and parental well-being, parenting quality and children’s psychological adjustment

First published online: 30 October 2015The aim of this study was to identify post-divorce coparenting profiles and examine whether these profiles differentiate between levels of parents’ well-being, parenting practices, and children’s psychological problems. Cluster analysis was conducted with Portuguese heterosexual divorced parents (N = 314) to yield distinct postdivorce coparenting patterns. Clusters were based on parents’ self-reported coparenting relationship assessed along four dimensions: agreement, exposure to conflict, undermining/support, and division of labor. A three cluster solution was found and replicated. Parents in the highconflict coparenting group exhibited significantly lower life satisfaction, as well as significantly higher divorce-related negative affect and inconsistent parenting than parents in undermining and cooperative coparenting clusters. The cooperative coparenting group reported higher levels of positive family functioning and lower externalizing and internalizing problems in their children. These results suggested that a positive coparenting alliance may be a protective factor for individual and family outcomes after parental divorce

Coupling changes in cell shape to chromosome segregation

Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts