2,249 research outputs found
Primary CNS lymphoma with intravitreal metastasis : using vitreous cavity samples to monitor response to therapy
A fifty-eight year old male patient presented to the
ophthalmic department with a 3 day history of reduced
visual acuity, blurred vision and floaters, associated with
recent lethargy, headaches and behavioural changes.
Fundal examination revealed a bilateral vitritis. Steroid
therapy was started. MRI of the brain revealed multiple
hypodense and hyperdense lesions. Vitrectomy was
performed in view of the poor response to steroids. A
biopsy showed non-hodgkin B-Cell lymphoma. The
patient was started on intravenous Methotrexate and
Cytarabine. Repeat vitreous cavity biopsies were
performed in order to assess response to therapy. All
biopsies to date have revealed evidence of on-going
lymphoma.peer-reviewe
Sudden bilateral loss of vision in a 19-year-old man
Introduction: Posterior Reversible
Leukoencephalopathy Syndrome (PRES) is caused by
ischaemia commonly affecting the posterior cerebral
vasculature. It presents with sudden decreased vision,
headaches, nausea, vomiting, seizures, and altered
mental status.
Case presentation: A 19-year-old male presented to
the ophthalmic emergency complaining of sudden
bilateral loss of vision, which was down to light
perception He reported headaches, nausea, and
drowsiness since the previous day. He was a known case
of hypertension secondary to IgA nephropathy.
Magnetic resonance imaging (MRI) with STIR and
FLAIR sequences showed foci of hyperintensity within
the occipital lobes bilaterally. This confirmed the
suspected diagnosis of PRES. Discussion: Aetiological factors of PRES include
sudden increase in blood pressure, eclampsia, porphyria,
renal disease, and Cushing syndrome. These lead to
blood-brain barrier injury either by hyper- or hypoperfusion,
endothelial dysfunction, changes in blood
vessel morphology, hypocapnea, or immune system
activation. Histopathological changes in PRES include
activated astrocytes, scattered macrophages and
lymphocytes, often in the absence of inflammation or
neuronal damage.
Conclusion: PRES is usually a reversible neuroophthalmological
condition, however prompt
recognition and appropriate management is important to
prevent permanent brain injury or even death.peer-reviewe
Inclusive School Community: Why is it so Complex?
This paper addresses the question: why is it so hard for school communities to respond to diversity in learners, staff and parents in inclusive ways? The authors draw on theory and recent professional experience in Queensland, Australia, to offer four guiding principles that address traditional assumptions about learning that result in inequality of opportunity and outcomes for students. The authors suggest these principles to support the development of a more inclusive school community: (1) develop a learning community incorporating a critical friend; (2) value and collaborate with parents and the broader community; (3) engage students as citizens in school review and develop¬ment; and (4) support teachers’ critical engagement with inclusive ideals and practices. The authors describe how the principles can work in concert in a school community
The K2 Mission: Characterization and Early results
The K2 mission will make use of the Kepler spacecraft and its assets to
expand upon Kepler's groundbreaking discoveries in the fields of exoplanets and
astrophysics through new and exciting observations. K2 will use an innovative
way of operating the spacecraft to observe target fields along the ecliptic for
the next 2-3 years. Early science commissioning observations have shown an
estimated photometric precision near 400 ppm in a single 30 minute observation,
and a 6-hour photometric precision of 80 ppm (both at V=12). The K2 mission
offers long-term, simultaneous optical observation of thousands of objects at a
precision far better than is achievable from ground-based telescopes. Ecliptic
fields will be observed for approximately 75-days enabling a unique exoplanet
survey which fills the gaps in duration and sensitivity between the Kepler and
TESS missions, and offers pre-launch exoplanet target identification for JWST
transit spectroscopy. Astrophysics observations with K2 will include studies of
young open clusters, bright stars, galaxies, supernovae, and asteroseismology.Comment: 25 pages, 11 figures, Accepted to PAS
A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes
Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression
Chloroquine is a potent inhibitor of SARS coronavirus infection and spread
BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available. RESULTS: We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations. CONCLUSION: Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds
Different Fumaric Acid Esters Elicit Distinct Pharmacologic Responses.
OBJECTIVE
To test the hypothesis that dimethyl fumarate (DMF, Tecfidera) elicits different biological changes from DMF combined with monoethyl fumarate (MEF) (Fumaderm, a psoriasis therapy), we investigated DMF and MEF in rodents and cynomolgus monkeys. Possible translatability of findings was explored with lymphocyte counts from a retrospective cohort of patients with MS.
METHODS
In rodents, we evaluated pharmacokinetic and pharmacodynamic effects induced by DMF and MEF monotherapies or in combination (DMF/MEF). Clinical implications were investigated in a retrospective, observational analysis of patients with MS treated with DMF/MEF (n = 36).
RESULTS
In rodents and cynomolgus monkeys, monomethyl fumarate (MMF, the primary metabolite of DMF) exhibited higher brain penetration, whereas MEF was preferentially partitioned into the kidney. In mice, transcriptional profiling for DMF and MEF alone identified both common and distinct pharmacodynamic responses, with almost no overlap between DMF- and MEF-induced differentially expressed gene profiles in immune tissues. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated oxidative stress response pathway was exclusively regulated by DMF, whereas apoptosis pathways were activated by MEF. DMF/MEF treatment demonstrated that DMF and MEF functionally interact to modify DMF- and MEF-specific responses in unpredictable ways. In patients with MS, DMF/MEF treatment led to early and pronounced suppression of lymphocytes, predominantly CD8+ T cells. In a multivariate regression analysis, the absolute lymphocyte count (ALC) was associated with age at therapy start, baseline ALC, and DMF/MEF dosage but not with previous immunosuppressive medication and sex. Furthermore, the ALC increased in a small cohort of patients with MS (n = 6/7) after switching from DMF/MEF to DMF monotherapy.
CONCLUSIONS
Fumaric acid esters exhibit different biodistribution and may elicit different biological responses; furthermore, pharmacodynamic effects of combinations differ unpredictably from monotherapy. The strong potential to induce lymphopenia in patients with MS may be a result of activation of apoptosis pathways by MEF compared with DMF
The Atacama Cosmology Telescope: The LABOCA/ACT Survey of Clusters at All Redshifts
We present a multi-wavelength analysis of eleven Sunyaev Zel'dovich effect
(SZE)-selected galaxy clusters (ten with new data) from the Atacama Cosmology
Telescope (ACT) southern survey. We have obtained new imaging from the Large
APEX Bolometer Camera (345GHz; LABOCA) on the Atacama Pathfinder EXperiment
(APEX) telescope, the Australia Telescope Compact Array (2.1GHz; ATCA), and the
Spectral and Photometric Imaging Receiver (250, 350, and ;
SPIRE) on the Herschel Space Observatory. Spatially-resolved 345GHz SZE
increments with integrated S/N > 5 are found in six clusters. We compute 2.1GHz
number counts as a function of cluster-centric radius and find significant
enhancements in the counts of bright sources at projected radii . By extrapolating in frequency, we predict that the combined
signals from 2.1GHz-selected radio sources and 345GHz-selected SMGs contaminate
the 148GHz SZE decrement signal by ~5% and the 345GHz SZE increment by ~18%.
After removing radio source and SMG emission from the SZE signals, we use ACT,
LABOCA, and (in some cases) new Herschel SPIRE imaging to place constraints on
the clusters' peculiar velocities. The sample's average peculiar velocity
relative to the cosmic microwave background is .Comment: 19 pages, 11 figures, Accepted for Publication in The Astrophysical
Journa
Evaluation of SMN Protein, Transcript, and Copy Number in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study
BACKGROUND: The universal presence of a gene (SMN2) nearly identical to the mutated SMN1 gene responsible for Spinal Muscular Atrophy (SMA) has proved an enticing incentive to therapeutics development. Early disappointments from putative SMN-enhancing agent clinical trials have increased interest in improving the assessment of SMN expression in blood as an early "biomarker" of treatment effect. METHODS: A cross-sectional, single visit, multi-center design assessed SMN transcript and protein in 108 SMA and 22 age and gender-matched healthy control subjects, while motor function was assessed by the Modified Hammersmith Functional Motor Scale (MHFMS). Enrollment selectively targeted a broad range of SMA subjects that would permit maximum power to distinguish the relative influence of SMN2 copy number, SMA type, present motor function, and age. RESULTS: SMN2 copy number and levels of full-length SMN2 transcripts correlated with SMA type, and like SMN protein levels, were lower in SMA subjects compared to controls. No measure of SMN expression correlated strongly with MHFMS. A key finding is that SMN2 copy number, levels of transcript and protein showed no correlation with each other. CONCLUSION: This is a prospective study that uses the most advanced techniques of SMN transcript and protein measurement in a large selectively-recruited cohort of individuals with SMA. There is a relationship between measures of SMN expression in blood and SMA type, but not a strong correlation to motor function as measured by the MHFMS. Low SMN transcript and protein levels in the SMA subjects relative to controls suggest that these measures of SMN in accessible tissues may be amenable to an "early look" for target engagement in clinical trials of putative SMN-enhancing agents. Full length SMN transcript abundance may provide insight into the molecular mechanism of phenotypic variation as a function of SMN2 copy number. TRIAL REGISTRY: Clinicaltrials.gov NCT00756821
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