An Opsonophagocytic Killing Assay for the Evaluation of Group A Streptococcus Vaccine Antisera

Group A Streptococcus (GAS) is a major cause of global mortality, yet there are no licensed GAS vaccines. Vaccine progress has been hampered, in part, by a lack of standardized assays able to quantify antibody function in test antisera. The most widely used assay was developed over 50 years ago by Rebecca Lancefield and relies on human whole blood as a source of complement and neutrophils. Recently, an opsonophagocytic killing (OPK) assay has been developed for GAS by adapting the OPK methods utilized in Streptococcus pneumoniae vaccine testing. This assay uses dimethylformamide (DMF)-differentiated human promyelocytic leukemia cells (HL-60 cells) as a source of neutrophils and baby rabbit complement, thus removing the major sources of variation in the Lancefield assays. This protocol outlines methods for performing a GAS OPK assay including titering test sera to generate an opsonic index. This in vitro assay could aid in selecting vaccine candidates by demonstrating whether candidate-induced antibodies lead to complement deposition and opsonophagocytic killing

HIV vaccine: it may take two to tango, but no party time yet

A press conference on Thursday September 24 in Bangkok, Thailand, released data that an experimental vaccine provided mild protection against HIV-1 infection. This is the first positive signal of any degree of vaccine efficacy in humans, more than a quarter-century after scientists discovered the virus that causes AIDS. The research was conducted by a team including Thai researchers, the U.S. Army and the U.S. National Institutes of Health. The RV144 Phase III clinical trial, which began in 2003, had been disparaged by many critics as a waste of time and money because each of the two components had been shown to produce no benefit as individual vaccines and because the scientific rationales behind the immunogens were just wrong. It was nevertheless speculated that using them together in the prime-boost scenario could be more effective, with the aim to induce heightened CD4+ cellular immune responses against the viral Envelope protein. This optimism seems to have been validated. In fact, this would not be the first time that the discovery of an effective vaccine relied as much on serendipity as opposed to scientific rationale. On the other hand, many questions remain about the RV144 trial, and these issues will be addressed in this editorial

Nodular melanoma presenting with rapid progression and widespread metastases: a case report

<p>Abstract</p> <p>Introduction</p> <p>Melanoma is responsible for 1% to 2% of all cancer deaths around the world. Nodular melanoma often carries a poor prognosis because of no prodromal radial growth phase, early distant metastasis and significant tumor volume.</p> <p>Case presentation</p> <p>We present a case of progressive melanoma. A 51-year-old man was admitted to our hospital with dyspnea and skin lesions. These were multiple, dark colored, firm, and nodular and varied in size. He was diagnosed with melanoma. Temozolomide was administered, but he died of respiratory failure within a week after diagnosis.</p> <p>Conclusion</p> <p>Nodular melanoma tends to spread rapidly and eventually metastasize to vital organs. It may be fatal within months of recognition.</p

The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors.Methods: A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes ( birth weight, small for gestational age and preterm births), in a two-level hierarchical model.Results: We found effects of both individual ( education, race, prenatal care index) and area-based ( median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income.Conclusion: Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health.This work is supported by the Harvard Environmental Protection Agency (EPA) Center, Grants R827353 and R-832416, and National Institute for Environmental Health Science (NIEHS) ES-0002

Visual recovery in a patient with total hyphema, neovascular glaucoma, long-standing retinal detachment and no light perception vision: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a patient with total hyphema, neovascular glaucoma, long-standing retinal detachment and no light perception vision, who regained counting fingers vision with complete regression of neovascularization following anterior chamber washout, intravitreal bevacizumab, pars plana vitrectomy, and silicone oil placement. This represents a rare case in which a patient with no light perception vision was able to regain functional vision.</p> <p>Case presentation</p> <p>A 63-year-old Caucasian man with a 55-year history of long-standing retinal detachment after trauma presented to our facility with pain and redness, a total hyphema, no light perception vision and an intraocular pressure of 60 mmHg (right eye). He had a history of diabetes mellitus and coronary artery disease. Following anterior chamber washout, he was found to have neovascular glaucoma, for which intravitreal bevacizumab was administered. After washout and intraocular pressure control, his visual acuity improved to light perception. He subsequently underwent vitrectomy, membrane peeling, endolaser and silicone oil placement to reattach his retina, and then a second retinal reattachment procedure. Following these procedures, he had visual recovery to counting fingers vision in his right eye at five metres, complete regression of neovascularization, and intraocular pressure of 10 to 12 mmHg on one antiglaucoma medication.</p> <p>Conclusion</p> <p>Functional vision can be regained despite long-standing retinal detachment.</p

Matched Ascertainment of Informative Families for Complex Genetic Modelling

Family data are used extensively in quantitative genetic studies to disentangle the genetic and environmental contributions to various diseases. Many family studies based their analysis on population-based registers containing a large number of individuals composed of small family units. For binary trait analyses, exact marginal likelihood is a common approach, but, due to the computational demand of the enormous data sets, it allows only a limited number of effects in the model. This makes it particularly difficult to perform joint estimation of variance components for a binary trait and the potential confounders. We have developed a data-reduction method of ascertaining informative families from population-based family registers. We propose a scheme where the ascertained families match the full cohort with respect to some relevant statistics, such as the risk to relatives of an affected individual. The ascertainment-adjusted analysis, which we implement using a pseudo-likelihood approach, is shown to be efficient relative to the analysis of the whole cohort and robust to mis-specification of the random effect distribution

Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1

The Natural History of Trachoma Infection and Disease in a Gambian Cohort with Frequent Follow-Up

Trachoma is an infectious disease of the eye that causes blindness in many of the poorest parts of the world. In this paper, we use a novel statistical approach to estimate the characteristics of this disease among people living in The Gambia who were examined every 2 weeks over a 6-month period. We found that the typical duration of infection with Chlamydia trachomatis and of clinically active disease were significantly longer than previously estimated. We tested different hypotheses about the natural history of trachoma that explain the relationship between infection and disease observed in the field. We also confirmed that disease lasts significantly longer among young children under 5 years old compared with older children and adults, even after accounting for high rates of re-infection in this age group, consistent with the development of immunity with age. The long duration of infection, especially among younger children, contributes to the persistence and gradual return of trachoma after community-wide treatment with azithromycin. This implies the need for high treatment coverage if infection is to be eliminated from a community, even where the return of infection after treatment is seen to be slow