Chronic non-freezing cold injury results in neuropathic pain due to a sensory neuropathy

Non-freezing cold injury develops after sustained exposure to cold temperatures, resulting in tissue cooling but not freezing. This can result in persistent sensory disturbance of the hands and feet including numbness, paraesthesia and chronic pain. Both vascular and neurological aetiologies of this pain have been suggested but remain unproven. We prospectively approached patients referred for clinical assessment of chronic pain following non-freezing cold injury between 12 February 2014 and 30 November 2016. Of 47 patients approached, 42 consented to undergo detailed neurological evaluations including: questionnaires to detail pain location and characteristics, structured neurological examination, quantitative sensory testing, nerve conduction studies and skin biopsy for intraepidermal nerve fibre assessment. Of the 42 study participants, all had experienced non-freezing cold injury while serving in the UK armed services and the majority were of African descent (76.2%) and male (95.2%). Many participants reported multiple exposures to cold. The median time between initial injury and referral was 3.72 years. Pain was principally localized to the hands and the feet, neuropathic in nature and in all study participants associated with cold hypersensitivity. Clinical examination and quantitative sensory testing were consistent with a sensory neuropathy. In all cases, large fibre nerve conduction studies were normal. The intraepidermal nerve fibre density was markedly reduced with 90.5% of participants having a count at or below the 0.05 centile of published normative controls. Using the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain grading for neuropathic pain, 100% had probable and 95.2% definite neuropathic pain. Chronic non-freezing cold injury is a disabling neuropathic pain disorder due to a sensory neuropathy. Why some individuals develop an acute painful sensory neuropathy on sustained cold exposure is not yet known, but individuals of African descent appear vulnerable. Screening tools, such as the DN4 questionnaire, and treatment algorithms for neuropathic pain should now be used in the management of these patients

RBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory pathways

RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Rbm47-IKO mice exhibited increased proliferation and abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapted to radiation injury and were protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and developmental genes. Furthermore, Rbm47-IKO mice were protected against colitis-associated cancer. By contrast, aged Rbm47-IKO mice developed spontaneous polyposis, and Rbm47-IKO ApcMin/+ mice manifested an increased intestinal polyp burden. RBM47 mRNA was decreased in human colorectal cancer versus paired normal tissue, along with alternative splicing of tight junction protein 1 mRNA. Public databases revealed stage-specific reduction in RBM47 expression in colorectal cancer associated independently with decreased overall survival. These findings implicate RBM47 as a cell-intrinsic modifier of intestinal growth, inflammatory, and tumorigenic pathways

Sublittoral soft bottom communities and diversity of Mejillones Bay in northern Chile (Humboldt Current upwelling system)

The macrozoobenthos of Mejillones Bay (23°S; Humboldt Current) was quantitatively investigated over a 7-year period from austral summer 1995/1996 to winter 2002. About 78 van Veen grab samples taken at six stations (5, 10, 20 m depth) provided the basis for the analysis of the distribution of 60 species and 28 families of benthic invertebrates, as well as of their abundance and biomass. Mean abundance (2,119 individuals m-2) was in the same order compared to a previous investigation; mean biomass (966 g formalin wet mass m-2), however, exceeded prior estimations mainly due to the dominance of the bivalve Aulacomya ater. About 43% of the taxa inhabited the complete depth range. Mean taxonomic Shannon diversity (H', Log e) was 1.54 ± 0.58 with a maximum at 20 m (1.95 ± 0.33); evenness increased with depth. The fauna was numerically dominated by carnivorous gastropods, polychaetes and crustaceans (48%). About 15% of the species were suspensivorous, 13% sedimentivorous, 11% detritivorous, 7% omnivorous and 6% herbivorous. Cluster analyses showed a significant difference between the shallow and the deeper stations. Gammarid amphipods and the polychaete family Nephtyidae characterized the 5-mzone, the molluscs Aulacomya ater, Mitrella unifasciata and gammarids the intermediate zone, while the gastropod Nassarius gayi and the polychaete family Nereidae were most prominent at the deeper stations. The communities of the three depth zones did not appear to be limited by hypoxia during non-El Niño conditions. Therefore, no typical change in community structure occurred during El Niño 1997–1998, in contrast to what was observed for deeper faunal assemblages and hypoxic bays elsewhere in the coastal Humboldt Current system

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

Exploring the relationship between video game expertise and fluid intelligence

Hundreds of millions of people play intellectually-demanding video games every day. What does individual performance on these games tell us about cognition? Here, we describe two studies that examine the potential link between intelligence and performance in one of the most popular video games genres in the world (Multiplayer Online Battle Arenas: MOBAs). In the first study, we show that performance in the popular MOBA League of Legends' correlates with fluid intelligence as measured under controlled laboratory conditions. In the second study, we also show that the age profile of performance in the two most widely-played MOBAs (League of Legends and DOTA II) matches that of raw fluid intelligence. We discuss and extend previous videogame literature on intelligence and videogames and suggest that commercial video games can be useful as 'proxy' tests of cognitive performance at a global population level

Non-participation in population-based disease prevention programs in general practice

