RESUMO
Shiga toxin-producing Escherichia coli (STEC) are widely detected in raw milk products intended for human consumption. Although STEC are a worldwide public health problem, the pathogenicity of STEC in cheese remains unclear. In fact, bacterial association with compounds in raw milk cheeses could reduce their pathogenicity. A previous study showed the association of 2 STEC strains with raw milk cream in a natural creaming assay. Different concentrations of each strain were required to saturate the cream. In this study, we hypothesized that all STEC strains could be associated with milk fat globules (MFG) in raw milk and that the bacterial load required for saturation of the cream is serotype dependent. We evaluated the affinity of STEC strains belonging to the O157:H7, O26:H11, and O103:H2 serotypes for bovine raw milk cream and analyzed saturation of the cream layer by natural creaming assay. We used 12 STEC strains and 3 strains belonging to another pathotype to assess the effects of serotypes on this phenomenon. We performed sucrose density gradient centrifugation assays with 2 STEC model strains to confirm the results obtained by natural creaming. The localization of STEC within MFG-enriched creams was observed by confocal and electron microscopy. We recovered approximately 10 times more STEC from the cream layer after natural creaming than from raw bovine milk. The concentration of STEC required to saturate the cream layer (the saturation concentration) was estimated for each strain by nonlinear regression, highlighting a strain and serotype effect. Moreover, the concentration of STEC in the cream was milk fat level dependent. However, even in nonsaturating conditions, a high level of STEC was still present in the aqueous phase, after fat separation. Thus, natural creaming should not be used as the sole preventive measure to remove STEC from naturally contaminated raw milk. The results of our study suggest that cream saturation is a complex mechanism, most likely involving specific interactions between STEC and raw MFG.
Assuntos
Proteínas de Escherichia coli , Escherichia coli Shiga Toxigênica , Humanos , Animais , Sorogrupo , Proteínas de Escherichia coli/genética , SacaroseRESUMO
El objetivo de este artículo es presentar una alternativa de tratamiento rehabilitador para pacientes jóvenes con gran pérdida de estructura dental vinculada a lesiones de origen no bacteriano. Se presenta el caso clínico de un paciente de 36 años de edad, con reflujo gastroesofágico crónico bajo tratamiento médico, que concurrió a la Cátedra de Odontología Integral Adultos de la Facultad de Odontología de la Universidad de Buenos Aires (FOUBA), en busca de un cambio estético en su sonrisa y relatando sensibilidad al calor, al frío y dolor al masticar. No manifestó sintomatología dolorosa a nivel muscular ni articular. En función de sus posibilidades económicas y de la etiología erosiva de las lesiones existentes en sus piezas dentarias, se llevó a cabo una rehabilitación oral adhesiva con resinas compuestas utilizando la sistematización de atención que sugiere la Cátedra. Las resinas compuestas actuales, en combinación con las técnicas y procedimientos desarrollados en este artículo han demostrado un adecuado comportamiento al ser utilizadas como restauraciones definitivas en pacientes que necesitan rehabilitación oral total debido a la gran pérdida de estructura dental por erosión ácida (AU)
Assuntos
Humanos , Masculino , Adulto , Erosão Dentária/terapia , Colagem Dentária , Resinas Compostas/uso terapêutico , Argentina , Faculdades de Odontologia , Refluxo Gastroesofágico/complicações , Restauração Dentária Permanente/métodos , Reabilitação BucalRESUMO
El objetivo de este artículo es presentar una alternativa de tratamiento rehabilitador para pacientes jóvenes con gran pérdida de estructura dental, vinculada a lesiones de origen no bacteriano. Se presenta el caso clínico de un paciente de sexo masculino, de 39 años de edad, que acudió a la Cátedra de Odontología Integral Adultos de la Facultad de Odontología de la Universidad de Buenos Aires (FOUBA) relatando síntomas compatibles con hipersensibilidad dentaria y fatiga de los músculos masticadores. Al mismo tiempo, manifestó disconformidad con el aspecto estético de su sonrisa. Teniendo en cuenta la gran pérdida de sustancia en sus piezas dentarias producida por hábitos parafuncionales (bruxismo), se realizó una rehabilitación oral adhesiva con cerámicas utilizando el protocolo de abordaje terapéutico sugerido por la Cátedra. En pacientes que presentan severos desgastes (AU)
Assuntos
Humanos , Masculino , Adulto , Erosão Dentária/terapia , Bruxismo/terapia , Estética Dentária , Argentina , Faculdades de Odontologia , Sorriso , Cerâmica , Colagem Dentária/métodos , Músculos da Mastigação/fisiopatologia , Reabilitação BucalRESUMO
STUDY DESIGN: Prospective clinical cohort study (data collection); expert opinion (recommendation development). OBJECTIVES: Treatment options for nonsurgical and surgical management of osteoporotic vertebral body fractures differ widely. Based on the current literature, the knowledge of the experts, and their classification for osteoporotic fractures (OF classification), the Spine Section of the German Society for Orthopaedics and Trauma has now introduced general treatment recommendations. METHODS: A total of 707 clinical cases from 16 hospitals were evaluated. An OF classification-based score was developed for guidance in the option of nonsurgical versus surgical management. For every classification type, differentiated treatment recommendations were deduced. Diagnostic prerequisites for reproducible treatment recommendations were defined: conventional Xrays with consecutive follow-up images (standing position whenever possible), magnetic resonance imaging, and computed tomography scans. OF classification allows for upgrading of fracture severity during the course of radiographic follow-up. The actual classification type is decisive for the score. RESULTS: A score of less than 6 points advocates nonsurgical management; in cases with more than 6 points, surgical management is recommended. The primary goal of treatment is fast and painless mobilization. Because of the expected comorbidities in this age group, minimally invasive procedures are preferred. As a general rule, stability is more important than motion preservation. It is mandatory to restore the physiological loading capacity of the spine. If the patient was in a compensated unbalanced state at the time of fracture, reconstruction of the individual prefracture sagittal profile is sufficient. The instrumentation technique has to account for compromised bone quality. We recommend the use of cement augmentation or high purchase screws. The particular situations of injuries with neurological impairment, the necessity to fuse, multiple level fractures, consecutive and adjacent fractures and fractures in ankylosing spondylitis are addressed separately. CONCLUSIONS: The therapeutic recommendations presented here provide a reliable and reproducible basis to decide for the treatment choices available. However, intermediate clinical situations with a score of 6 points remain, allowing for both nonsurgical and surgical options. As a result, individualized treatment decisions may still be necessary. In the subsequent step, the recommendations presented will be further evaluated in a multicentre controlled clinical trial.
Assuntos
Ortopedia , Fraturas por Osteoporose , Estudos de Coortes , Fraturas por Compressão , Humanos , Estudos Prospectivos , Fraturas da Coluna Vertebral , Resultado do TratamentoRESUMO
OBJECTIVES: Dopaminergic degeneration affects both nigrostriatal projection neurons and retinal amacrine cells in Parkinson disease (PD). Parkinsonian retinopathy is associated with impaired color discrimination and contrast sensitivity. Some prior studies described associations between color discrimination deficits and cognitive deficits in PD, suggesting that contrast discrimination deficits are due, at least in part, to cognitive deficits in PD. We investigated the relationship between cognitive deficits and impaired contrast sensitivity in PD. METHODS: PD subjects, n = 43; 15F/28M; mean age 66.5 ± 8.2, Hoehn and Yahr stage 2.6 ± 0.6, and duration of disease of 6.2 ± 5.0 years underwent neuropsychological and Rabin contrast sensitivity testing. RESULTS: Mean Rabin contrast sensitivity score was 1.34 ± 0.40. Bivariate analyses showed significant correlation between Rabin contrast sensitivity scores and global cognitive z-scores (R = 0.54, P = 0.0002). Cognitive domain Z-score post hoc analysis demonstrated most robust correlation between Rabin scores and executive functions (R = 0.49, P = 0.0009), followed by verbal learning (R = 0.44, P = 0.0028), visuospatial (R = 0.39, P = 0.001) and attention z-scores (R = 0.32, P = 0.036). CONCLUSIONS: Impaired contrast sensitivity in PD is robustly associated with cognitive deficits, particularly executive function deficits. These results suggest that contrast sensitivity may be a useful biomarker for cognitive changes in PD and may have implications for driving safety evaluations in PD.
Assuntos
Transtornos Cognitivos/etiologia , Sensibilidades de Contraste/fisiologia , Função Executiva/fisiologia , Doença de Parkinson/complicações , Transtornos de Sensação/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa , Índice de Gravidade de Doença , Aprendizagem Verbal/fisiologiaRESUMO
RATIONALE AND OBJECTIVES: Parkinson disease (PD) is a progressive neurodegenerative disorder affecting motor and cognitive functions. Prior studies showed that patients with PD and diabetes (DM) demonstrate worse clinical outcomes compared to nondiabetic subjects with PD. Our study aimed at defining the relationship between DM, gray matter volume, and cognition in patients with PD. MATERIALS AND METHODS: This study included 36 subjects with PD (12 with DM, 24 without DM, mean age = 66). Subjects underwent high-resolution T1-weighted brain magnetic resonance imaging, [(11)C]dihydrotetrabenazine positron emission tomography imaging to quantify nigrostriatal dopaminergic denervation, clinical, and cognitive assessments. Magnetic resonance images were postprocessed to determine total and lobar cortical gray matter volumes. Cognitive testing scores were converted to z-scores for specific cognitive domains and a composite global cognitive z-score based on normative data computed. Analysis of covariance, accounting for effects of age, gender, intracranial volume, and striatal [(11)C]dihydrotetrabenazine binding, was used to test the relationship between DM and gray matter volumes. RESULTS: Impact of DM on total gray matter volume was significant (P = 0.02). Post hoc analyses of lobar cortical gray matter volumes revealed that DM was more selectively associated with lower gray matter volumes in the frontal regions (P = 0.01). Cognitive post hoc analyses showed that interaction of total gray matter volume and DM status was significantly associated with composite (P = 0.007), executive (P = 0.02), and visuospatial domain cognitive z-scores (P = 0.005). These associations were also significant for the frontal cortical gray matter. CONCLUSION: DM may exacerbate brain atrophy and cognitive functions in PD with greater vulnerability in the frontal lobes. Given the high prevalence of DM in the elderly, delineating its effects on patient outcomes in the PD population is of importance.
Assuntos
Encefalopatias/complicações , Cognição/fisiologia , Complicações do Diabetes , Substância Cinzenta/patologia , Doença de Parkinson/complicações , Idoso , Atrofia , Atenção/fisiologia , Gânglios da Base/diagnóstico por imagem , Radioisótopos de Carbono , Estudos de Casos e Controles , Estudos Transversais , Neurônios Dopaminérgicos/patologia , Função Executiva/fisiologia , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico por imagem , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Tetrabenazina/análogos & derivadosRESUMO
Mild to moderate Parkinson's disease shows more denervation in the posterodorsal striatum and sparing of the anteroventral striatum. Dopaminergic medications can interfere with anteroventral striatum function by overdosing this relatively intact structure. The authors determined how regional striatal denervation affects medication-associated sequence learning impairment in Parkinson's disease. Eighteen Parkinson's patients performed motor sequence learning on and off levodopa. Patients underwent (11)C-dihydrotetrabenazine positron emission tomography scans to measure nigrostriatal denervation. Patients with more preserved putamen were more likely to exhibit levodopa-associated sequence learning impairments. Furthermore, the ratio of denervation in the anterior to posterior dorsal putamen predicted the level of learning differences on and off levodopa. These results demonstrate that the spatial pattern of nigrostriatal dopaminergic denervation predicts medication responsiveness for motor sequence learning.
Assuntos
Antiparkinsonianos/uso terapêutico , Denervação , Levodopa/uso terapêutico , Neostriado/patologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Aprendizagem Seriada/fisiologia , Idoso , Interpretação Estatística de Dados , Feminino , Radioisótopos de Flúor , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tetrabenazina/análogos & derivadosRESUMO
Variants in genes regulating dopamine transmission affect performance on tasks including working memory and executive function as well as temporal processing and sequence learning. In the current study, we determined whether a dopamine D2 receptor DNA sequence polymorphism interacts with L-DOPA during motor tasks in patients with Parkinson's disease (PD). Forty-five PD patients were genotyped for the DRD2 polymorphism (rs 1076560, G>T). Patients performed an explicit motor sequence learning task and the grooved pegboard test in both ON and OFF L-DOPA states. For motor sequence learning, DRD2 genotype mediated L-DOPA effects such that L-DOPA associated improvements were only observed in the minor T allele carriers (associated with lower D2 receptor availability, t10=-2.71, p=0.022), whereas G homozygotes showed no performance change with L-DOPA. For the grooved pegboard test, performance improved with L-DOPA independent of patients' DRD2 genotype. Collectively these results demonstrate that common DRD2 allelic differences found in the human population may explain how dopamine differentially contributes to performance across tasks and individuals.
Assuntos
Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Polimorfismo Genético/genética , Receptores de Dopamina D2/genética , Idoso , Alelos , Interpretação Estatística de Dados , Dopamina/metabolismo , Feminino , Genótipo , Heterozigoto , Humanos , Aprendizagem/fisiologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologiaRESUMO
Analysis of the amplitude of low frequency BOLD signal fluctuations (ALFF) in the resting state has recently been used to study the dynamics of intrinsic neural activity. Several studies have also suggested its potential as a biomarker for neuropsychiatric disease. In the current study, we quantified ALFF to determine changes in intrinsic neural oscillations in patients with Parkinson's disease (PD) on and off L-DOPA. Twenty-four PD patients and 24 healthy age-matched controls participated in the study. PD patients underwent two resting state fMRI sessions, either ON a controlled dose of L-DOPA or following a placebo pill (OFF). Control participants underwent one test session. We found that there was increased amplitude of low frequency BOLD signal oscillations for PD patients OFF L-DOPA in the primary and secondary motor areas, and in the middle and medial prefrontal cortices. L-DOPA significantly reduced the amplitude of low frequency oscillations within these regions. The degree of ALFF in the premotor cortex predicted patients' motor performance as measured by the Grooved Pegboard task, such that greater ALFF was associated with poorer performance. These results are in line with the pathophysiology of PD, which shows changes in neural oscillations. Thus, frequency domain analyses of resting state BOLD fMRI signals may provide a useful means to study the pathophysiology of PD and the physiology of the brain's dopaminergic pathways.
RESUMO
The aim of the present study was to predict Clostridium perfringens vegetative cell inactivation during the final reheating step of two beef-in-sauce products prepared and distributed in a French hospital for exposure in risk assessment. In order to account for variability according to experts and international organization recommendations, published data were used to estimate the thermal inactivation parameters of a probabilistic model. Mixed effects models were proposed to describe variability on D(ref) the decimal reduction time at temperature T(ref). Many models differing by their description of variability on D(ref) were tested. Based on goodness-of-fit and parsimony of the model, the one including three random effects was chosen. That model describes random effects of vegetative cell culture conditions, strains and other uncontrolled experimental factors. In order to check the ability of the model to predict inactivation under dynamic thermal conditions, model validation was carried out on published non isothermal data. This model was then used to predict C. perfringens vegetative cell inactivation using temperature profiles inside beef-in-sauce products registered in a French hospital and to explore control measures easier to apply than French regulations.
Assuntos
Clostridium perfringens/crescimento & desenvolvimento , Manipulação de Alimentos , Modelos Lineares , Produtos da Carne/microbiologia , Clostridium perfringens/isolamento & purificação , Contagem de Colônia Microbiana , Alimentos , Contaminação de Alimentos , Microbiologia de Alimentos , Conservação de Alimentos , Previsões , Temperatura Alta , Humanos , Carne , Modelos Biológicos , Modelos Estatísticos , Esporos Bacterianos/fisiologiaRESUMO
The present study backcalculated body length for a data set of a bullhead Cottus gobio population located at different sampling sites in a river network. Model comparison between various growth models, which included successively new parameters, showed the effect and importance of taking sex, age and the location in the river network into account. The data sets obtained by backcalculation were fitted by the von Bertalanffy growth function, which revealed the effect of the backcalculation formula on the estimation of the von Bertalanffy growth parameters. Fitting results and parameter estimates showed again the importance of incorporating age and sex when backcalculating body length in the C. gobio population studied.
Assuntos
Tamanho Corporal , Peixes/anatomia & histologia , Fatores Etários , Animais , Feminino , Peixes/crescimento & desenvolvimento , Peixes/fisiologia , Masculino , Modelos Biológicos , Fatores SexuaisRESUMO
BACKGROUND: Water-filtered infrared A (wIRA) radiation can improve the healing of acute and chronic wounds both by thermal and thermic as well as by nonthermal and nonthermic effects. wIRA increases tissue temperature, oxygen partial pressure and perfusion. OBJECTIVES: Investigation of the influence of wIRA on chronic venous stasis ulcers in an investigator-initiated, randomized, controlled, blinded study. METHODS: Fifty-one patients with nonhealing chronic venous stasis ulcers of the lower legs were treated with compression therapy, wound cleansing, nonadhesive wound dressings and 30 min irradiation [wIRA + visible light (VIS) or VIS alone], predominantly at home, five times per week over 9 weeks and an additional 4 weeks without irradiation. RESULTS: Compared with the control group with VIS alone, the group with wIRA + VIS showed better wound healing [after 9 weeks 85 vs. 67·5 on a 0-100 visual analogue scale (VAS), median difference 15, 95% confidence interval (CI) 3-30, P = 0·012], a higher percentage of patients with a healing trend [after 9 weeks 21 of 25 (84%) vs. 13 of 26 (50%), P = 0·023], better granulation (after 9 weeks 90 vs. 80 on a 0-100 VAS, median difference 10, 95% CI 0-30, P = 0·036), a trend to less exudation (after 5 weeks 30 vs. 55 on a 0-100 VAS, P = 0·075) and to faster reduction of the wound area (after 7 weeks 39% vs. 19·5% reduction of wound area, median difference 20·5%, 95% CI -4-49%, P = 0·10; for wounds with an initial area < 10 cm(2): after 13 weeks 92% vs. 47% reduction of wound area, median difference 30%, 95% CI 0-68%, P = 0·11). The main variable 'Integral of relative ulcer area for each individual patient over time, standardized to an initial size of 1' did not reach significance. The application of wIRA at home was easily manageable. CONCLUSIONS: For the treatment of chronic venous stasis ulcers, the application of wIRA combined with phlebological therapy, compression therapy and wound dressing can be useful and can be recommended.
Assuntos
Raios Infravermelhos/uso terapêutico , Úlcera Varicosa/terapia , Idoso , Idoso de 80 Anos ou mais , Sangria/métodos , Doença Crônica , Método Duplo-Cego , Feminino , Filtração , Serviços de Assistência Domiciliar , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Água , CicatrizaçãoRESUMO
Models on Clostridium perfringens growth which have been published to date have all been deterministic. A probabilistic model describing growth under non-isothermal conditions was thus proposed for predicting C. perfringens growth in beef-in-sauce products cooked and distributed in a French hospital. Model parameters were estimated from different types of data from various studies. A Bayesian approach was proposed to model the overall uncertainty regarding parameters and potential variability on the 'work to be done' (h(0)) during the germination, outgrowth and lag phase. Three models which differed according to their description of this parameter h(0) were tested. The model with inter-curve variability on h(0) was found to be the best one, on the basis of goodness-of-fit assessment and validation with literature data on results obtained under non-isothermal conditions. This model was used in two-dimensional Monte Carlo simulations to predict C. perfringens growth throughout the preparation of beef-in-sauce products, using temperature profiles recorded in a hospital kitchen. The median predicted growth was 7.8×10(-2) log(10) cfu·g(-1) (95% credibility interval [2.4×10(-2), 0.8]) despite the fact that for more than 50% of the registered temperature profiles cooling steps were longer than those required by French regulations.
Assuntos
Clostridium perfringens/crescimento & desenvolvimento , Conservação de Alimentos/métodos , Produtos da Carne/microbiologia , Modelos Biológicos , Teorema de Bayes , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , Culinária/métodos , Manipulação de Alimentos/métodos , Humanos , Cinética , Método de Monte Carlo , Valor Preditivo dos Testes , TemperaturaRESUMO
OBJECTIVES: The increasing amount of electronically available documents in bibliographic databases and the clinical documentation requires user-friendly techniques for content retrieval. METHODS: A domain-specific approach on semantic text indexing for document retrieval is presented. It is based on a subword thesaurus and maps the content of texts in different European languages to a common interlingual representation, which supports the search across multilingual document collections. RESULTS: Three use cases are presented where the semantic retrieval method has been implemented: a bibliographic database, a department EHR system, and a consumer-oriented Web portal. CONCLUSIONS: It could be shown that a semantic indexing and retrieval approach, the performance of which had already been empirically assessed in prior studies, proved useful in different prototypical and routine scenarios and was well accepted by several user groups.
Assuntos
Armazenamento e Recuperação da Informação/métodos , Multilinguismo , Semântica , Bases de Dados Bibliográficas , Europa (Continente) , Informática MédicaRESUMO
OBJECTIVE: To investigate the relationships between history of falls and cholinergic vs dopaminergic denervation in patients with Parkinson disease (PD). BACKGROUND: There is a need to explore nondopaminergic mechanisms of gait control as the majority of motor impairments associated with falls in PD are resistant to dopaminergic treatment. Alterations in cholinergic neurotransmission in PD may be implicated because of evidence that gait control depends on cholinergic system-mediated higher-level cortical and subcortical processing, including pedunculopontine nucleus (PPN) function. METHODS: In this cross-sectional study, 44 patients with PD (Hoehn & Yahr stages I-III) without dementia and 15 control subjects underwent a clinical assessment and [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [(11)C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 (VMAT2) brain PET imaging. RESULTS: Seventeen patients (38.6%) reported a history of falls and 27 patients had no falls. Analysis of covariance of the cortical AChE hydrolysis rates demonstrated reduced cortical AChE in the PD fallers group (-12.3%) followed by the PD nonfallers (-6.6%) compared to control subjects (F = 7.22, p = 0.0004). Thalamic AChE activity was lower only in the PD fallers group (-11.8%; F = 4.36, p = 0.008). There was no significant difference in nigrostriatal dopaminergic activity between PD fallers and nonfallers. CONCLUSIONS: Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD.
Assuntos
Acidentes por Quedas , Acetilcolinesterase/metabolismo , Encéfalo/fisiopatologia , Doença de Parkinson/fisiopatologia , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiopatologia , Estudos Transversais , Dopamina/metabolismo , Feminino , Humanos , Hidrólise , Cinética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Substância Negra/diagnóstico por imagem , Substância Negra/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologiaRESUMO
BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a severe genetic skin blistering disorder caused by mutations in the gene COL7A1, encoding collagen VII. Recently, the MMP1 promoter single nucleotide polymorphism (SNP) rs1799750, designated as 1G 2G, was shown to be involved in modulation of disease severity in patients with recessive DEB (RDEB), and was proposed as a genetic modifier. OBJECTIVES: To identify the molecular basis of DEB in 103 individuals and to replicate the results of the MMP1 promoter SNP analysis in an independent patient group, as verification is necessary in such a rare and heterogeneous disorder. METHODS: To determine the molecular basis of the disease, we performed COL7A1 mutation screening, reverse transcription-polymerase chain reaction (PCR) and real-time quantitative PCR. The status of the MMP1 SNP was analysed by PCR and restriction enzyme digestion and verified by sequencing. RESULTS: We disclosed 42 novel COL7A1 mutations, including the first large genomic deletion of 4 kb affecting only the COL7A1 gene, and three apparently silent mutations affecting splicing. Even though the frequency of the high-risk allele was increased in patients with RDEB, no statistically significant correlation between disease severity and genotype could be made. Also, no correlation was observed with development of squamous cell carcinoma, a severe complication of DEB. CONCLUSIONS: Taken together, the results suggest that the MMP1 SNP is not the sole disease modifier in different forms of DEB, and other genetic and environmental factors contribute to the clinical phenotype.
Assuntos
Códon sem Sentido/genética , Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica , Metaloproteinase 1 da Matriz/genética , Mutação de Sentido Incorreto/genética , Regiões Promotoras Genéticas/genética , Estudos de Coortes , Análise Mutacional de DNA/métodos , Epidermólise Bolhosa Distrófica/enzimologia , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/patologia , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Sítios de Splice de RNA/genética , Análise de Sequência de DNA , População Branca/genéticaRESUMO
OBJECTIVE: To investigate the relationship between age-associated MRI leukoaraiosis or white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity. BACKGROUND: One possible mechanism of cognitive decline in elderly individuals with leukoaraiosis is disruption of cholinergic fibers by strategically located white matter lesions. Periventricular lesions may have a higher chance of disrupting cholinergic projections compared with more superficial nonperiventricular white matter lesions because of anatomic proximity to the major cholinergic axonal projection bundles that originate from the basal forebrain. METHODS: Community-dwelling, middle-aged and elderly subjects without dementia (mean age 71.0 +/- 9.2 years; 55-84 years; n = 18) underwent brain MRI and AChE PET imaging. The severity of periventricular and nonperiventricular WMH on fluid-attenuated inversion recovery MRI images was scored using the semiquantitative rating scale of Scheltens et al. [11C]methyl-4-piperidinyl propionate AChE PET imaging was used to assess cortical AChE activity. Age-corrected Spearman partial rank correlation coefficients were calculated. RESULTS: The severity of periventricular (R = -0.52, p = 0.04) but not nonperiventricular (R = -0.20, not significant) WMH was inversely related to global cortical AChE activity. Regional cortical cholinergic effects of periventricular WMH were most significant for the occipital lobe (R = -0.58, p = 0.02). CONCLUSIONS: The presence of periventricular but not nonperiventricular white matter hyperintensities (WMH) is significantly associated with lower cortical cholinergic activity. These findings support a regionally specific disruption of cholinergic projection fibers by WMH.
Assuntos
Envelhecimento/patologia , Córtex Cerebral/patologia , Fibras Colinérgicas/patologia , Transtornos Cognitivos/patologia , Leucoaraiose/patologia , Acetilcolina/metabolismo , Acetilcolinesterase/análise , Acetilcolinesterase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Núcleo Basal de Meynert/metabolismo , Núcleo Basal de Meynert/patologia , Núcleo Basal de Meynert/fisiopatologia , Biomarcadores/análise , Biomarcadores/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Fibras Colinérgicas/diagnóstico por imagem , Fibras Colinérgicas/metabolismo , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/metabolismo , Feminino , Humanos , Leucoaraiose/diagnóstico por imagem , Leucoaraiose/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Vias Neurais/patologia , Tomografia por Emissão de Pósitrons , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/patologiaRESUMO
Both pathogenic and nonpathogenic E. coli exhibit a stress response to sublethal environmental stresses. Several studies have reported acid tolerance and survival characteristics of E. coli O157:H7 in foodstuffs, but there are few reports about the tolerance of non-O157 serogroups (STEC) to organic acids in foods. The purpose of this study was to examine the effect of the manufacturing process of French fermented raw meat sausages on the growth and survival of acid-resistant (AR) and non-acid resistant (NAR) STEC strains. The six strains, 3 AR and 3 NAR, were inoculated separately into raw sausage mixture at a level of 10(4)-10(5) CFU/g. A total of 19 batches of sausages were manufactured. A rapid and similar decrease in the number of both AR and NAR STEC strains, from less than 1 to 1.5 log(10) CFU/g, was observed during the first 5 days of fermentation at 20-24 degrees C. This rapid decrease was followed by a more gradual but continuous decrease in STEC counts after drying at 13-14 degrees C, up to day 35. The STEC counts were <10 CFU/g after 35 days for the NAR strains and the same concentration for the AR strains on the best before date (day 60). It was not possible to detect any NAR STEC after 60 days. The present study shows that the process used in the manufacture of French sausages results in a complete destruction of NAR STEC strains after 60 days, but it does not have the same effect on the AR STEC strains.