Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false- positive results occurred in the first year of testing. Of 425 HTLV- indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II- seropositive donors should be advised that they are infected with HTLV- I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.     

Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young‐adult Ts65Dn and disomic mice

Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer's disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. Although DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age‐related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3–7.5 months of age. Ts65Dn dams were maintained on a choline‐supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; post weaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, and brains were sectioned and immunolabeled for choline acetyltransferase (ChAT) or p75‐neurotrophin receptor (p75^NTR). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn‐unsupplemented mice displayed region‐ and immunolabel‐dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal‐diet choline supplementation attenuates some of the genotype‐dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. J. Comp. Neurol. 522:1390–1410, 2014. © 2013 Wiley Periodicals, Inc.     

Long-term perspective on wildfires in the western USA

Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in the American West and compare this record to independent fire-history data from historical records and fire scars. There has been a slight decline in burning over the past 3,000 y, with the lowest levels attained during the 20th century and during the Little Ice Age (LIA, ca. 1400–1700 CE [Common Era]). Prominent peaks in forest fires occurred during the Medieval Climate Anomaly (ca. 950–1250 CE) and during the 1800s. Analysis of climate reconstructions beginning from 500 CE and population data show that temperature and drought predict changes in biomass burning up to the late 1800s CE. Since the late 1800s , human activities and the ecological effects of recent high fire activity caused a large, abrupt decline in burning similar to the LIA fire decline. Consequently, there is now a forest “fire deficit” in the western United States attributable to the combined effects of human activities, ecological, and climate changes. Large fires in the late 20th and 21st century fires have begun to address the fire deficit, but it is continuing to grow.Forest fires in the western United States have been increasing in size (1) and possibly severity (2) for several decades. The increase in fire has prompted multiple investigations into both the causes (3, 4) and consequences of this shift for communities, ecosystems, and climate (5). Climate changes and human activities have both contributed to the observed changes in fire, but understanding the nature and magnitude of these impacts has been challenging first because there is substantial ecological heterogeneity and variability in terms of vegetation, soils, hydrology, topography, and other factors that affect fire regimes across the western United States, and second because most fire-history data come from recent decades and centuries when climate and human activities have both undergone rapid and unique transformations. As a result, studies tend to focus either on local ecological and anthropogenic factors that drive fire at fine scales (6, 7), or on climatic influences at broad scales (3, 4). Furthermore, the limited temporal scope of many fire-history studies does not provide adequate context for examining the joint impacts of climate and human activities on broad-scale, long-term fire regime changes. In addition, projections of future climate change and its ecosystem impacts place the expected changes well outside the range of variations in the past few centuries. Thus, coupling multi-decadal-to millennial-scale data on fire, climate changes, and human activities can reveal linkages among these components that are often missed in studies restricted to finer scales or fewer factors.Here we use sedimentary charcoal accumulation rates to construct variations in levels of burning for the past 3,000 y in the western United States (i.e., the West) and compare this record to independent fire-history data from historical records and fire scars. The long charcoal records enable identification of baseline shifts in fire regimes that cannot be detected with shorter records and allow us to view the nature and extent of human impacts on fire in a long-term context; this approach helps to distill the dominant patterns in fire activity across the West, but it does not reveal the important differences in fire controls and effects among vegetation types, ecoregions, or elevation gradients that exist at finer spatial scales (e.g., ref. 8).Our focus here is specifically on multi-decadal-to-centennial-scale variations in fire over the past few millennia and on the West as a whole. Climatic variations on this time scale are characterized by extended periods of persistent anomalies, such as the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA) (9, 10), which feature broad-scale (i.e., across the whole of the western United States) anomalies of both surface climates and atmospheric circulation (10). We use temperature (10), drought (9), and population (11) data to compare with the fire-history reconstructions. We also construct a simple statistical model for predicting biomass burning from the temperature and drought data. Our analysis builds on the rich historical narratives of fire in the western United States (12) as well as on many more detailed but shorter broad-scale studies (4, 13, 14). The results illustrate the importance of climate in explaining the variations in fire over time, and show the development of a 20th century “fire deficit” related to the combined effects of fire exclusion, land-use change, and ongoing climate change.     

Integrated implementation of programs targeting neglected tropical diseases through preventive chemotherapy: identifying best practices to roll out programs at national scale

In 2006 the U.S. Agency for International Development (USAID) established the Neglected Tropical Disease (NTD) Control Program to support national governments in developing successful, cost-efficient NTD programs that integrate disease-specific programs into coordinated national initiatives, in accord with the World Health Organization recommendations. A 3-stage "roll-out package" has been developed for effectively integrating and scaling up such programs to full-national scale. Stage-1 lays the groundwork-identifying NTD leadership within the Ministry of Health, conducting a national Situation Analysis, formulating a multiyear Plan of Action, and undertaking a funding gap analysis. Stage-2 focuses on scaling up the integrated NTD program-convening national stakeholder meetings, developing annual work plans, carrying out disease mapping, and establishing monitoring and evaluation activities. Stage-3 aims at ensuring effective management-identifying clear roles and responsibilities for partners, and creating a central coordinating mechanism. Assessment and reassessment of these complex NTD programs that target literally billions of people are essential to establish "best practice" strategies for long-term public health success.     

Plasma cytokines in polycythemia vera: Phenotypic correlates,prognostic relevance,and comparison with myelofibrosis

Plasma cytokine milieu is abnormal in primary myelofibrosis (PMF) and correlates with disease phenotype and prognosis. In this study, we show that several plasma cytokines are also abnormally expressed in polycythemia vera (PV; n = 65), compared to normal controls (n = 35), but with a significantly different pattern than that of PMF (n = 127). Direct phenotypic correlation in PV included levels of IL‐12 with hematocrit; IL‐1b, IL‐2, IL‐7, FGF‐b, and HGF with leukocytosis; and IFN‐α and IFN‐γ with thrombocytosis. In univariate analysis, levels of 13 cytokines (out of 30 analyzed) correlated with survival but only MIP‐1β remained significant on multivariable analysis that included the other cytokines as covariates. Increased level of MIP‐1β (P < 0.01), older age (P < 0.01), and leukocytosis (P = 0.03) maintained their association with shortened survival, on multivariable analysis. This study provides preliminary observations that warrant a larger scale study and suggests the value of plasma cytokines as prognostic biomarkers in PV. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.     

The impact of periodontitis on oral health‐related quality of life: a review of the evidence from observational studies

Modern population based oral health management requires a complete understanding of the impact of disease in order to provide efficient and effective oral health care and guidance. Periodontitis is an important cause of tooth loss and has been shown to be associated with a number of systemic conditions. The impact of oral conditions and disorders on quality of life has been extensively studied. However, the impact of periodontitis on quality of life has received less attention. This review summarizes the literature on the impact of periodontitis on oral health‐related quality of life (OHRQoL). Relevant publications were identified after searching the MEDLINE and EMBASE electronic databases. Screening of titles and abstracts and data extraction was conducted. Only observational studies were included in this review. Most of the reviewed studies reported a negative impact of periodontitis on OHRQoL. However, the reporting standards varied across studies. Moreover, most of the studies were conducted in developed countries.