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1.
J Neurol ; 269(12): 6582-6588, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35997818

RESUMO

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.


Assuntos
Transtornos do Olfato , Siderose , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Olfato , Transtornos do Olfato/diagnóstico por imagem , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Siderose/complicações , Siderose/diagnóstico por imagem , Siderose/epidemiologia , Cognição , Sistema Nervoso Central
2.
Clin Radiol ; 76(6): 470.e1-470.e12, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33610289

RESUMO

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.


Assuntos
Infecções do Sistema Nervoso Central/complicações , Infecções do Sistema Nervoso Central/diagnóstico por imagem , Erros de Diagnóstico/prevenção & controle , Diagnóstico por Imagem/métodos , Neoplasias Hematológicas/complicações , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Diagnóstico Diferencial , Humanos
3.
Immunooncol Technol ; 5: 10-21, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35756142

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-17680326

RESUMO

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.


Assuntos
Conjuntivite Hemorrágica Aguda/epidemiologia , Infecções por Coxsackievirus/epidemiologia , Surtos de Doenças , Enterovirus Humano C/classificação , Enterovirus Humano C/isolamento & purificação , Militares , Proteases Virais 3C , Proteínas do Capsídeo/genética , Túnica Conjuntiva/virologia , Conjuntivite Hemorrágica Aguda/virologia , Infecções por Coxsackievirus/virologia , Cisteína Endopeptidases/genética , Enterovirus Humano C/genética , Evolução Molecular , Humanos , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Singapura/epidemiologia , Proteínas Virais/genética
9.
Biotechnol Bioeng ; 84(3): 382-9, 2003 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-12968292

RESUMO

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.


Assuntos
Reatores Biológicos , Fenômenos Fisiológicos Celulares , Matriz Extracelular/fisiologia , Mecanotransdução Celular/fisiologia , Modelos Biológicos , Estimulação Física/métodos , Reologia/métodos , Rotação , Aceleração , Técnicas de Cultura de Células/métodos , Células Cultivadas , Simulação por Computador , Membranas Artificiais , Estimulação Física/instrumentação , Resistência ao Cisalhamento , Estresse Mecânico
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