Hepatitis B Virus infection in HIV-positive population in Brazil: results of a survey in the state of Mato Grosso and a comparative analysis with other regions of Brazil

BACKGROUND: End-stage liver disease is currently a major concern among HIV-positive individuals due to co-infection with hepatotropic virus. Hepatitis C has been pointed out as a remarkable factor for that. More recently, hepatitis B virus (HBV) infection has also been found to play a role on liver disease in this population. HIV-HBV co-infection prevalence remains largely unknown in vast areas of Brazil. The objective of the present study was to estimate the prevalence of HBV and HDV infection in HIV-infected subjects living in the state of Mato Grosso, in the Central region of Brazil, and compare it to other Brazilian studies. We also assess epidemiologic data regarding risk factors and vaccinal status. METHODS: HIV-positive individuals followed at the Central Laboratory of the Department of Public Health of Mato Grosso in the city of Cuiabá composed the sample. Participants answered a specific questionnaire and had a blood sample taken and tested for serologic markers. RESULTS: A thousand individuals were interviewed and tested for HBsAg, anti-HBc, anti-HBs and anti-HDV if positive for HBsAg. Measurements of CD4 and viral load for HIV-1 were also performed. Overall prevalence of HBV exposure (anti-HBc +ve) was 40.0%, and 3.7% for HBsAg. This prevalence data was similar or slightly lower than for other Brazilian regions, which ranged from 40% and 3% to 71% and 24%, respectively. Testing for anti-HDV in the 37 HBsAg positive patients was positive in only one subject. Factors that showed independent association with HBV exposure, after adjustment, were: male gender, older age groups, tattooing, and reporting more than ten sexual partners throughout life (p < 0.01). Eighty-one (27.5%) out of 291 HBV-unexposed individuals who reported vaccination were anti-HBs positive. Anti-HBs prevalence was higher among those who had higher levels of CD4 by multivariate analysis. CONCLUSION: Our data showed HBV infection prevalence similar or slightly lower than that reported in other regions of Brazil. In addition, our data revealed a less important role for drug injection in the spread of HIV and HBV in Mato Grosso compared to other regions of the country. The high rate of non-vaccinated subjects among this HBV-unexposed, HIV-infected population is a matter of considerable health concern in this region. The relationship between CD4 levels and HBV vaccine response found in the present study reinforces the need of keeping health care workers alert to this issue

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Constitutively Nuclear FOXO3a Localization Predicts Poor Survival and Promotes Akt Phosphorylation in Breast Cancer

Background: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis. Methodology/Principal Findings: Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway. Conclusions/Significance: Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models. © 2010 Chen et al.published_or_final_versio

The role of P2 receptors in controlling infections by intracellular pathogens

A growing number of studies have demonstrated the importance of ATPe-signalling via P2 receptors as an important component of the inflammatory response to infection. More recent studies have shown that ATPe can also have a direct effect on infection by intracellular pathogens, by modulating membrane trafficking in cells that contain vacuoles that harbour intracellular pathogens, such as mycobacteria and chlamydiae. A conserved mechanism appears to be involved in controlling infection by both of these pathogens, as a role for phospholipase D in inducing fusion between lysosomes and the vacuoles has been demonstrated. Other P2-dependent mechanisms are most likely operative in the cases of pathogens, such as Leishmania, which survive in an acidic phagolysosomal-like compartment. ATPe may function as a ‘danger signal–that alerts the immune system to the presence of intracellular pathogens that damage the host cell, while different intracellular pathogens have evolved enzymes or other mechanisms to inhibit ATPe-mediated signalling, which should, thus, be viewed as virulence factors for these pathogens

The ‘Biophilic Organization’: An Integrative Metaphor for Corporate Sustainability

This paper proposes a new organizational metaphor, the ‘Biophilic Organization’, which aims to counter the bio-cultural disconnection of many organizations despite their espoused commitment to sustainability. This conceptual research draws on multiple disciplines such as evolutionary psychology and architecture to not only develop a diverse bio-cultural connection but to show how this connection tackles sustainability, in a holistic and systemic sense. Moreover, the paper takes an integrative view of sustainability, which effectively means that it embraces the different emergent tensions. Three specific tensions are explored: efficiency versus resilience, organizational versus personal agendas and isomorphism versus institutional change. In order to illustrate how the Biophilic Organization could potentially provide a synthesis strategy for such tensions, healthcare examples are drawn from the emerging fields of Biophilic Design in Singapore and Generative Design in the U.S.A. Finally, an example is provided which highlights how a Taoist cultural context has impacted on a business leader in China, to illustrative the significance of a transcendent belief system to such a bio-cultural narrative

Meaning of leprosy for people who have experienced treatment during the sulfonic and multidrug therapy periods

Objetivo:analizar los significados de la lepra para las personas que fueron tratadas en el período sulfónico y en el período de poliquimioterapia.Método:estudio de naturaleza cualitativa fundamentado en el abordaje histórico cultural de Vygotsky, el cual orientó la construcción y análisis de los datos. Fueron incluidos ocho entrevistados que ya tuvieron lepra y que realizaron tratamiento en el período sulfónico y de poliquimioterapia, siendo participantes del Movimiento de Reintegración de Personas Afectadas por la Lepra.Resultados:los significados fueron organizados en tres núcleos de significación: manchas en el cuerpo: alguna cosa está fuera de orden; ¿Lepra o enfermedad de Hansen?; y lepra a partir de la inserción en el Movimiento de Reintegración de Personas Afectadas por la Lepra. Conclusión: los significados de la lepra para las personas tratadas en los dos períodos apuntan para la construcción compleja de los mismos, indicando diferencias y semejanzas en los dos períodos. Los profesionales de la salud pueden contribuir para el cambio de significados, ya que estos son socialmente construidos y las transformaciones son continuas.Objetivo:analisar significados da hanseníase para as pessoas que foram tratadas no período sulfônico e no período da poliquimioterapia.Método:estudo de natureza qualitativa fundamentado na abordagem histórico-cultural de Vigotski, a qual orientou a construção e análise dos dados. Foram incluídos oito entrevistados que já tiveram hanseníase e que realizaram tratamento no período sulfônico e da poliquimioterapia, sendo participantes do Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Resultados:os significados foram organizados em três núcleos de significação: manchas no corpo: alguma coisa está fora de ordem; lepra ou hanseníase? e hanseníase a partir da inserção no Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Conclusão:os significados de hanseníase para pessoas tratadas nos dois períodos apontam para a construção complexa dos mesmos, indicando diferenças e semelhanças nos dois períodos. Os profissionais de saúde podem contribuir para a mudança de significados, pois esses são socialmente construídos e as transformações são contínuas.Objective: to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods.Method: qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy.Results: the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy.Conclusion: the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous