1,425 research outputs found

    Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice

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    Neuroinflammation and neurodegeneration have been observed in the brain in type 1 diabetes (T1D). However, little is known about the mediators of these effects. In T1D mice with 12- and 35-wk duration of diabetes we examined two mechanisms of neurodegeneration, loss of the neuroprotective factors insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and changes in indoleamine 2,3-dioxygenase (IDO) expression in the brain, and compared the response to age-matched controls. Furthermore, levels of matrix metalloproteinase-2 (MMP-2), nucleoside triphosphate diphosphohydrolase-1 (CD39), and ionized calcium-binding adaptor molecule 1 (Iba-1) were utilized to assess inflammatory changes in astrocytes, microglia, and blood vessels. In the diabetic hypothalamus (HYPO), we observed 20% reduction in neuronal soma diameter (P<0.05) and reduced neuronal expression of IGFBP-3 (-32%, P<0.05) and IGF-I (-15%, P<0.05) compared with controls at 35 wk. In diabetic HYPO, MMP-2 expression was increased in astrocytes (46%, P<0.01), and IDO⁺ cell density rose by (62%, P<0.05). CD39 expression dropped by 30% (P<0.05) in microglia and blood vessels. With 10 wk of systemic treatment using minocycline, an anti-inflammatory agent that crosses the blood-brain barrier, MMP-2, IDO, and CD39 levels normalized (P<0.05). Our results suggest that increased IDO and early loss of CD39⁺ protective cells lead to activation of inflammation in sympathetic centers of the CNS. As a downstream effect, the loss of the neuronal survival factors IGFBP-3 and IGF-I and the neurotoxic products of the kynurenine pathway contribute to the loss of neuronal density observed in the HYPO in T1D

    N-String Vertices in String Field Theory

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    We give the general form of the vertex corresponding to the interaction of an arbitrary number of strings. The technique employed relies on the ``comma" representation of String Field Theory where string fields and interactions are represented as matrices and operations between them such as multiplication and trace. The general formulation presented here shows that the interaction vertex of N strings, for any arbitrary N, is given as a function of particular combinations of matrices corresponding to the change of representation between the full string and the half string degrees of freedom.Comment: 22 pages, A4-Latex (latex twice), FTUV IFI

    Star formation histories of dwarf galaxies in the FIRE simulations: dependence on mass and Local Group environment

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    We study star formation histories (SFHs) of 500\simeq500 dwarf galaxies (stellar mass M=105109MM_\ast = 10^5 - 10^9\,M_\odot) from FIRE-2 cosmological zoom-in simulations. We compare dwarfs around individual Milky Way (MW)-mass galaxies, dwarfs in Local Group (LG)-like environments, and true field (i.e. isolated) dwarf galaxies. We reproduce observed trends wherein higher-mass dwarfs quench later (if at all), regardless of environment. We also identify differences between the environments, both in terms of "satellite vs. central" and "LG vs. individual MWvs. isolated dwarf central." Around the individual MW-mass hosts, we recover the result expected from environmental quenching: central galaxies in the "near field" have more extended SFHs than their satellite counterparts, with the former more closely resemble isolated ("true field") dwarfs (though near-field centrals are still somewhat earlier forming). However, this difference is muted in the LG-like environments, where both near-field centrals and satellites have similar SFHs, which resemble satellites of single MW-mass hosts. This distinction is strongest for M=106107MM_\ast = 10^6 - 10^7\,M_\odot but exists at other masses. Our results suggest that the paired halo nature of the LG may regulate star formation in dwarf galaxies even beyond the virial radii of the MW and Andromeda. Caution is needed when comparing zoom-in simulations targeting isolated dwarf galaxies against observed dwarf galaxies in the LG.Comment: Main text: 11 pages, 8 figures; appendices: 4 pages, 4 figures. Submitted to MNRAS; comments welcom

    Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

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    INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy

    A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases.

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    We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure

    A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing.

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    Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC

    Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys

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    Objective To assess the acceptability of pre-pandemic influenza vaccination among healthcare workers in public hospitals in Hong Kong and the effect of escalation in the World Health Organization’s alert level for an influenza pandemic

    Ad hoc influenza vaccination during years of significant antigenic drift in a tropical city with 2 seasonal peaks

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    We evaluated the acceptability of an additional ad hoc influenza vaccination among the health care professionals following seasons with significant antigenic drift. Self-administered, anonymous surveys were performed by hard copy questionnaires in public hospitals, and by an on-line platform available to all healthcare professionals, from April 1st to May 31st, 2015. A total of 1290 healthcare professionals completed the questionnaires, including doctors, nurses, and allied health professionals working in both the public and private systems. Only 31.8% of participating respondents expressed an intention to receive the additional vaccine, despite that the majority of them agreed or strongly agreed that it would bring benefit to the community (88.9%), save lives (86.7%), reduce medical expenses (76.3%), satisfy public expectation (82.8%), and increase awareness of vaccination (86.1%). However, a significant proportion expressed concern that the vaccine could disturb the normal immunization schedule (45.5%); felt uncertain what to do in the next vaccination round (66.0%); perceived that the summer peak might not occur (48.2%); and believed that the summer peak might not be of the same virus (83.5%). Furthermore, 27.8% of all respondents expected that the additional vaccination could weaken the efficacy of previous vaccinations; 51.3% was concerned about side effects; and 61.3% estimated that there would be a low uptake rate. If the supply of vaccine was limited, higher priority groups were considered to include the elderly aged ≥65 years with chronic medical conditions (89.2%), the elderly living in residential care homes (87.4%), and long-stay residents of institutions for the disabled (80.7%). The strongest factors associated with accepting the additional vaccine included immunization with influenza vaccines in the past 3 years, higher perceived risk of contracting influenza, and higher perceived severity of the disease impact. The acceptability to an additional ad hoc influenza vaccination was low among healthcare professionals. This could have a negative impact on such additional vaccination campaigns since healthcare professionals are a key driver for vaccine acceptance. The discordance in perceived risk and acceptance of vaccination regarding self versus public deserves further evaluation

    Far-ultraviolet Spectroscopy of Venus and Mars at 4 A Resolution with the Hopkins Ultraviolet Telescope on Astro-2

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    Far-ultraviolet spectra of Venus and Mars in the range 820-1840 A at 4 A resolution were obtained on 13 and 12 March 1995, respectively, by the Hopkins Ultraviolet Telescope (HUT), which was part of the Astro-2 observatory on the Space Shuttle Endeavour. Longward of 1250 A, the spectra of both planets are dominated by emission of the CO Fourth Positive band system and strong OI and CI multiplets. In addition, CO Hopfield-Birge bands, B - X (0,0) at 1151 A and C - X (0,0) at 1088 A, are detected for the first time, and there is a weak indication of the E - X (0,0) band at 1076 A in the spectrum of Venus. The B - X band is blended with emission from OI 1152. Modeling the relative intensities of these bands suggests that resonance fluorescence of CO is the dominant source of the emission, as it is for the Fourth Positive system. Shortward of Lyman-alpha, other emission features detected include OII 834, OI lambda 989, HI Lyman-beta, and NI 1134 and 1200. For Venus, the derived disk brightnesses of the OI, OII, and HI features are about one-half of those reported by Hord et al. (1991) from Galileo EUV measurements made in February 1990. This result is consistent with the expected variation from solar maximum to solar minimum. The ArI 1048, 1066 doublet is detected only in the spectrum of Mars and the derived mixing ratio of Ar is of the order of 2%, consistent with previous determinations.Comment: 8 pages, 5 figures, accepted for publication in ApJ, July 20, 200
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