Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia ...(HTG) and a markedly increased risk of acute pancreatitis. It is due to the lack of lipoprotein lipase (LPL) function, resulting from recessive loss of function mutations in the genes coding LPL or its modulators. A large overlap in the phenotype between FCS and multifactorial chylomicronaemia syndrome (MCS) contributes to the inconsistency in how patients are diagnosed and managed worldwide, whereas the incidence of acute hypertriglyceridaemic pancreatitis is more frequent in FCS. A panel of European experts provided guidance on the diagnostic strategy surrounding FCS and proposed an algorithm-based diagnosis tool for identification of these patients, which can be readily translated into practice. Features included in this FCS score comprise: severe elevation of plasma TGs (fasting TG levels >10 mmol/L 885 mg/dL on multiple occasions), refractory to standard TG-lowering therapies, a young age at onset, the lack of secondary factors (except for pregnancy and oral oestrogens) and a history of episodes of acute pancreatitis. Considering 53 FCS patients from three cohorts and 52 MCS patients from three cohorts, the overall sensitivity of the FCS score (≥10) was 88% (95% confidence interval CI: 0.76, 0.97) with an overall specificity of 85% (95% CI: 0.75, 0.94). Receiver operating characteristic curve area was 0.91. Pragmatic clinical scoring, by standardising diagnosis, may help differentiate FCS from MCS, may alleviate the need for systematic genotyping in patients with severe HTG and may help identify high-priority candidates for genotyping.
•The boundaries between familial chylomicronaemia syndrome (FCS) and multifactorial chylomicronaemia syndrome are defined.•A clinical diagnostic scoring system is proposed to aid diagnosis of FCS.•Validation of the algorithm has been performed using existing genotyped cohorts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
ABSTRACT We report for the first time a γ-ray and multiwavelength nearly periodic oscillation in an active galactic nucleus. Using the Fermi Large Area Telescope we have discovered an apparent ...quasi-periodicity in the γ-ray flux (E > 100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The marginal significance of the 2.18 0.08 year period γ-ray cycle is strengthened by correlated oscillations observed in radio and optical fluxes, through data collected in the Owens Valley Radio Observatory, Tuorla, Katzman Automatic Imaging Telescope, and Catalina Sky Survey monitoring programs and Swift-UVOT. The optical cycle appearing in ∼10 years of data has a similar period, while the 15 GHz oscillation is less regular than seen in the other bands. Further long-term multiwavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.
We conducted population-based surveys on direct-to-consumer nutrigenomic testing in Michigan, Oregon, and Utah as part of the 2006 Behavioral Risk Factor Surveillance System. Awareness of the tests ...was highest in Oregon (24.4%) and lowest in Michigan (7.6%). Predictors of awareness were more education, higher income, and increasing age, except among those 65 years or older. Less than 1% had used a health-related direct-to-consumer genetic test. Public health systems should increase consumer and provider education and continue surveillance on direct-to-consumer genetic tests.
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CEKLJ, DOBA, FSPLJ, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background: Because of high single-agent activity and modest toxicity, we hypothesized the combination of gemcitabine (G), vinorelbine (V), and pegylated liposomal doxorubicin (D) would be an ...effective salvage therapy for Hodgkin's lymphoma (HL). Patients and methods: A total of 91 patients participated. GVD was administered on days 1 and 8 every 21 days at doses of G 1000 mg/m2, V 20 mg/m2, and D 15 mg/m2 for transplant-naive patients, and G 800 mg/m2, V 15 mg/m2, and D 10 mg/m2 for post-transplant patients. Results: The dose-limiting toxicity was mucositis for the transplant-naive patients and febrile neutropenia for post-transplant patients. The overall response rate (RR) for all patients was 70% 95% confidence interval (CI) 59.8, 79.7, with 19% complete remissions. The 4-year event-free and overall survival rates in transplant-naive patients treated with GVD followed by autologous transplant were 52% (95% CI 0.34, 0.68) and 70% (95% CI 0.49, 0.84), and in the patients in whom prior transplant failed, these were 10% (95% CI 0.03, 0.22) and 34% (95% CI 0.17, 0.52), respectively. Conclusions: GVD is a well-tolerated, active regimen for relapsed HL with results similar to those reported for more toxic regimens. High RRs in patients in whom prior transplant failed confirms this regimen's activity even in heavily pretreated patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease ...activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH 2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+ , CD11c+ , and FcεRI+ ) than adults with AD. Similar to adults, strong activation of the TH 2 (IL-13, IL-31, and CCL17) and TH 22 (IL-22 and S100As) axes and some TH 1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH 17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH 9/IL-9, IL-33, and innate markers (IL-8) than adults ( P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers ( P < .001). Conclusion The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH 2 activation characterizes both, TH 9 and TH 17 are highly activated at disease initiation. Increases in IL-19 levels might link TH 2 and TH 17 activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cannabinoid Receptor Localization in Brain Herkenham, Miles; Lynn, Allison B.; Little, Mark D. ...
Proceedings of the National Academy of Sciences - PNAS,
03/1990, Volume:
87, Issue:
5
Journal Article
Peer reviewed
Open access
3HCP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than Δ9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in ...brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of 3HCP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia-the substantia nigra pars reticulata and globus pallidus-and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of Δ9-tetrahydrocannabinol are not lethal.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We measured the δ18O of cellulose (δ18Ocel) extracted from fossil wood collected at 9 sites in the northern and southern hemispheres as a potential source of information about precipitation δ18O ...(δ18Oppt) in the past and paleotemperatures. The samples had been buried in fluvial sediments for periods of time ranging from ca. 45 million to 250 years. At the oldest localities (high latitude, Eocene- through Pliocene-age sites in Canada and Russia), mean annual temperature (MAT) estimates derived from the modern relationship between MAT and δ18Ocel are 6–16°C lower than the MAT estimates derived from other biological proxies. Estimates of Pleistocene and Holocene mean annual temperatures are close to the modern values at those sites. These results are consistent with other recent findings that the MAT/δ18Oppt relationship across North America was not constant throughout the Cenozoic. Paleo-δ18Oppt estimates derived from fossil cellulose and the modern North American relationship between δ18Ocel and δ18Oppt are within the current annual range of δ18Oppt values at all locations. The middle Eocene δ18Oppt we determined from arctic cellulose samples (−21.9‰) is consistent with river water δ18O determined in two other studies (−19.1‰ to −22‰). These findings provide some evidence that a precipitation δ18O signal may be retained in wood cellulose during millions of years of burial, and that latitudinal patterns in δ18Oppt may not have changed much during the past 45Ma. These interpretations depend, of course, on the assumption that the isotopic composition of the cellulose has not changed during burial, an assumption for which it is difficult to gather direct evidence. XRD analysis shows that the crystalline form of the fossil cellulose we used to estimate paleoprecipitation δ18O and paleo-MAT is the same as that of modern cellulose, and that the samples are free of quartz and iron oxide contaminants that result in negative errors in measured δ18Ocel.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
499.
Solar fusion cross sections Adelberger, Eric G.; Austin, Sam M.; Bahcall, John N. ...
Reviews of modern physics,
10/1998, Volume:
70, Issue:
4
Journal Article
Peer reviewed
Open access
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Numerous loose rocks with dimensions of a few centimeters to tens of centimeters and with no obvious physical relationship to outcrop rocks have been observed along the traverse of the Mars ...Exploration Rover Opportunity. To date, about a dozen of these rocks have been analyzed with Opportunity's contact instruments, providing information about elemental chemistry (Alpha Particle X‐ray Spectrometer), iron mineralogy and oxidation states (Mössbauer Spectrometer) and texture (Microscopic Imager). These “cobbles” appear to be impact related, and three distinct groups can be identified on the basis of chemistry and mineralogy. The first group comprises bright fragments of the sulfate‐rich bedrock that are compositionally and texturally indistinguishable from outcrop rocks. All other cobbles are dark and are divided into two groups, referred to as the “Barberton group” and the “Arkansas group,” after the first specimen of each that was encountered by Opportunity. Barberton group cobbles are interpreted as meteorites with an overall chemistry and mineralogy consistent with a mesosiderite silicate clast composition. Arkansas group cobbles appear to be related to Meridiani outcrop and contain an additional basaltic component. They have brecciated textures, pointing to an impact‐related origin during which local bedrock and basaltic material were mixed.
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