K13 blocks KSHV lytic replication and deregulates vIL6 nad hIL6 expression: A model of lytic replication induced clonal selection in viral oncogenesis

Background. Accumulating evidence suggests that dysregulated expression of lytic genes plays an important role in KSHV (Kaposi's sarcoma associated herpesvirus) tumorigenesis. However, the molecular events leading to the dysregulation of KSHV lytic gene expression program are incompletely understood. Methodoloxy/Principal Findings. We have studied the effect of KSHV-encoded latent protein vFLIP K13, a potent activator of the NF-κB pathway, on lytic reactivation of the virus. We demonstrate that K13 antagonizes RTA, the KSHV lytic-regulator, and effectively blocks the expression of lytic proteins, production of infectious virions and death of the infected cells. Induction of lytic replication selects for clones with increased K13 expression and NF-κB activity, while siRNA-mediated silencing of K13 induces the expression of lytic genes. However, the suppressive effect of K13 on RTA-induced lytic genes is not uniform and it falls to block RTA-induced viral IL6 secretion and cooperates with RTA to enhance cellular IL-6 production, thereby dysregulating the lytic gene expression program. Conclusions/Significance. Our results support a model in which ongoing KSHV, lytic replication selects for clones with progressively higher levels of K13 expression and NF-κB activity, which in turn drive KSHV tumorigenesis by not only directly stimulating cellular survival and proliferation, but also indirectly by dysregulating the viral lytic gene program and allowing non-lytic production of growth-promoting viral and cellular genes. Lytic Replication-Induced Clonal Selection (LyRICS) may represent a general mechanism in viral oncogenesis. 2007 Zhao et al

Tendência da mortalidade por câncer do útero no Município de São Paulo entre 1980 e 1999 Mortality trends from uterine cervical cancer in the city of São Paulo from 1980 to 1999

O câncer do colo do útero apresenta grande incidência em algumas cidades brasileiras e considerável mortalidade em países em desenvolvimento, não obstante a disponibilidade já antiga de teste de rastreamento. O presente estudo visou avaliar a tendência da mortalidade por câncer de colo do útero, de corpo do útero e por câncer do útero não especificado, no Município de São Paulo, entre 1980 e 1999, por meio do exame das taxas brutas, idade-específica e ajustadas por idade. Os resultados mostraram discreta redução da mortalidade por câncer do colo do útero, queda da mortalidade por câncer de útero não especificado e aumento da mortalidade por câncer do corpo do útero. Conclui-se que a queda da mortalidade por câncer do útero não especificado sinaliza uma melhora na precisão do diagnóstico clínico e na qualidade do preenchimento do atestado de óbito, e indica aumento de cobertura do teste de Papanicolaou.<br>Uterine cervical cancer shows a higher incidence in some Brazilian cities. It is a common cause of death in women from developing countries, despite the longstanding availability of an effective screening test, the Pap smear. This study aimed to evaluate the temporal trends of crude, age-adjusted, and age-specific mortality rates from cervical cancer, endometrial cancer, and cancer of the uterus not otherwise specified (NOS) in the city of São Paulo from 1980 to 1999. Results showed a slight reduction in cervical cancer rates, a decrease in NOS uterine cancer rates, and an increase in endometrial cancer mortality rates. The fall in mortality from NOS uterine cancer indicates an improvement in diagnostic accuracy and quality of information on death certificates and may point to an increase in coverage of cervical cancer screening using the Pap smear

Emerging Adulthood as a Critical Stage in the Life Course

Book Summary: This handbook synthesizes and analyzes the growing knowledge base on life course health development (LCHD) from the prenatal period through emerging adulthood, with implications for clinical practice and public health. It presents LCHD as an innovative field with a sound theoretical framework for understanding wellness and disease from a lifespan perspective, replacing previous medical, biopsychosocial, and early genomic models of health. Interdisciplinary chapters discuss major health concerns (diabetes, obesity), important less-studied conditions (hearing, kidney health), and large-scale issues (nutrition, adversity) from a lifespan viewpoint. In addition, chapters address methodological approaches and challenges by analyzing existing measures, studies, and surveys. The book concludes with the editors’ research agenda that proposes priorities for future LCHD research and its application to health care practice and health policy. Topics featured in the Handbook include: The prenatal period and its effect on child obesity and metabolic outcomes. Pregnancy complications and their effect on women’s cardiovascular health. A multi-level approach for obesity prevention in children. Application of the LCHD framework to autism spectrum disorder. Socioeconomic disadvantage and its influence on health development across the lifespan. The importance of nutrition to optimal health development across the lifespan. The Handbook of Life Course Health Development is a must-have resource for researchers, clinicians/professionals, and graduate students in developmental psychology/science; maternal and child health; social work; health economics; educational policy and politics; and medical law as well as many interrelated subdisciplines in psychology, medicine, public health, mental health, education, social welfare, economics, sociology, and law

Renal transplantation in autosomal dominant polycystic kidney disease

In patients with autosomal dominant polycystic kidney disease (ADPKD) evaluated for kidney transplantation, issues related to native nephrectomy, cystic liver involvement, screening for intracranial aneurysms and living-related kidney donation deserve special consideration. Prophylactic native nephrectomy is restricted to patients with a history of cyst infection or recurrent haemorrhage or to those in whom space must be made to implant the graft. Patients with liver involvement require pretransplant imaging. Selection of patients for pretransplant screening of intracranial aneurysms should follow the general recommendations for patients with ADPKD. In living related-donor candidates aged <30 years and at-risk of ADPKD, molecular genetic testing should be carried out when ultrasonography and MRI findings are normal or equivocal. After kidney transplantation, patient and graft survival rates are excellent and the volume of native kidneys decreases. However, liver cysts continue to grow and treatment with a somatostatin analogue should be considered in patients with massive cyst involvement. Cerebrovascular events have a marginal effect on post-transplant morbidity and mortality. An increased risk of new-onset diabetes mellitus and nonmelanoma skin cancers has been reported, but several studies have challenged these findings. Finally, no data currently support the preferential use of mammalian target of rapamycin inhibitors as immunosuppressive agents in transplant recipients with ADPKD