Regional vitiligo induced by imiquimod treatment for in-transit melanoma metastases

Imiquimod is a topical immunomodulator used for the treatment of viral warts and superficial basal cell carcinoma and as an emerging therapy for lentigo maligna and cutaneous melanoma metastases. Vitiligo-like depigmentation has been described as a local adverse effect of topical imiquimod therapy for melanoma1 and at distant sites in patients treated with combination topical monobenzone-imiquimod for metastatic melanoma.2 We present a case in which topical imiquimod resulted in both the resolution of in-transit metastatic melanoma and the depigmentation of local and regional skin, suggesting a regional lymphatic effect of this localized topical treatment

Genetic Structure of Faucet Snail, Bithynia tentaculata Populations in North America, Based on Microsatellite Markers

Bithynia tentaculata is believed to have been extirpated from North America during the last glacial maximum. It was reintroduced into North America via the Great Lakes basin in the 1800’s and has recently been expanding its geographic range. This snail serves as intermediate host for three trematodes that cause extensive recurring morbidity and mortality events in migratory water birds along the Mississippi River. Using twelve microsatellite loci for ~200 individual snails from 11populations in North America and Europe, we examined one of the three major geographic regions from which founding populations into the Great Lakes typically originate. Our data supports a single colonization of North America into the Great Lakes Basin followed by subsequent introduction events from the Great Lakes to other large watersheds in North America. However, additional watersheds in Europe require sampling to confirm this result. No populations with genetic signatures indicative of North American glacial relics were found. The initial invasion of North America was likely not from the Ponto-Caspian basin, the usual source of freshwater invasive species to the Laurentian Great Lake

Research Report: Radicchio Cultivar Performance in New Hampshire

Radicchio (Cichorium intybus var. latifolium) is grown widely throughout Europe, especially northern Italy. In addition to having interesting color and flavor profiles, they are rich in phenolics and other bioactive compounds. While increasingly popular as a niche vegetable in the region, there is little research-based information to guide growers. The New England growing climate is very different from that of major production regions, and it presents unique challenges. There is tremendous phenotypic variation among and within groups and cultivars. The availability of varieties to commercial growers in the U.S. has expanded greatly, but there remains a need for reliable regionally relevant information about performance of these varieties. In 2022 and 2023, we evaluated over 30 varieties in a replicated trial. We also planted three varieties at four different dates to evaluate the effects of planting date on harvest maturity and marketable yields. In the current research report, we describe the results of these experiments

Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone

ABSTRACT Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs

Rate of telomere shortening and cardiovascular damage: a longitudinal study in the 1946 British Birth Cohort.

AIM: Cross-sectional studies reported associations between short leucocyte telomere length (LTL) and measures of vascular and cardiac damage. However, the contribution of LTL dynamics to the age-related process of cardiovascular (CV) remodelling remains unknown. In this study, we explored whether the rate of LTL shortening can predict CV phenotypes over 10-year follow-up and the influence of established CV risk factors on this relationship. METHODS AND RESULTS: All the participants from the MRC National Survey of Health and Development (NSHD) with measures of LTL and traditional CV risk factors at 53 and 60-64 years and common carotid intima-media thickness (cIMT), cardiac mass and left ventricular function at 60-64 years were included. LTL was measured by real-time polymerase chain reaction and available at both time points in 1033 individuals. While LTL at 53 years was not linked with any CV phenotype at 60-64 years, a negative association was found between LTL and cIMT at 60-64 years (β = -0.017, P = 0.015). However, the strongest association was found between rate of telomere shortening between 53 and 60-64 years and values of cIMT at 60-64 years (β = -0.020, P = 0.006). This association was not affected by adjustment for traditional CV risk factors. Cardiac measurements were not associated with cross-sectional or longitudinal measures of LTL. CONCLUSION: These findings suggest that the rate of progression of cellular ageing in late midlife (reflected by the rate of LTL attrition) relates to vascular damage, independently from contribution of CV risk factor exposure

Concert recording 2018-05-14

[Track 1]. Impresiones de la Puna / Alberto E. Ginastera -- [Track 2]. Sextet for piano and woodwind quintet FP 100 / Francis Poulenc -- [Track 3]. Cantata. Solitudine Avvenne / Alessandro Scarlatti -- [Track 4]. Suite for flute and jazz piano trio / Claude Bolling

MADNESS: A Multiresolution, Adaptive Numerical Environment for Scientific Simulation

MADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics

The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer

BACKGROUND: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. METHODS: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic and 30,054 dizygotic same sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability. RESULTS: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability (heritability=58% (95% CI 52%–63%) of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. CONCLUSIONS: Results from the population based twin cohort, indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age IMPACT: Findings impact the search for genetic and epigenetic markers and frame prevention efforts

Analysis of System Training Impact for Major Defense Acquisition Programs (MDAPs): Training Systems Acquisition

This work was conducted by the Institute for Defense Analyses (IDA) under contract W91WAW-09-C-0003, Task BE-2-3376, “Analysis of Systems Training Impact for Major Defense Acquisition Programs,” for the Director, Training Readiness and Strategy, in the Office of the Under Secretary of Defense for Personnel and Readiness.W91WAW-09-C-0003, Task BE-2-337

Mental health of adults in Ireland during the first year of the COVID-19 pandemic: Results from a nationally representative, longitudinal study

No abstract available