Dengue Deaths in Puerto Rico: Lessons Learned from the 2007 Epidemic

Dengue is a major public health problem in the tropics and subtropics; an estimated 50 million cases occur annually and 40 percent of the world's population lives in areas with dengue virus (DENV) transmission. Dengue has a wide range of clinical presentations from an undifferentiated acute febrile illness, classic dengue fever, to severe dengue (i.e., dengue hemorrhagic fever or dengue shock syndrome). About 5% of patients develop severe dengue, which is more common with second or subsequent infections. No vaccines are available to prevent dengue, and there are no specific antiviral treatments for patients with dengue. However, early recognition of shock and intensive supportive therapy can reduce risk of death from ∼10% to less than 1% among severe dengue cases. Reviewing dengue deaths is one means to identify issues in clinical management. These findings can be used to develop healthcare provider education to minimize dengue morbidity and mortality

cDNA Immunization of Mice with Human Thyroglobulin Generates Both Humoral and T Cell Responses: A Novel Model of Thyroid Autoimmunity

Thyroglobulin (Tg) represents one of the largest known self-antigens involved in autoimmunity. Numerous studies have implicated it in triggering and perpetuating the autoimmune response in autoimmune thyroid diseases (AITD). Indeed, traditional models of autoimmune thyroid disease, experimental autoimmune thyroiditis (EAT), are generated by immunizing mice with thyroglobulin protein in conjunction with an adjuvant, or by high repeated doses of Tg alone, without adjuvant. These extant models are limited in their experimental flexibility, i.e. the ability to make modifications to the Tg used in immunizations. In this study, we have immunized mice with a plasmid cDNA encoding the full-length human Tg (hTG) protein, in order to generate a model of Hashimoto's thyroiditis which is closer to the human disease and does not require adjuvants to breakdown tolerance. Human thyroglobulin cDNA was injected and subsequently electroporated into skeletal muscle using a square wave generator. Following hTg cDNA immunizations, the mice developed both B and T cell responses to Tg, albeit with no evidence of lymphocytic infiltration of the thyroid. This novel model will afford investigators the means to test various hypotheses which were unavailable with the previous EAT models, specifically the effects of hTg sequence variations on the induction of thyroiditis

The Ionizing Radiation-Induced Bystander Effect: Evidence, Mechanism, and Significance

It has long been considered that the important biological effects of ionizing radiation are a direct consequence of unrepaired or misrepaired DNA damage occurring in the irradiated cells. It was presumed that no effect would occur in cells in the population that receive no direct radiation exposure. However, in vitro evidence generated over the past two decades has indicated that non-targeted cells in irradiated cell cultures also experience significant biochemical and phenotypic changes that are often similar to those observed in the targeted cells. Further, nontargeted tissues in partial body-irradiated rodents also experienced stressful effects, including oxidative and oncogenic effects. This phenomenon, termed the “bystander response,” has been postulated to impact both the estimation of health risks of exposure to low doses/low fluences of ionizing radiation and the induction of second primary cancers following radiotherapy. Several mechanisms involving secreted soluble factors, oxidative metabolism, gap-junction intercellular communication, and DNA repair, have been proposed to regulate radiation-induced bystander effects. The latter mechanisms are major mediators of the system responses to ionizing radiation exposure, and our knowledge of the biochemical and molecular events involved in these processes is reviewed in this chapter

The effectiveness of antenatal care programmes to reduce infant mortality and preterm birth in socially disadvantaged and vulnerable women in high-income countries: a systematic review

Background: Infant mortality has shown a steady decline in recent years but a marked socioeconomic gradient persists. Antenatal care is generally thought to be an effective method of improving pregnancy outcomes, but the effectiveness of specific antenatal care programmes as a means of reducing infant mortality in socioeconomically disadvantaged and vulnerable groups of women has not been rigorously evaluated.Methods: We conducted a systematic review, focusing on evidence from high income countries, to evaluate the effectiveness of alternative models of organising or delivering antenatal care to disadvantaged and vulnerable groups of women vs. standard antenatal care. We searched Medline, Embase, Cinahl, PsychINFO, HMIC, CENTRAL, DARE, MIDIRS and a number of online resources to identify relevant randomised and observational studies. We assessed effects on infant mortality and its major medical causes (preterm birth, congenital anomalies and sudden infant death syndrome (SIDS)).Results: We identified 36 distinct eligible studies covering a wide range of interventions, including group antenatal care, clinic-based augmented care, teenage clinics, prenatal substance abuse programmes, home visiting programmes, maternal care coordination and nutritional programmes. Fifteen studies had adequate internal validity: of these, only one was considered to demonstrate a beneficial effect on an outcome of interest. Six interventions were considered 'promising'.Conclusions: There was insufficient evidence of adequate quality to recommend routine implementation of any of the programmes as a means of reducing infant mortality in disadvantaged/vulnerable women. Several interventions merit further more rigorous evaluation

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe