Herpes simplex virus type 1 ICP0 localizes in the stromal layer of infected rabbit corneas and resides predominantly in the cytoplasm and/or perinuclear region of rabbit keratocytes

Herpes stromal keratitis (HSK) results from the reactivation of herpes simplex virus type-1 (HSV-1) in the cornea. The subsequent corneal inflammation and neovascularization may lead to scarring and visual loss. The cellular and molecular mechanisms underlying HSK remain unknown. The presence of stromal HSV-1 viral proteins or antigens in the HSK cornea remains a subject of debate. It was recently reported that HSV-1 ICP0 rapidly diffuses out of infected rabbit corneas. To investigate further the presence of HSV-1 ICP0 in the infected cornea, particularly in the corneal stroma, ex vivo confocal microscopy was used to scan rabbit corneas infected with the virus ICP0–EYFP, an HSV-1 derivative (strain 17+) that expresses ICP0 fused to the enhanced yellow fluorescent protein (EYFP). These results demonstrate that ICP0 is expressed in the corneal epithelium and stromal cells (keratocytes) of infected rabbit corneas throughout acute infection. Furthermore, expression of ICP0–EYFP appears localized to punctate, granular deposits within stromal keratocytes, showing both a cytoplasmic and perinuclear localization. These findings provide new data demonstrating that anterior corneal keratocytes become infected and express ICP0 during acute HSV-1 infection

Peripheral (Deep) but Not Periventricular MRI White Matter Hyperintensities Are Increased in Clinical Vascular Dementia Compared to Alzheimer\u27s Disease

Background and purpose: Vascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer\u27s disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum. In this study, we sought to show whether the amount of WMH in deep white matter (dWMH), versus periventricular white matter (PVH), would aid in the distinction between VAD and AD, independent of age. Methods: Blinded semiquantitative ratings of WMH validated by objective quantitation of WMH volume from standardized MRI image acquisitions. PVH and dWMH were rated separately and independently by two different examiners using the Scheltens scale. Receiver operator characteristic (ROC) curves were generated using logistic regression to assess classification of VAD (13 patients) versus AD (129 patients). Clinical diagnoses were made in a specialty memory disorders clinic. Results: Using PVH rating alone, overall classification (area under the ROC curve, AUC) was 75%, due only to the difference in age between VAD and AD patients in our study and not PVH. In contrast, dWMH rating produced 86% classification accuracy with no independent contribution from age. A global Longstreth rating that combines dWMH and PVH gave an 88% AUC. Conclusions: Increased dWMH indicate a higher likelihood of VAD versus AD. Assessment of dWMH on MRI scans using Scheltens and Longstreth scales may aid the clinician in distinguishing the two conditions

Hyporheic invertebrates as bioindicators of ecological health in temporary rivers: a meta-analysis

Worldwide, many rivers cease flow and dry either naturally or owing to human activities such as water extraction. However, even when surface water is absent, diverse assemblages of aquatic invertebrates inhabit the saturated sediments below the river bed (hyporheic zone). In the absence of surface water or flow, biota of this zone may be sampled as an alternative to surface water-based ecological assessments. The potential of hyporheic invertebrates as ecological indicators of river health, however, is largely unexplored. We analysed hyporheic taxa lists from the international literature on temporary rivers to assess compositional similarity among broad-scale regions and sampling conditions, including the presence or absence of surface waters and flow, and the regional effect of hydrological phase (dry channel, non-flowing waters, surface flow) on richness. We hypothesised that if consistent patterns were found, then effects of human disturbances in temporary rivers may be assessable using hyporheic bioindicators. Assemblages differed geographically and by climate, but hydrological phase did not have a strong effect at the global scale. However, hyporheic assemblage composition within regions varied along a gradient of higher richness during wetter phases

Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106661/1/acel12170.pd

Acarbose improves health and lifespan in aging HET3 mice

To follow‐up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log‐rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%–11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2‐(2‐hydroxyphenyl) benzothiazole (HBX), and INT‐767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose‐control drugs in humans.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148418/1/acel12898.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148418/2/acel12898_am.pd

Costs and Consequences: Hepatitis C Seroprevalence in the Military and Its Impact on Potential Screening Strategies

UNLABELLED: Knowledge of the contemporary epidemiology of hepatitis C viral (HCV) infection among military personnel can inform potential Department of Defense screening policy. HCV infection status at the time of accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period 2007-2010. A cost model was developed from the perspective of the Department of Defense for a military applicant screening program. Return on investment was based on comparison between screening program costs and potential treatment costs avoided. The prevalence of HCV antibody-positive and chronic HCV infection at accession among younger recently deployed military personnel born after 1965 was 0.98/1000 (95% confidence interval 0.45-1.85) and 0.43/1000 (95% confidence interval 0.12-1.11), respectively. Among these, service-related incidence was low; 64% of infections were present at the time of accession. With no screening, the cost to the Department of Defense of treating the estimated 93 cases of chronic HCV cases from a single year\u27s accession cohort was $9.3 million. Screening with the HCV antibody test followed by the nucleic acid test for confirmation yielded a net annual savings and a$3.1 million dollar advantage over not screening. CONCLUSIONS: Applicant screening will reduce chronic HCV infection in the force, result in a small system costs savings, and decrease the threat of transfusion-transmitted HCV infection in the battlefield blood supply and may lead to earlier diagnosis and linkage to care; initiation of an applicant screening program will require ongoing evaluation that considers changes in the treatment cost and practice landscape, screening options, and the epidemiology of HCV in the applicant/accession and overall force populations

