Duodenal Villous Atrophy in a TTG-Negative Patient Taking Olmesartan: A Case Report and Review of the Literature

Olmesartan, an angiotensin II receptor antagonist used to treat hypertension, is associated with few adverse effects. Here, a case of severe sprue-like enteropathy and acute kidney injury is described in a 68-year-old male taking olmesartan for 3-4 years. He presented to hospital with a five-week history of diarrhea, vomiting, and a 20 lb weight loss. Anti-TTG was negative with a normal IgA. Biopsies of the distal duodenum and duodenal cap revealed marked blunting of the villi with near complete villous atrophy of the biopsies from the bulb. There was an increase in intraepithelial lymphocytes as well as neutrophils in the surface epithelium. The patient’s diarrhea improved upon discontinuation of olmesartan and he returned to his previous weight. Repeat endoscopy four months later demonstrated complete resolution of inflammatory change with normal villous architecture. Long-term olmesartan use is associated with severe sprue-like enteropathy. The mechanism of intestinal injury is unknown. Duodenal biopsy results may mimic other enteropathies such as celiac disease. Physicians should consider medications as potential etiologies of enteropathy

Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species

Preliminary study: Treatment with intramuscular interferon beta-1a results in increased levels of IL-12Rβ2+ and decreased levels of IL23R+ CD4+ T - Lymphocytes in multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>There are a lack of biomarkers which can be used to predict clinical outcomes for multiple sclerosis (MS) patients receiving interferon beta (IFN-β). Thus the objective of this study was to characterize changes in CD4+ T-lymphocyte expression in an unbiased manner following initiation of intramuscular (IM) IFN-β-1a treatment, and then to verify those findings using marker-specific assays.</p> <p>Methods</p> <p>Peripheral blood specimens were collected from twenty MS patients before and after treatment with intramuscular (IM) IFN-β-1a and were used for isolation of mononuclear cells (PBMCs). mRNA expression patterns of negatively-selected CD4+ T-cells from the PBMCs were analyzed using microarray gene expression technology. IL-12 and IL-23 receptor levels on PBMC-derived CD4+ T-cells were analyzed by flow cytometry. The phosphorylation status of Stat4 was measured by performing densitometry on western blots.</p> <p>Results</p> <p>Microarray analyses demonstrated that mRNA expression of the IL-12Rβ2 gene was uniformly up-regulated in response to IFN-β-1a treatment and was associated with an increased number of IL-12Rβ2⁺CD4⁺T-cells by flow cytometry in 4 of 6 patients. This finding was substantiated by demonstrating that Stat4 phosphorylation, a transcription factor for IL-12, was increased after treatment. Conversely, the number of IL-23R⁺CD4⁺T-cells was decreased following treatment.</p> <p>Conclusions</p> <p>The IL-12 receptor shares a common subunit, the IL-12Rβ2, with the IL-23 receptor. Both of these receptors have a probable role in regulating IL-17 and TH-17 cells, important mediators of inflammation in multiple sclerosis (MS). Thus, the changes in the numbers of CD4⁺T-cells expressing these receptors in response to IFN-β-1a treatment may point to an important mechanism of action for this drug, but further large scale studies are needed to confirm these preliminary observations.</p

Forecasts, scenarios, visions, backcasts and roadmaps to the hydrogen economy: a review of the hydrogen futures literature

Scenarios, roadmaps and similar foresight methods are used to cope with uncertainty in areas with long planning horizons, such as energy policy, and research into the future of hydrogen energy has been no exception. Such studies can play an important role in the development of shared visions of the future: creating powerful expectations of the potential of emerging technologies and mobilising resources necessary for their realisation. This paper reviews the hydrogen futures literature, using a six-fold typology to map the state of the art of scenario construction. The paper then explores the expectations embodied in the literature, through the 'answers' it provides to questions about the future of hydrogen. What are the drivers, barriers and challenges facing the development of a hydrogen economy? What are the key technological building blocks required? In what kinds of futures does hydrogen become important? What does a hydrogen economy look like, how and when does it evolve, and what does it achieve? The literature describes a diverse range of possible futures, from decentralised systems based upon the small-scale renewables, through to centralised systems reliant on nuclear energy or carbon-sequestration. There is a broad consensus that the hydrogen economy emerges only slowly, if all under 'Business as Usual' scenarios. Rapid transitions to hydrogen occur only under conditions of strong governmental support combined with, or as a result of, major 'discontinuities' such as shifts in society's environmental values, 'game changing' technological breakthroughs, or rapid increases in the oil price or speed and intensity of climate change

