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1.
J Neurol ; 269(12): 6582-6588, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35997818

ABSTRACT

BACKGROUND: Established features of classical infratentorial superficial siderosis (iSS) include hearing loss, impaired balance, myelopathy and, less commonly, cognitive compromise. Olfactory function may be affected but dedicated studies are lacking. This study aimed to assess the prevalence of olfactory dysfunction in iSS and correlate it with auditory and cognitive functions. METHODS: Ten participants with iSS completed the University of Pennsylvania Smell Identification Test (UPSIT). The scores were compared with population norms; regression analysis was performed to evaluate associations between the scores and hearing thresholds (3-frequency average, 3FA) or the number of cognitive domains impaired. Imaging was reviewed for haemosiderin distribution and to exclude other causes of olfactory and hearing dysfunction. RESULTS: Eight of ten participants were male; the mean (standard deviation, SD) age was 52.5 (14.5) years. Olfactory hypofunction was identified in all participants and in six (60%) was moderate or completely absent. The mean UPSIT score of 25.5 (7.8) was significantly worse than population norms (difference in means - 10.0; 95% CI - 15.6 to - 4.4). Linear regression identified an association between UPSIT and hearing thresholds (R = 0.75; p = 0.013). The score decreases by 0.157 units (95% CI - 0.31 to - 0.002; p = 0.048) per unit increase in 3FA, after adjusting for hearing loss risk factors. There was no statistically significant association between UPSIT and cognitive function (R = 0.383; p = 0.397). CONCLUSION: We report a high prevalence of olfactory dysfunction in iSS, the severity of which correlated with hearing loss. Olfaction appears to be a core feature of the iSS clinical syndrome that should be assessed routinely.


Subject(s)
Olfaction Disorders , Siderosis , Male , Humans , Middle Aged , Female , Smell , Olfaction Disorders/diagnostic imaging , Olfaction Disorders/epidemiology , Olfaction Disorders/etiology , Siderosis/complications , Siderosis/diagnostic imaging , Siderosis/epidemiology , Cognition , Central Nervous System
2.
Clin Radiol ; 76(6): 470.e1-470.e12, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33610289

ABSTRACT

Patients with haematological malignancy are at increased risk of developing central nervous system (CNS) infections, which are associated with significant morbidity and mortality. Neuroimaging plays a pivotal role in the diagnostic pathway of these patients; however, layers of complexity are added to image interpretation by the heterogeneity in imaging manifestations of haematological malignancies in the CNS, overlapping imaging features of CNS infection, treatment-related parenchymal changes and the presence of intracranial comorbidity. In this article, we review important intracranial findings of CNS infection cases accrued in 1,855 studies over more than a decade at a specialist tertiary centre. We offer schema to identify common and important neuroimaging features, discuss key differential diagnoses and frequent diagnostic pitfalls.


Subject(s)
Central Nervous System Infections/complications , Central Nervous System Infections/diagnostic imaging , Diagnostic Errors/prevention & control , Diagnostic Imaging/methods , Hematologic Neoplasms/complications , Neuroimaging/methods , Brain/diagnostic imaging , Diagnosis, Differential , Humans
3.
Immunooncol Technol ; 5: 10-21, 2020 Mar.
Article in English | MEDLINE | ID: mdl-35756142

ABSTRACT

Immunotherapy has changed the treatment landscape for many cancers; however, not all patients treated have a favorable response and others can develop immune-related adverse events. A method to predict the treatment response to immunotherapeutic agents could allow for improved selection of patients more likely to benefit from treatment while sparing those who would suffer serious complications. While this has been an active area of research and has resulted in significant insights, current proposed mechanisms do not fully explain responses to therapy. One problem is that our understanding relies mostly on tumor biopsy samples that do not account for the complex spatiotemporal heterogeneity of cancers and their microenvironment. Radiolabeled probes targeting immune biomarkers and imaged using positron emission tomography with computed tomography could provide in vivo, real-time and non-invasive imaging of these biomarkers. Here we review the current field of functional nuclear imaging agents in immuno-oncology including antibodies and small molecule tracers to image PD-1, PD-L1, CTLA-4, T-cell markers and other targets being studied for potential therapies.

8.
Arch Virol ; 152(11): 2005-16, 2007.
Article in English | MEDLINE | ID: mdl-17680326

ABSTRACT

An outbreak of acute hemorrhagic conjunctivitis (AHC) was reported in Singapore military camps in the year 2005. A total of 103 conjunctival swab specimens were collected from military personnel diagnosed clinically with AHC. PCR testing on these conjunctival specimens revealed the presence of an enterovirus, and this was confirmed by virus isolation. Molecular typing using a partial VP1 gene confirmed a variant of coxsackievirus A24 (CA24v) as the most likely etiological agent for the outbreak. Full-length genome sequencing was carried out on 2 selected virus strains, DSO-26SIN05 and DSO-52SIN05. Sequence comparison and phylogenetic analyses of the VP4, VP1 and 3Cpro gene regions were performed, clustering the Singapore CA24v strains with viruses originating from Asia in the post-2000 era. In addition, we report evolution rates of 4.2 x 10(-3) and 1.0 x 10(-3) nucleotide/year, respectively, for the VP4 capsid and 3Cpro gene regions. Our result shows a focal evolutionary point around 1965-1966, suggesting that the CA24v virus has been evolving constantly since its emergence in Singapore, nearly 40 years ago.


Subject(s)
Conjunctivitis, Acute Hemorrhagic/epidemiology , Coxsackievirus Infections/epidemiology , Disease Outbreaks , Enterovirus C, Human/classification , Enterovirus C, Human/isolation & purification , Military Personnel , 3C Viral Proteases , Capsid Proteins/genetics , Conjunctiva/virology , Conjunctivitis, Acute Hemorrhagic/virology , Coxsackievirus Infections/virology , Cysteine Endopeptidases/genetics , Enterovirus C, Human/genetics , Evolution, Molecular , Humans , Molecular Sequence Data , Phylogeny , Sequence Analysis, DNA , Singapore/epidemiology , Viral Proteins/genetics
9.
Biotechnol Bioeng ; 84(3): 382-9, 2003 Nov 05.
Article in English | MEDLINE | ID: mdl-12968292

ABSTRACT

We analyze the dynamics of a spherical scaffold in rotating bioreactors (or clinostats). The idealized clinostat environment consists of a purely rotational flow that is perpendicular to a gravitational field. We confirm through a detailed analytical study that lift effects considerably alter the position of the equilibrium point reached by the scaffolds in the (vertical) direction collinear to the gravitational field. This result holds for small particle and shear Reynolds numbers. Our analysis shows that the inertial lift effect is negligible in the horizontal direction. We show that for all rotations of practical interest, and for the range of particle Reynolds number smaller than unity, the vertical coordinate of the equilibrium point is strongly affected by consideration of lift effects. For light (heavy) particles, inclusion of lift in the formation forces the equilibrium position to be below (above) the horizontal plane that contains the axis of rotation. The equilibrium point for light particles is stable and therefore is observable experimentally. The equilibrium point for heavy particles is unstable. We also estimate the stress level applied to the scaffold and derive an algebraic expression that indicates that the stress level acting on the scaffold decreases with increasing shear Reynolds number.


Subject(s)
Bioreactors , Cell Physiological Phenomena , Extracellular Matrix/physiology , Mechanotransduction, Cellular/physiology , Models, Biological , Physical Stimulation/methods , Rheology/methods , Rotation , Acceleration , Cell Culture Techniques/methods , Cells, Cultured , Computer Simulation , Membranes, Artificial , Physical Stimulation/instrumentation , Shear Strength , Stress, Mechanical
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