An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors.

Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesized that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive Escherichia coli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation. Using IL10-/- mice, we found that NSAID aggravated colitis in AIEC-colonized animals. This was accompanied by activation of the NLRP3 inflammasome, Caspase-8, apoptosis, and pyroptosis, features not seen in mice exposed to AIEC or NSAID alone, revealing an AIEC/NSAID synergistic effect. Inhibition of NLRP3 or Caspase-8 activity ameliorated colitis, with reduction in NLRP3 inflammasome activation, cell death markers, activated T-cells and macrophages, improved histology, and increased abundance of Clostridium cluster XIVa species. Our findings provide new insights into how NSAIDs and an opportunistic gut-pathobiont can synergize to worsen IBD symptoms. Targeting the NLRP3 inflammasome or Caspase-8 could be a potential therapeutic strategy in IBD patients with gut inflammation, which is worsened by NSAIDs.

Total output and switching in ategory fluency successfully iscriminates Alzheimer's disease from Mild Cognitive Impairment, but not from frontotemporal dementia / Produção total e alternância discrimina com sucesso doença de Alzheimer de comprometimento cognitivo leve, mas não de demência frontotemporal

Verbal fluency tasks require generation of words beginning with a letter (phonemic fluency; PF) or from a category (category fluency; CF) within a limited time period. Generally, total output on CF has been used to discriminate Mild Cognitive Impairment (MCI) from Alzheimer's disease (AD), while poor PF has been used as a marker for behavioral-variant frontotemporal dementia (bvFTD). However, in the absence of this disparate performance, further characterization of the task becomes necessary.Objective:We examined whether fluency, as well as its components, clustering (successively generated words belonging to a category) and switching (shifting between categories) carried diagnostic utility in discriminating AD from MCI and bvFTD.Methods:PF (letter 'P') and CF ('animals') tasks were administered in English to patients with MCI (n=25), AD (n=37), and bvFTD (n=17). Clustering and switching scores were calculated using established criteria.Results:Our findings suggested that up to 85% of AD and MCI could be successfully discriminated based on total number of responses and switching in CF alone. PF-CF disparity was not noted in AD or bvFTD. Performance on clustering or switching also proved insufficient to discriminate AD from bvFTD.Conclusion:Switching was found to be useful when differentiating AD from MCI. In AD and bvFTD, the course of progression of the disease may lead to attenuation of total number of responses produced on both tasks to an extent where clustering and switching may not be useful measures to discriminate these dementias from each other.

Tarefas de fluência verbal requerem geração de palavras iniciadas por letras (fluência fonêmica; FF) ou por categoria (fluência por categoria; FC) dentro de um período limitado de tempo. Geralmente, a produção total na FC tem sido usada para discriminar o comprometimento cognitivo leve (CCL) da doença de Alzheimer, enquanto que, uma produção pobre em FF tem sido usada como marcador da variante comportamental da demência frontotemporal (vcDFT). Todavia, na ausência desta desproporção melhor caracterização torna-se necessária.Objetivo:Examinar se a fluência e seus componentes, agrupamentos (geração sucessiva de palavras pertencentes a uma categoria) e mudança (alternância entre categorias) teriam utilidade na discriminação entre DA, CCL e vcDFT.Métodos:Tarefas de FF (letra P) e FC (animais) foram administradas em inglês a pacientes com CCL (n=25), DA (n=37) e vcDFT (n=17). Escores de agrupamentos e alternância foram calculados através dos critérios estabelecidos.Resultados:Nossos achados sugeriram que 85% dos DA e CCL puderam ser discriminados com sucesso, baseando-se no número total de respostas e alternância na FC. A disparidade FF e FC não foi notada em DA ou vcDFT. O desempenho em agrupamento ou alternância também se provaram insuficientes para discriminar DA de vcDFT.Conclusão:Alternância foi útil na diferenciação DA de CCL. Em pacientes com DA e vcDFT a progressão das doenças podem levar à atenuação do número total de respostas produzidas em ambas as tarefas de modo que o agrupamento e alternância podem não ser medidas úteis na discriminação destas demências entre si.

Total output and switching in category fluency successfully discriminates Alzheimer's disease from Mild Cognitive Impairment, but not from frontotemporal dementia.

Verbal fluency tasks require generation of words beginning with a letter (phonemic fluency; PF) or from a category (category fluency; CF) within a limited time period. Generally, total output on CF has been used to discriminate Mild Cognitive Impairment (MCI) from Alzheimer's disease (AD), while poor PF has been used as a marker for behavioral-variant frontotemporal dementia (bvFTD). However, in the absence of this disparate performance, further characterization of the task becomes necessary. OBJECTIVE: We examined whether fluency, as well as its components, clustering (successively generated words belonging to a category) and switching (shifting between categories) carried diagnostic utility in discriminating AD from MCI and bvFTD. METHODS: PF (letter 'P') and CF ('animals') tasks were administered in English to patients with MCI (n=25), AD (n=37), and bvFTD (n=17). Clustering and switching scores were calculated using established criteria. RESULTS: Our findings suggested that up to 85% of AD and MCI could be successfully discriminated based on total number of responses and switching in CF alone. PF-CF disparity was not noted in AD or bvFTD. Performance on clustering or switching also proved insufficient to discriminate AD from bvFTD. CONCLUSION: Switching was found to be useful when differentiating AD from MCI. In AD and bvFTD, the course of progression of the disease may lead to attenuation of total number of responses produced on both tasks to an extent where clustering and switching may not be useful measures to discriminate these dementias from each other.

Tarefas de fluência verbal requerem geração de palavras iniciadas por letras (fluência fonêmica; FF) ou por categoria (fluência por categoria; FC) dentro de um período limitado de tempo. Geralmente, a produção total na FC tem sido usada para discriminar o comprometimento cognitivo leve (CCL) da doença de Alzheimer, enquanto que, uma produção pobre em FF tem sido usada como marcador da variante comportamental da demência frontotemporal (vcDFT). Todavia, na ausência desta desproporção melhor caracterização torna-se necessária. OBJETIVO: Examinar se a fluência e seus componentes, agrupamentos (geração sucessiva de palavras pertencentes a uma categoria) e mudança (alternância entre categorias) teriam utilidade na discriminação entre DA, CCL e vcDFT. MÉTODOS: Tarefas de FF (letra P) e FC (animais) foram administradas em inglês a pacientes com CCL (n=25), DA (n=37) e vcDFT (n=17). Escores de agrupamentos e alternância foram calculados através dos critérios estabelecidos. RESULTADOS: Nossos achados sugeriram que 85% dos DA e CCL puderam ser discriminados com sucesso, baseando-se no número total de respostas e alternância na FC. A disparidade FF e FC não foi notada em DA ou vcDFT. O desempenho em agrupamento ou alternância também se provaram insuficientes para discriminar DA de vcDFT. CONCLUSÃO: Alternância foi útil na diferenciação DA de CCL. Em pacientes com DA e vcDFT a progressão das doenças podem levar à atenuação do número total de respostas produzidas em ambas as tarefas de modo que o agrupamento e alternância podem não ser medidas úteis na discriminação destas demências entre si.

Effect of high hydrostatic pressure on Salmonella inoculated into creamy peanut butter with modified composition.

Peanut butter has been associated with several large foodborne salmonellosis outbreaks. This research investigates the potential of high hydrostatic pressure processing (HPP) for inactivation of Salmonella in peanut butter of modified composition, both by modifying its water activity as well by the addition of various amounts of nisin. A cocktail of six Salmonella strains associated with peanut butter and nut-related outbreaks was used for all experiments. Different volumes of sterile distilled water were added to peanut butter to increase water activity, and different volumes of peanut oil were added to decrease water activity. Inactivation in 12% fat, light roast, partially defatted peanut flour, and peanut oil was also quantified. Nisaplin was incorporated into peanut butter at four concentrations corresponding to 2.5, 5.0, 12.5, and 25.0 ppm of pure nisin. All samples were subjected to 600 MPa for 18 min. A steady and statistically significant increase in log reduction was seen as added moisture was increased from 50 to 90%. The color of all peanut butter samples containing added moisture contents darkened after high pressure processing. The addition of peanut oil to further lower the water activity of peanut butter further reduced the effectiveness of HPP. Just over a 1-log reduction was obtained in peanut flour, while inactivation to below detection limits (2 log CFU/g) was observed in peanut oil. Nisin alone without HPP had no effect. Recovery of Salmonella after a combined nisin and HPP treatment did show increased log reduction with longer storage times. The maximum log reduction of Salmonella achieved was 1.7 log CFU/g, which was comparable to that achieved by noncycling pressure treatment alone. High pressure processing alone or with other formulation modification, including added nisin, is not a suitable technology to manage the microbiological safety of Salmonella-contaminated peanut butter.

Effect of high hydrostatic pressure and pressure cycling on a pathogenic Salmonella enterica serovar cocktail inoculated into creamy peanut butter.

The ability of Salmonella enterica serovars to survive in high fat content, low water activity foods like peanut butter has been demonstrated by large foodborne illness outbreaks in recent years. This study investigates the potential of high hydrostatic pressure processing, including pressure cycling, to inactivate Salmonella inoculated into creamy peanut butter. A cocktail of pathogenic strains of Salmonella Enteritidis PT30, Salmonella Tennessee, Salmonella Oranienburg, Salmonella Anatum, Salmonella Enteritidis PT 9c, and Salmonella Montevideo obtained from peanut butter- and nut-related outbreaks was inoculated (10(6) to 10(7) CFU/g) into creamy peanut butter and high pressure processed under five different sets of conditions, which varied from 400 to 600 MPa and from 4 to 18 min. The log CFU reductions achieved varied from 1.6 to 1.9. Control experiments in which Salmonella was inoculated (10(9) CFU/g) into 0.1% peptone buffer and high pressure processed at 600 MPa for 18 min showed inactivation to below the detection limit of 100 CFU/g, confirming that high pressure processing is effective at destroying Salmonella in high-moisture environments. Pressure cycling under three sets of conditions consisting of pressures from 400 to 600 MPa, 3 to 10 pressure cycles, and hold times of 6 min for each cycle showed reductions similar to those seen in noncycling experiments. The results of our experiments suggest that the peanut butter food matrix facilitates the survival of Salmonella when exposed to high hydrostatic pressure processing.