Running Speed in Mammals Increases with Muscle n-6 Polyunsaturated Fatty Acid Content

Polyunsaturated fatty acids (PUFAs) are important dietary components that mammals cannot synthesize de novo. Beneficial effects of PUFAs, in particular of the n-3 class, for certain aspects of animal and human health (e.g., cardiovascular function) are well known. Several observations suggest, however, that PUFAs may also affect the performance of skeletal muscles in vertebrates. For instance, it has been shown that experimentally n-6 PUFA-enriched diets increase the maximum swimming speed in salmon. Also, we recently found that the proportion of PUFAs in the muscle phospholipids of an extremely fast runner, the brown hare (Lepus europaeus), are very high compared to other mammals. Therefore, we predicted that locomotor performance, namely running speed, should be associated with differences in muscle fatty acid profiles. To test this hypothesis, we determined phospholipid fatty acid profiles in skeletal muscles of 36 mammalian species ranging from shrews to elephants. We found that there is indeed a general positive, surprisingly strong relation between the n-6 PUFAs content in muscle phospholipids and maximum running speed of mammals. This finding suggests that muscle fatty acid composition directly affects a highly fitness-relevant trait, which may be decisive for the ability of animals to escape from predators or catch prey

Radiation of Extant Cetaceans Driven by Restructuring of the Oceans

The remarkable fossil record of whales and dolphins (Cetacea) has made them an exemplar of macroevolution. Although their overall adaptive transition from terrestrial to fully aquatic organisms is well known, this is not true for the radiation of modern whales. Here, we explore the diversification of extant cetaceans by constructing a robust molecular phylogeny that includes 87 of 89 extant species. The phylogeny and divergence times are derived from nuclear and mitochondrial markers, calibrated with fossils. We find that the toothed whales are monophyletic, suggesting that echolocation evolved only once early in that lineage some 36–34 Ma. The rorqual family (Balaenopteridae) is restored with the exclusion of the gray whale, suggesting that gulp feeding evolved 18–16 Ma. Delphinida, comprising all living dolphins and porpoises other than the Ganges/Indus dolphins, originated about 26 Ma; it contains the taxonomically rich delphinids, which began diversifying less than 11 Ma. We tested 2 hypothesized drivers of the extant cetacean radiation by assessing the tempo of lineage accumulation through time. We find no support for a rapid burst of speciation early in the history of extant whales, contrasting with expectations of an adaptive radiation model. However, we do find support for increased diversification rates during periods of pronounced physical restructuring of the oceans. The results imply that paleogeographic and paleoceanographic changes, such as closure of major seaways, have influenced the dynamics of radiation in extant cetaceans

Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

BackgroundFor patients with high grade serous carcinoma of the ovary (HGSC), survival rates have remained static for the last half century. Despite the presence of tumor mutations and infiltration of immune cells, existing immunotherapies have achieved little success against HGSC. These observations highlight a gap in the understanding of how the immune system functions and interacts within HGSC tumors.MethodsWe analyzed duplicate core samples from 939 patients with HGSC to understand patterns of immune cell infiltration, localization, and associations with clinical features. We used high-parameter immunohistochemical/Opal multiplex, digital pathology, computational biology, and multivariate analysis to identify immune cell subsets and their associations with HGSC tumors.ResultsWe defined six patterns of cellular infiltration by spatially restricted unsupervised clustering of cell subsets. Each pattern was represented to some extent in most patient samples, but their specific distributions differed. Overall (OS) and progression-free survival (PFS) corresponded with higher infiltration of CD16a+ cells, and their co-localization with macrophages, T cells, NK cells, in one of six cellular neighborhoods that we defined with our spatial assessment.ConclusionsImmune cell neighborhoods containing CD16a+ cells are associated with improved OS and PFS for patients with HGSC. Patterns of immunologic neighborhoods differentiate patient outcomes, and could inform future, more precise approaches to treatment

