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1.
Artigo em Inglês | MEDLINE | ID: mdl-34590504

RESUMO

Background: An ongoing longitudinal study in six European sites includes a 3-monthly assessment of forced vital capacity (FVC), slow vital capacity (SVC), peak cough flow (PCF), and Sniff nasal inspiratory pressure (SNIP). The aim of this interim analysis was to assess the potential for SNIP to be a surrogate for aerosol generating procedures given COVID-19 related restrictions. Methods: This was a prospective observational study. Patients attending six study sites with King's Stage 2 or 3 ALS completed baseline FVC/SVC/SNIP/PCF and repeated assessments 3 monthly. Data were collected from March 2018 to March 2020, after which a COVID-19 related study suspension was imposed. Correlations between the measures were calculated. A Bayesian multiple outcomes random-effects model was constructed to investigate rates of decline across measures. Results: In total, 270 cases and 828 assessments were included (Mean age 65.2 ± 15.4 years; 32.6% Female; 60% Kings stage 2; 81.1% spinal onset). FVC and SVC were the most closely correlated outcomes (0.95). SNIP showed the least correlation with other metrics 0.53 (FVC), 0.54 (SVC), 0.60 (PCF). All four measures significantly declined over time. SNIP in the bulbar onset group showed the fastest rate of decline. Discussion: SNIP was not well correlated with FVC and SVC, probably because it examines a different aspect of respiratory function. Respiratory measures declined over time, but differentially according to the site of onset. SNIP is not a surrogate for FVC and SVC, but is a complementary measure, declining linearly and differentiating spinal and bulbar onset patients.


Assuntos
Esclerose Amiotrófica Lateral , COVID-19 , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/diagnóstico , Teorema de Bayes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Capacidade Vital
2.
Artigo em Inglês | MEDLINE | ID: mdl-31313597

RESUMO

Objective: Sniff nasal inspiratory pressure (SNIP) is a commonly used clinical measure of respiratory impairment in amyotrophic lateral sclerosis (ALS), which is used to guide the initiation of noninvasive ventilation (NIV). SNIP can be completed with either an occluded or an un-occluded contralateral nostril. The aim of this study was to compare occluded and un-occluded SNIP measurements and to examine the decline in occluded SNIP over time compared to the ALSFRS-R respiratory subscore. Methods: This was a prospective longitudinal study examining occluded and un-occluded SNIP scores in ALS and PLS patients recorded between 2001 and 2018. Bland and Altman graphs were plotted for occluded vs. un-occluded SNIP measurements taking account of the repeated measures nature of the data. Longitudinal models were constructed as linear mixed effects multi-level models with follow-up in ALS limited to 6 years. Results: SNIP measured with an occluded contralateral nostril was systematically higher than with an un-occluded nostril. SNIP measured using both methods declined non-linearly, particularly after 2-3 years. The best fit model for decline in occluded SNIP included a main effect and interaction between site of onset and time, with age and diagnostic delay as independent variables. This showed a linear decline in spinal onset with a floor effect in bulbar-onset ALS. Conclusion: SNIP measured with an occluded and un-occluded contralateral nostril is not interchangeable, which is relevant in interpreting thresholds for initiation of NIV. SNIP declines non-linearly, which is explained in spinal onset ALS by age and diagnostic delay, but an apparent floor effect remains in bulbar onset.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico , Diagnóstico Tardio/prevenção & controle , Doença dos Neurônios Motores/diagnóstico , Insuficiência Respiratória/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Músculos Respiratórios
3.
Infect Genet Evol ; 9(4): 493-500, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19460314

RESUMO

Candida albicans is a major opportunistic pathogen of humans. Previous work has demonstrated the existence of a general-purpose genotype (GPG; equivalent to clade 1 as defined by multi-locus sequence typing data) that is more frequent than other genotypes as an agent of human disease and commensal colonization. We undertook a genomic screen which indicated that a large number of mutations differentiate GPG strains from other strains and that such mutations are scattered throughout the genome. GPG-specific mutations are non-synonymous more frequently than expected by chance, and are not randomly distributed across functional and structural gene categories. Our analysis has identified three categories of genes in which GPG-specific mutations are over-represented, namely genes for which expression changes during the yeast-hyphal transition, genes for which expression changes as a result of exposure to antifungal agents and repeat-containing ORFs. Although we have no direct evidence that the individual polymorphisms identified confer selective advantages to GPG strains, the results support our contention that the high prevalence of GPG strains is not merely due to genetic drift but that GPG strains have reached a high prevalence because they possess a multitude of fitness-enhancing traits. They also indicate that the distribution of genes marked by GPG-specific mutations across functional and structural categories could identify physiological traits that are of particular importance to the success of GPG strains in their interactions with the human host.


Assuntos
Candida albicans/genética , Candida albicans/patogenicidade , Candidíase/microbiologia , Genoma Fúngico , Polimorfismo Genético , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , DNA Fúngico , Interpretação Estatística de Dados , Genes Fúngicos , Genótipo , Humanos , Dados de Sequência Molecular , Mutação , Fases de Leitura Aberta , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
4.
Genome Res ; 13(9): 2005-17, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12952872

RESUMO

The ALS (agglutinin-like sequence) gene family encodes proteins that play a role in adherence of the yeast Candida albicans to endothelial and epithelial cells. The proteins are proposed as virulence factors for this important fungal pathogen of humans. We analyzed 66 C. albicans strains, representing a worldwide collection of 266 infection-causing isolates, and discovered 60 alleles of the ALS7 open reading frame (ORF). Differences between alleles were largely caused by rearrangements of repeat elements in the so-called tandem repeat domain (21 different types occurred) and the VASES region (19 different types). C. albicans is diploid, and combinations of ALS7 alleles generated 49 different genotypes. ALS7 expression was detected in samples isolated directly from five oral candidosis patients. ORFs in the opposite direction contained within the ALS7 ORF were also transcribed in all strains tested. Isolates representing a more pathogenic general-purpose genotype (GPG) cluster of strains tended to have more tandem repeats than other strains. Two types of VASES regions were largely exclusive to GPG strains; the remaining types were largely exclusive to noncluster strains. Our results provide evidence that ALS7 is a hypermutable contingency locus and important for the success of C. albicans as an opportunistic pathogen of humans.


Assuntos
Alelos , Candida albicans/genética , Proteínas Fúngicas/genética , Marcadores Genéticos , Glicoproteínas de Membrana/genética , Mutação , Fases de Leitura Aberta/genética , Sequência Conservada/genética , Proteínas Fúngicas/biossíntese , Regulação Fúngica da Expressão Gênica/genética , Variação Genética , Genótipo , Glicoproteínas de Membrana/biossíntese , Dados de Sequência Molecular , Família Multigênica , Polimorfismo de Fragmento de Restrição , RNA Mensageiro/análise , Especificidade da Espécie , Sequências de Repetição em Tandem/genética
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