Hepatitis B Seroprevalence in the U.S. Military and its Impact on Potential Screening Strategies

INTRODUCTION: Knowledge of the contemporary epidemiology of hepatitis B virus (HBV) infection among military personnel can inform potential Department of Defense (DoD) screening policy and infection and disease control strategies. MATERIALS AND METHODS: HBV infection status at accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period from 2007 to 2010. A cost model was developed from the perspective of the Department of Defense for a program to integrate HBV infection screening of applicants for military service into the existing screening program of screening new accessions for vaccine-preventable infections. RESULTS: The prevalence of chronic HBV infection at accession was 2.3/1,000 (95% CI: 1.4, 3.2); most cases (16/21, 76%) identified after deployment were present at accession. There were 110 military service-related HBV infections identified. Screening accessions who are identified as HBV susceptible with HBV surface antigen followed by HBV surface antigen neutralization for confirmation offered no cost advantage over not screening and resulted in a net annual increase in cost of $5.78 million. However, screening would exclude as many as 514 HBV cases each year from accession. CONCLUSIONS: Screening for HBV infection at service entry would potentially reduce chronic HBV infection in the force, decrease the threat of transfusion-transmitted HBV infection in the battlefield blood supply, and lead to earlier diagnosis and linkage to care; however, applicant screening is not cost saving. Service-related incident infections indicate a durable threat, the need for improved laboratory-based surveillance tools, and mandate review of immunization policy and practice

Epistatic Module Detection for Case-Control Studies: A Bayesian Model with a Gibbs Sampling Strategy

The detection of epistatic interactive effects of multiple genetic variants on the susceptibility of human complex diseases is a great challenge in genome-wide association studies (GWAS). Although methods have been proposed to identify such interactions, the lack of an explicit definition of epistatic effects, together with computational difficulties, makes the development of new methods indispensable. In this paper, we introduce epistatic modules to describe epistatic interactive effects of multiple loci on diseases. On the basis of this notion, we put forward a Bayesian marker partition model to explain observed case-control data, and we develop a Gibbs sampling strategy to facilitate the detection of epistatic modules. Comparisons of the proposed approach with three existing methods on seven simulated disease models demonstrate the superior performance of our approach. When applied to a genome-wide case-control data set for Age-related Macular Degeneration (AMD), the proposed approach successfully identifies two known susceptible loci and suggests that a combination of two other loci—one in the gene SGCD and the other in SCAPER—is associated with the disease. Further functional analysis supports the speculation that the interaction of these two genetic variants may be responsible for the susceptibility of AMD. When applied to a genome-wide case-control data set for Parkinson's disease, the proposed method identifies seven suspicious loci that may contribute independently to the disease

Does the Establishment of Sustainable Use Reserves Affect Fire Management in the Humid Tropics?

Tropical forests are experiencing a growing fire problem driven by climatic change, agricultural expansion and forest degradation. Protected areas are an important feature of forest protection strategies, and sustainable use reserves (SURs) may be reducing fire prevalence since they promote sustainable livelihoods and resource management. However, the use of fire in swidden agriculture, and other forms of land management, may be undermining the effectiveness of SURs in meeting their conservation and sustainable development goals. We analyse MODIS derived hot pixels, TRMM rainfall data, Terra-Class land cover data, socio-ecological data from the Brazilian agro-census and the spatial extent of rivers and roads to evaluate whether the designation of SURs reduces fire occurrence in the Brazilian Amazon. Specifically, we ask (1) a. Is SUR location (i.e., de facto) or (1) b. designation (i.e. de jure) the driving factor affecting performance in terms of the spatial density of fires?, and (2), Does SUR creation affect fire management (i.e., the timing of fires in relation to previous rainfall)? We demonstrate that pre-protection baselines are crucial for understanding reserve performance. We show that reserve creation had no discernible impact on fire density, and that fires were less prevalent in SURs due to their characteristics of sparser human settlement and remoteness, rather than their status de jure. In addition, the timing of fires in relation to rainfall, indicative of local fire management and adherence to environmental law, did not improve following SUR creation. These results challenge the notion that SURs promote environmentally sensitive fire-management, and suggest that SURs in Amazonia will require special attention if they are to curtail future accidental wildfires, particularly as plans to expand the road infrastructure throughout the region are realised. Greater investment to support improved fire management by farmers living in reserves, in addition to other fire users, will be necessary to help ameliorate these threats