Fuel reduction in coastal squid jigging boats equipped with various combinations of conventional metal halide lamps and low-energy LED panels

Application of the low-energy light emitting diode (LED) is considered as a possible measure for fuel saving in the squid jigging fishery. We monitored fuel consumption of 14 coastal squid jigging boats ranging in size from 6.6 to 19. gross tons (GT) operating in the northern and western waters of the Sea of Japan in 2009-2011. In summer in the northern waters, squid boats of 19. GT consumed approximately 900. l in one operation that lasted from the afternoon to the next morning and 54% of the fuel was used during jigging with 53 conventional metal halide lamps (MHs) of 159. kW in total. In winter in the western waters, the total amount of fuel consumed in conventional operations of the 6.6-16. GT boats was less, but fuel consumption during jigging with lamps accounted for 70-78% of the total consumption due to close fishing grounds. The relationship between fuel consumption (l) and energy (kW. h) during jigging with lamps was expressed as a linear regression containing effects of the boat size and the inherent character of each boat. Fuel consumption rate decreases on average 0.28. l/kW. h by using LEDs with a reduced number of MHs. When 9. kW LEDs were employed with 24. MHs for 19. GT boat in the western water in summer, 24% fuel saving was estimated

Acquired inflammatory demyelinating polyneuropathies: Clinical and electrodiagnostic features

The acquired demyelinating polyneuropathies include acute (AIDP, Guillain-BarrÉ syndrome, GBS) and chronic (CIDP, dysproteinemic) forms which differ primarily in their temporal profile. They are inflammatory-demyelinating diseases of the peripheral nervous system and likely have an immunologic pathogenesis. Although these neuropathies usually have a characteristic presentation, the electromyographer plays a central role in their recognition, since the demyelinating component of the neuropathy, which greatly reduces the differential diagnosis, is often first identified in the electromyography laboratory. In AIDP, the electromyographer, in addition to establishing the diagnosis, can sometimes predict the prognosis. Recognition of the chronic and dysproteinemic forms of acquired demyelinating polyneuropathy is important since they are treatable. The dysproteinemic forms also may be associated with occult systemic disorders that also may require treatment, independent of the neuropathy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50143/1/880120602_ftp.pd

Neuropathological Findings In Chronic Relapsing Experimental Allergic Neuritis Induced In The Lewis Rat By Inoculation With Intradural Root Myelin And Treatment With Low Dose Cyclosporin A

Experimental allergic neuritis (EAN) was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. Rats treated with subcutaneous cyclosporin A (CsA) (4mg/kg on 3 days per week from the day of inoculation until day 29) developed a chronic relapsing course. Tissues from the spinal cord, nerve roots, dorsal root ganglia and sciatic nerve of CsA-treated rats sampled during relapses and remissions were studied during or after episodes of acute EAN. Both control and CsA-treated animals studied in the first episode of EAN had evidence of inflammation and primary demyelination of the nerve roots and dorsal root ganglia. In control and CsA-treated animals in the second episode there was severe inflammation and demyelination and remyelination in the spinal nerves and sciatic nerves and dorsal columns of the spinal cord, particularly in later stages of the disease. In later episodes there was less inflammation, but there was continuing demyelination and onion bulbs were present. In animals sampled after recovery from chronic relapsing EAN onion bulbs were present. Occasional small onion bulbs were also observed in control animals that were inoculated with higher doses of myelin. Plasma cells were present in the inflammatory lesions of later episodes. Mast cells were also observed at different stages of the disease. We conclude that the CsA form of chronic relapsing EAN has clinical and pathological similarities with the human disease, chronic inflammatory demyelinating polyradiculoneuropathy