<p>Abstract</p> <p>Background</p> <p>The number of people with a chronic disease will strongly increase in the next decades. Therefore, prevention of disease becomes increasingly important. The aim of this systematic review was to identify factors that negatively influence participation in population-based disease prevention programs in General Practice and to establish whether the program type is related to non-participation levels.</p> <p>Methods</p> <p>We conducted a systematic review in Pubmed, EMBASE, CINAHL and PsycINFO, covering 2000 through July 6th 2012, to identify publications including information about characteristics of non-participants or reasons for non-participation in population-based disease prevention programs in General Practice.</p> <p>Results</p> <p>A total of 24 original studies met our criteria, seven of which focused on vaccination, eleven on screening aimed at early detection of disease, and six on screening aimed at identifying high risk of a disease, targeting a variety of diseases and conditions. Lack of personal relevance of the program, younger age, higher social deprivation and former non-participation were related to actual non-participation. No differences were found in non-participation levels or factors related to non-participation between the three program types. The large variation in non-participation levels within the program types may be partly due to differences in recruitment strategies, with more active, personalized strategies resulting in higher participation levels compared to an invitation letter.</p> <p>Conclusions</p> <p>There is still much to be gained by tailoring strategies to improve participation in those who are less likely to do so, namely younger individuals, those living in a deprived area and former non-participants. Participation may increase by applying more active recruitment strategies.</p

Herbivore Preference for Native vs. Exotic Plants: Generalist Herbivores from Multiple Continents Prefer Exotic Plants That Are Evolutionarily Naïve

Enemy release and biotic resistance are competing, but not mutually exclusive, hypotheses addressing the success or failure of non-native plants entering a new region. Enemy release predicts that exotic plants become invasive by escaping their co-adapted herbivores and by being unrecognized or unpalatable to native herbivores that have not been selected to consume them. In contrast, biotic resistance predicts that native generalist herbivores will suppress exotic plants that will not have been selected to deter these herbivores. We tested these hypotheses using five generalist herbivores from North or South America and nine confamilial pairs of native and exotic aquatic plants. Four of five herbivores showed 2.4–17.3 fold preferences for exotic over native plants. Three species of South American apple snails (Pomacea sp.) preferred North American over South American macrophytes, while a North American crayfish Procambarus spiculifer preferred South American, Asian, and Australian macrophytes over North American relatives. Apple snails have their center of diversity in South America, but a single species (Pomacea paludosa) occurs in North America. This species, with a South American lineage but a North American distribution, did not differentiate between South American and North American plants. Its preferences correlated with preferences of its South American relatives rather than with preferences of the North American crayfish, consistent with evolutionary inertia due to its South American lineage. Tests of plant traits indicated that the crayfish responded primarily to plant structure, the apple snails primarily to plant chemistry, and that plant protein concentration played no detectable role. Generalist herbivores preferred non-native plants, suggesting that intact guilds of native, generalist herbivores may provide biotic resistance to plant invasions. Past invasions may have been facilitated by removal of native herbivores, introduction of non-native herbivores (which commonly prefer native plants), or both

Ecological Implications of Extreme Events: Footprints of the 2010 Earthquake along the Chilean Coast

Deciphering ecological effects of major catastrophic events such as earthquakes, tsunamis, volcanic eruptions, storms and fires, requires rapid interdisciplinary efforts often hampered by a lack of pre-event data. Using results of intertidal surveys conducted shortly before and immediately after Chile's 2010 Mw 8.8 earthquake along the entire rupture zone (ca. 34–38°S), we provide the first quantification of earthquake and tsunami effects on sandy beach ecosystems. Our study incorporated anthropogenic coastal development as a key design factor. Ecological responses of beach ecosystems were strongly affected by the magnitude of land-level change. Subsidence along the northern rupture segment combined with tsunami-associated disturbance and drowned beaches. In contrast, along the co-seismically uplifted southern rupture, beaches widened and flattened increasing habitat availability. Post-event changes in abundance and distribution of mobile intertidal invertebrates were not uniform, varying with land-level change, tsunami height and coastal development. On beaches where subsidence occurred, intertidal zones and their associated species disappeared. On some beaches, uplift of rocky sub-tidal substrate eliminated low intertidal sand beach habitat for ecologically important species. On others, unexpected interactions of uplift with man-made coastal armouring included restoration of upper and mid-intertidal habitat seaward of armouring followed by rapid colonization of mobile crustaceans typical of these zones formerly excluded by constraints imposed by the armouring structures. Responses of coastal ecosystems to major earthquakes appear to vary strongly with land-level change, the mobility of the biota and shore type. Our results show that interactions of extreme events with human-altered shorelines can produce surprising ecological outcomes, and suggest these complex responses to landscape alteration can leave lasting footprints in coastal ecosystems

Morphological predictors of BRCA1 germline mutations in young women with breast cancer

BACKGROUND: Knowing a young woman with newly diagnosed breast cancer has a germline BRCA1 mutation informs her clinical management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer morphology and hormone receptor status data.METHODS: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation.RESULTS: The probability of being a BRCA1 mutation carrier increased with number of selected histology features even after adjusting for family history and ER and PR status (Po0.0001). From the most parsimonious multivariate model, the odds ratio for being a carrier were: 9.7 (95% confidence interval: 2.6-47.0) for trabecular growth pattern (P=0.001); 7.8 (2.7-25.7) for mitotic index over 50 mitoses per 10 high-powered field (P 0.0003); and 2.7 (1.3-5.9) for each first-degree relative with breast cancer diagnosed before age 60 years (P 0.01). The area under the ROC curve was 0.87 (0.83-0.90).CONCLUSION: Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost all BRCA1 germline mutation carriers among women with early-onset breast cancer without taking into account family history. British Journal of Cancer (2011) 104, 903-909. doi: 10.1038/ bjc. 2011.41 www. bjcancer. co

Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates