Urolithin A production drives the effects of pomegranate on the gut microbial metabolism of bile acids and cholesterol in mild dyslipidaemic overweight and obese individuals.

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, varies among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitannins (ETs) and ellagic acid (EA) produces urolithins (Uros), yielding three metabotypes with quantitative and qualitative differences based on dissimilar Uro-producing profiles (UM-A, UM-B, and UM-0, i.e., non-producers). Previous animal studies demonstrated that polyphenols impact BAs and cholesterol microbial metabolism, but data on their effects in humans and data regarding the inter-individual variability of these metabolic conversions are scant. We evaluated whether UMs, as distinctive functional gut-microbiome signatures, could determine the potential effect of a pomegranate extract (PE) rich in ET-EA on the metabolism of BAs and cholesterol in mild dyslipidaemic overweight-obese individuals, with possible consequences on host-lipid homeostasis and gut health. At the baseline, UM-B presented the highest levels of faecal total and secondary BAs and coprostanol, suggesting that the lipid absorption capacity and gut cytotoxic risk could be augmented in UM-B. PE intake significantly reduced faecal coprostanol and BA production, especially secondary BAs, and modulated the gut microbiome, reducing the gut cytotoxic risk, especially in UM-B individuals. The lowering of faecal microbial coprostanol and BAs and some BA-metabolising bacteria was quantitatively correlated with Uro concentrations, mainly faecal Uro-A. This suggests that PE consumption could exert cardiovascular and gut protection through Uro-A production as a direct driver of the effects and indirectly by reducing the Coriobacteriaceae family and BA pool, known factors involved in the gut absorption of lipids.

Phase separation modulates the functional amyloid assembly of human CPEB3.

How functional amyloids are regulated to restrict their activity is poorly understood. The cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is an RNA-binding protein that adopts an amyloid state key for memory persistence. Its monomer represses the translation of synaptic target mRNAs while phase separated, whereas its aggregated state acts as a translational activator. Here, we have explored the sequence-driven molecular determinants behind the functional aggregation of human CPEB3 (hCPEB3). We found that the intrinsically disordered region (IDR) of hCPEB3 encodes both an amyloidogenic and a phase separation domain, separated by a poly-A-rich region. The hCPEB3 amyloid core is composed by a hydrophobic region instead of the Q-rich stretch found in the Drosophila orthologue. The hCPEB3 phase separation domain relies on hydrophobic interactions with ionic strength dependence, and its droplet ageing process leads to a liquid-to-solid transition with the formation of a non-fibril-based hydrogel surrounded by starburst droplets. Furthermore, we demonstrate the differential behavior of the protein depending on its environment. Under physiological-like conditions, hCPEB3 can establish additional electrostatic interactions with ions, increasing the stability of its liquid droplets and driving a condensation-based amyloid pathway.

Unveiling metabotype clustering in resveratrol, daidzein, and ellagic acid metabolism: Prevalence, associated gut microbiomes, and their distinctive microbial networks.

The gut microbiota (GM) produces different polyphenol-derived metabolites, yielding high interindividual variability and hampering consistent health effects. GM metabotypes associated with ellagic acid (urolithin metabotypes A (UMA), B (UMB), and 0 (UM0)), resveratrol (lunularin -producers (LP) and non-producers (LNP)), and daidzein (equol-producers (EP) and non-producers (ENP)) are known. However, individual polyphenol-related metabotypes do not occur individually. In contrast, different combinations coexist (i.e., metabotype clusters, MCs). We report here for the first time these MCs, their distribution, and their associated GM in adult humans (n = 127) after consuming for 7 days a nutraceutical (pomegranate, Polygonum cuspidatum, and red clover extracts) containing ellagitannins + ellagic acid, resveratrol, and isoflavones. Urine metabolites (UHPLC-QTOF-MS) and fecal microbiota (16S rRNA sequencing) were analyzed. Ten MCs were identified: LP + UMB + ENP (22.7%), LP + UMA + ENP (21.3%), LP + UMA + EP (16.7%), LP + UMB + EP (16%), LNP + UMA + ENP (11.3%), LNP + UMB + ENP (5.3%), LNP + UMA + EP (3.3%), LNP + UMB + EP (2%), LNP + UM0 + EP (0.7%), and LNP + UM0 + ENP (0.7%). Sex, BMI, and age did not affect the distribution of metabotypes or MCs. Multivariate analysis (MaAslin2) revealed genera differentially present in individual metabotypes and MCs. Network analysis (MENA) showed the taxa acting as module hubs and connectors. Compositional and functional profiling, alpha and beta diversities, topological network features, and GM modulation by the nutraceutical differed depending on whether the entire cohort or each MC was considered. The nutraceutical did not change the composition of LP + UMA + EP (the most robust GM with the most associated functions) but increased its network connectors. This pioneering approach, joining GM's compositional, functional, and network features in polyphenol metabolism, paves the way for identifying personalized GM-targeted strategies to improve polyphenol health benefits.

A byproduct from the Valles Calchaquíes vineyards (Argentina) rich in phenolic compounds: a tool against endemic Leishmania dissemination.

Vineyard-derived pomace is a byproduct of the wine industry that can have a negative impact on the environment if it is only disposed of or used as a fertilizer. Owing to its polyphenol content, grape pomace is an alternative to biocontrol undesirable microorganisms. In the present study, we characterized the phenolic composition of red and white grape pomace from Valles Calchaquíes, Argentina, and explored its activity against Leishmania (Leishmania) amazonensis, an etiological agent of American tegumentary leishmaniasis, a neglected endemic disease in northern Argentina. Red and white pomace extracts similarly reduced Leishmania viability after a 48-h treatment, with the fractions containing a higher proportion of phenolic compounds being more active. Both extracts stimulated ATPase activity on the parasite plasma membranes, with white grape pomace having a stronger effect than red grape pomace. In addition, the extracts displayed fairly good anticholinesterase activity, which may have contributed to their anti-Leishmania activity. These results reinforce the potential applicability of grape pomace as an antimicrobial agent for the development of biopesticides.

Effects of inorganic and compost tea fertilizers application on the taxonomic and functional microbial diversity of the purslane rhizosphere.

Introduction: Soil fertility is a major determinant of plant-microbial interactions, thus, directly and indirectly affecting crop productivity and ecosystem functions. In this study, we analysed for the first time the effects of fertilizer addition on the cropping of purslane (Portulaca oleracea) with particular attention to the taxonomic and functional characteristics of their associated soil microbiota. Methods: We tested the effects of different doses of inorganic fertilization differing in the amount of N:P:K namely IT1 (300:100:100); IT2 (300:200:100); IT3 (300:200:200); and IT4 (600:100:100) (ppm N:P:K ratio) and organic fertilization (compost tea) which reached at the end of the assay the dose of 300 ppm N. Results and discussion: Purslane growth and soil quality parameters and their microbial community structure, abundance of fungal functional groups and prevailing bacterial metabolic functions were monitored. The application of compost tea and inorganic fertilizers significantly increased the purslane shoot biomass, and some soil chemical properties such as pH and soil enzymatic activities related to C, N and P biogeochemical cycles. The bacterial and fungal community compositions were significantly affected by the organic and chemical fertilizers input. The majority of inorganic fertilization treatments decreased the fungal and bacterial diversity as well as some predictive bacterial functional pathways. Conclusions: These findings suggest that the inorganic fertilization might lead to a change of microbial functioning. However, in order to get stronger evidence that supports the found pattern, longer time-frame experiments that ideally include sampling across different seasons are needed. Thus, further research is still needed to investigate the effects of fertilizations on purslane productivity under commercial field conditions.

[Evolución de marcadores de laboratorio en pacientes con detección persistente de SARS-CoV-2.] / Laboratory markers evolution in patients with persistent detection of SARS-CoV-2.

OBJECTIVE: The study of the evolution of certain biomarkers in patients with persistent detection of SARS-CoV-2 could determine the profile of the pathology that these patients may suffer. The objective of this study was to describe the evolution of different laboratory markers in patients with persistent detection of SARS-CoV-2, and determining these parameters were into reference values. METHODS: Patients were divided into two groups: the control group (G0) included patients with a positive direct test for SARS-CoV-2 followed by 2 negative, while the problem group (G1) included patients with at least 3 consecutive positive tests. The time between consecutive samples was five to twenty days, and only patients with negative serology were included. Demographic data, comorbidities, symptoms, radiology and hospitalization were collected, as well as data from analytic and blood gases. The comparison between the study groups was realized using the t-student and U Mann-Whitney test for quantitative variables, and the χ2 test for qualitative variables. Results with p<0.05 were taken as significant. RESULTS: Ninety patients were included, thirty-eight in G0 and fifty-two in G1. D-dimer decreased 10.20 times more in G0 patients, and normal levels of this parameter at t1 were 1.46 times more frequent in these patients. The percentage of lymphocytes increased sixteen times more in G0, and the normal values in t1 were 10.40 times more common in these patients. C-reactive protein decreased significantly in both groups, and lactate increased more in G1 patients. CONCLUSIONS: The results of the study suggest that some biomarkers evolve differently in patients with persistent detection of SARS-CoV-2, which may have significant clinical impact. This information could help to determine the main organs or systems affected, allowing to anticipate socio-sanitary measures to prevent or compensate these alterations.

OBJETIVO: El estudio de la evolución de algunos biomarcadores en pacientes con detección persistente de SARS-CoV-2 permitiría determinar el perfil de las patologías que podrían padecer. El objetivo de este estudio fue describir la evolución de distintos marcadores de laboratorio en pacientes con detección persistente de SARS-CoV-2 y estudiar los cambios en la proporción de pacientes con valores considerados como normales. METODOS: Los pacientes se dividieron en dos grupos: el grupo control (G0) incluyó pacientes con una prueba de detección de infección activa positiva para SARS-CoV-2 seguida de dos negativas, mientras que el grupo problema (G1) incluyó pacientes con al menos tres pruebas positivas consecutivas. El tiempo entre muestras consecutivas fue de cinco a veinte días, y se incluyeron solamente pacientes con serología negativa. Se recogieron datos demográficos, comorbilidades, sintomatología, radiología y hospitalización, así como los datos de las analíticas y las gasometrías. La comparación entre los grupos de estudio se realizó mediante el test t-student y U Mann-Whitney para variables cuantitativas, y el test de χ2 para variables cualitativas. Se tomaron como significativos resultados con p<0,05. RESULTADOS: Se incluyeron noventa pacientes, treinta y ocho en G0 y cincuenta y dos en G1. El dímero D descendió 10,20 veces más en pacientes G0, y los niveles normales de este parámetro en t1 fueron 1,46 veces más frecuentes en estos pacientes. El porcentaje de linfocitos se elevó dieciséis veces más en G0, y los valores normales en t1 fueron 10,40 veces más habituales en estos pacientes. La proteína C reactiva descendió de manera importante en ambos grupos, y el lactato aumentó más en pacientes G1. CONCLUSIONES: Los resultados del estudio sugieren que algunos biomarcadores evolucionan de manera diferente en pacientes con detección persistente de SARS-CoV-2, lo que podría tener importantes repercusiones clínicas. Esta información podría ayudar a determinar los principales órganos o sistemas afectados, permitiendo anticipar medidas sociosanitarias para prevenir o compensar estas alteraciones.

Evolución de marcadores de laboratorio en pacientes con detección persistente de SARS-CoV-2 / Laboratory markers evolution in patients with persistent detection of SARS-CoV-2

Fundamentos: El estudio de la evolución de algunos biomarcadores en pacientes con detección persistente de SARS-CoV-2permitiría determinar el perfil de las patologías que podrían padecer. El objetivo de este estudio fue describir la evolución de distintosmarcadores de laboratorio en pacientes con detección persistente de SARS-CoV-2 y estudiar los cambios en la proporción de pacien-tes con valores considerados como normales.Métodos: Los pacientes se dividieron en dos grupos: el grupo control (G0) incluyó pacientes con una prueba de detección de infec-ción activa positiva para SARS-CoV-2 seguida de dos negativas, mientras que el grupo problema (G1) incluyó pacientes con al menos trespruebas positivas consecutivas. El tiempo entre muestras consecutivas fue de cinco a veinte días, y se incluyeron solamente pacientescon serología negativa. Se recogieron datos demográficos, comorbilidades, sintomatología, radiología y hospitalización, así como los da-tos de las analíticas y las gasometrías. La comparación entre los grupos de estudio se realizó mediante el test t-student y U Mann-Whitneypara variables cuantitativas, y el test de χ2 para variables cualitativas. Se tomaron como significativos resultados con p<0,05. Resultados: Se incluyeron noventa pacientes, treinta y ocho en G0 y cincuenta y dos en G1. El dímero D descendió 10,20 vecesmás en pacientes G0, y los niveles normales de este parámetro en t1 fueron 1,46 veces más frecuentes en estos pacientes. El porcenta-je de linfocitos se elevó dieciséis veces más en G0, y los valores normales en t1 fueron 10,40 veces más habituales en estos pacientes.La proteína C reactiva descendió de manera importante en ambos grupos, y el lactato aumentó más en pacientes G1.Conclusiones: Los resultados del estudio sugieren que algunos biomarcadores evolucionan de manera diferente en pacientes...(AU)

B:ackground: The study of the evolution of certain biomarkers in patients with persistent detection of SARS-CoV-2 could determinethe profile of the pathology that these patients may suffer. The objective of this study was to describe the evolution of different laboratorymarkers in patients with persistent detection of SARS-CoV-2, and determining these parameters were into reference values.Methods: Patients were divided into two groups: the control group (G0) included patients with a positive direct test for SARS-CoV-2followed by 2 negative, while the problem group (G1) included patients with at least 3 consecutive positive tests. The time betweenconsecutive samples was five to twenty days, and only patients with negative serology were included. Demographic data, comorbidities,symptoms, radiology and hospitalization were collected, as well as data from analytic and blood gases. The comparison between thestudy groups was realized using the t-student and U Mann-Whitney test for quantitative variables, and the χ2 test for qualitative variables.Results with p<0.05 were taken as significant.Results: Ninety patients were included, thirty-eight in G0 and fifty-two in G1. D-dimer decreased 10.20 times more in G0 patients,and normal levels of this parameter at t1 were 1.46 times more frequent in these patients. The percentage of lymphocytes increasedsixteen times more in G0, and the normal values in t1 were 10.40 times more common in these patients. C-reactive protein decreasedsignificantly in both groups, and lactate increased more in G1 patients.Conclusions: The results of the study suggest that some biomarkers evolve differently in patients with persistent detectionof SARS-CoV-2, which may have significant clinical impact. This information could help to determine the main organs or systemsaffected, allowing to anticipate socio-sanitary measures to prevent or compensate these alterations.(AU)

In vivo administration of gut bacterial consortia replicates urolithin metabotypes A and B in a non-urolithin-producing rat model.

Urolithin (Uro) production capacity and, consequently, at least partly, the health effects attributed to ellagitannin and ellagic acid consumption vary among individuals. The reason is that not all individuals have the gut bacterial ecology needed to produce the different Uro metabolites. Three human urolithin metabotypes (UM-A, UM-B, and UM-0) based on dissimilar Uro production profiles have been described in populations worldwide. Recently, the gut bacterial consortia involved in ellagic acid metabolism to yield the urolithin-producing metabotypes (UM-A and UM-B) in vitro have been identified. However, the ability of these bacterial consortia to customize urolithin production to mimic UM-A and UM-B in vivo is still unknown. In the present study, two bacterial consortia were assessed for their capacity to colonize the intestine of rats and convert UM-0 (Uro non-producers) animals into Uro-producers that mimic UM-A and UM-B, respectively. Two consortia of Uro-producing bacteria were orally administered to non-urolithin-producing Wistar rats for 4 weeks. Uro-producing bacterial strains effectively colonized the rats' gut, and the ability to produce Uros was also effectively transferred. Bacterial strains were well tolerated. No changes in other gut bacteria, except Streptococcus reduction, or adverse effects on haematological and biochemical parameters were observed. Besides, two novel qPCR procedures were designed and successfully optimized to detect and quantify Ellagibacter and Enterocloster genera in faecal samples. These results suggest that the bacterial consortia are safe and could be potential probiotics for human trials, which is especially relevant for UM-0 individuals, who cannot produce bioactive Uros.

Estudio de casos-controles de la infección por Clostridioides difficile en un área sanitaria rural / Case-control study of Clostridioides difficile in a rural health care area

Objetivo: Determinar los factores de riesgo y factores pronósticos de la infección por Clostridioides difficile (ICD). Pacientes y métodos: Estudio prospectivo de casos-controles (61 casos y 64 controles) de 2 años o más con diarrea, atendidos en un área sanitaria manchega durante 14 meses. El diagnóstico se realizó mediante inmunocromatografía (glutamato deshidrogenasa y toxina A/B), realizando amplificación isotérmica en los casos discordantes. Se recogieron variables demográficas, comorbilidades, tipo de adquisición, administración previa de antibióticos, antiácidos e inmunosupresores y evolución. Los datos se analizaron mediante la prueba de χ2 y el efecto de los factores de riesgo y pronósticos se cuantificó mediante odds ratio con intervalos de confianza del 95%. Resultados: Como factores de riesgo independientes de ICD encontramos el ingreso hospitalario las 4 semanas previas a la infección, la hipoalbuminemia y la administración previa de antibióticos. Presentar estos 3 factores supuso un riesgo casi 3 veces mayor de infectarse. En el grupo de adquisición nosocomial se encontró mayor número de ingresos hospitalarios las 4-12 semanas previas a la ICD y, aunque hubo mayor tendencia a las recurrencias y al pronóstico desfavorable entre los casos intrahospitalarios, estas diferencias no fueron significativas. Identificamos como factores de pronóstico desfavorable la fiebre y el ingreso hospitalario las 4 semanas previas a la infección. Conclusiones:Los factores de riesgo independientes de ICD fueron: ingreso hospitalario las 4 semanas previas a la infección, hipoalbuminemia y administración previa de antibióticos. La fiebre y la hospitalización las 4 semanas anteriores se identificaron además como factores pronósticos de evolución desfavorable.(AU)

Objective: To determine the risk and prognostic factors for Clostridioides difficile infection (CDI). Patients and methods: Prospective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals. Results: Hospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI. Conclusions: The independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution.(AU)

Case-control study of Clostridioides difficile in a rural health care area. / Estudio de casos-controles de la infección por Clostridioides difficile en un área sanitaria rural.

OBJECTIVE: To determine the risk and prognostic factors for Clostridioides difficile infection (CDI). PATIENTS AND METHODS: Prospective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals. RESULTS: Hospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI. CONCLUSIONS: The independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution.

[Potential usefulness of CT as a marker of persistence of positive PCR in patients with COVID-19.] / Potencial utilidad del CT como marcador de persistencia de PCR positiva en pacientes con COVID-19.

OBJECTIVE: One of the problems associated to SARS-CoV-2 was its persistence in nasopharyngeal tract. The existence of markers that help to predict this situation could be useful to management of the patients. The objective of this paper was to determine the relationship between the CT value from the initial PCR of patients with COVID-19 and the persistence of the infection. METHODS: It was performed an observational retrospective study of patients with positive PCR to SARS-CoV-2 attended in emergency department of a general hospital. Data about compatible symptoms, radiological findings and the CT value obtained with each PCR kit were collected. The control group (G0) included patients with a positive PCR followed by two negative PCR results (P-N-N), while problem group (G1) included patients with at least three consecutive positive PCR results (P-P-P). Chronic infections were discarded selecting only patients with negative serology, and only were included those whose PCR were separated by a minimum of five and maximum of twenty days. The comparison between the study groups was carried out using the t-student test for quantitative variables and the χ2 test for qualitative variables. RESULTS: The mean CT value were 30.8 and 21.5 (p<0.001) on G0 and G1, respectively. G0 reported higher CT values than G1, regardless of symptoms, radiological pattern and the PCR kit utilized. CONCLUSIONS: The CT value from the SARS-CoV-2 initial PCR is related to the persistence of its positivity, regardless of the patient´s symptoms or radiological pattern. Thus, low CT values could be related to persistent infections.

OBJETIVO: Uno de los problemas asociados al SARS-CoV-2 es su persistencia en el tracto nasofaríngeo. La existencia de marcadores que ayuden a predecir este fenómeno podría ser útil en el manejo del paciente. El objetivo de este trabajo fue determinar la relación entre el valor CT (umbral de ciclo) de la PCR inicial de pacientes con COVID-19 y la persistencia de la infección. METODOS: Se realizó un estudio observacional retrospectivo de pacientes con PCR positiva para SARS-CoV-2 atendidos en las Urgencias de un hospital general. Se recogieron datos sobre sintomatología compatible y patrón radiológico de cada paciente, así como el CT obtenido en la PCR con cada equipo utilizado. El grupo control (G0) incluyó pacientes con una PCR positiva seguida de dos negativas (patrón P-N-N), mientras que el grupo problema (G1) incluyó pacientes con al menos tres PCR positivas consecutivas (patrón P-P-P). Se descartaron las infecciones crónicas, considerando únicamente a pacientes con serología negativa, y solo se incluyeron aquellos cuyas tres PCR estuvieron separadas un mínimo de cinco días y un máximo de veinte. La comparación entre los grupos de estudio se realizó mediante el test t-student para variables cuantitativas y el test de χ2 para variables cualitativas. RESULTADOS: La media del valor CT fue de 30,8 en G0 y 21,5 en G1 (p<0,001). G0 reportó CT superiores a G1, independientemente de la sintomatología, el patrón radiológico o el equipo de PCR utilizado. CONCLUSIONES: El valor CT de la PCR inicial de SARS-CoV-2 podría relacionase con la persistencia de su positividad, independientemente de la sintomatología o el patrón radiológico del paciente. Valores bajos de CT en la primera PCR podrían relacionarse con infecciones persistentes.

Potencial utilidad del CT como marcador de persistencia de PCR positiva en pacientes con COVID-19 / Potential usefulness of CT as a marker of persistence of positive PCR in patients with COVID-19

FUNDAMENTOS: Uno de los problemas asociados al SARS-CoV-2 es su persistencia en el tracto nasofaríngeo. La existencia de marcadores que ayuden a predecir este fenómeno podría ser útil en el manejo del paciente. El objetivo de este trabajo fue determinar la relación entre el valor CT (umbral de ciclo) de la PCR inicial de pacientes con COVID-19 y la persistencia de la infección. MÉTODOS: Se realizó un estudio observacional retrospectivo de pacientes con PCR positiva para SARS-CoV-2 atendidos en las Urgencias de un hospital general. Se recogieron datos sobre sintomatología compatible y patrón radiológico de cada paciente, así como el CT obtenido en la PCR con cada equipo utilizado. El grupo control (G0) incluyó pacientes con una PCR positiva seguida de dos negativas (patrón P-N-N), mientras que el grupo problema (G1) incluyó pacientes con al menos tres PCR positivas consecutivas (patrón P-P-P). Se descartaron las infecciones crónicas, considerando únicamente a pacientes con serología negativa, y solo se incluyeron aquellos cuyas tres PCR estuvieron separadas un mínimo de cinco días y un máximo de veinte. La comparación entre los grupos de estudio se realizó mediante el test t-student para variables cuantitativas y el test de χ2 para variables cualitativas. RESULTADOS: La media del valor CT fue de 30,8 en G0 y 21,5 en G1 (p<0,001). G0 reportó CT superiores a G1, independientemente de la sintomatología, el patrón radiológico o el equipo de PCR utilizado. CONCLUSIONES: El valor CT de la PCR inicial de SARS-CoV-2 podría relacionase con la persistencia de su positividad, independientemente de la sintomatología o el patrón radiológico del paciente. Valores bajos de CT en la primera PCR podrían relacionarse con infecciones persistentes.(AU)

BACKGROUND: One of the problems associated to SARS-CoV-2 was its persistence in nasopharyngeal tract. The existence of markers that help to predict this situation could be useful to management of the patients. The objective of this paper was to determine the relationship between the CT value from the initial PCR of patients with COVID-19 and the persistence of the infection. METHODS: It was performed an observational retrospective study of patients with positive PCR to SARS-CoV-2 attended in emergency department of a general hospital. Data about compatible symptoms, radiological findings and the CT value obtained with each PCR kit were collected. The control group (G0) included patients with a positive PCR followed by two negative PCR results (P-N-N), while problem group (G1) included patients with at least three consecutive positive PCR results (P-P-P). Chronic infections were discarded selecting only patients with negative serology, and only were included those whose PCR were separated by a minimum of five and maximum of twenty days. The comparison between the study groups was carried out using the t-student test for quantitative variables and the χ2 test for qualitative variables. RESULTS: The mean CT value were 30.8 and 21.5 (p<0.001) on G0 and G1, respectively. G0 reported higher CT values than G1, regardless of symptoms, radiological pattern and the PCR kit utilized.(AU)

Urolithins: potential biomarkers of gut dysbiosis and disease stage in Parkinson's patients.

Gut microbiota alteration (gut dysbiosis) occurs during the onset and progression of Parkinson's disease. Gut dysbiosis biomarkers could be relevant to prodromal disease. Urolithins, anti-inflammatory metabolites produced from some dietary polyphenols by specific gut microbial ecologies (urolithin metabotypes), have been proposed as biomarkers of gut microbiota composition and functionality. However, this has not been explored in Parkinson's disease patients. The current study aimed to assess associations between urolithin metabotypes, gut dysbiosis and disease severity in Parkinson's disease patients. Participants (52 patients and 117 healthy controls) provided stool samples for microbiota sequencing and urine samples for urolithin profiling before and after consuming 30 g of walnuts for three days. Data on demographics, medication, disease duration and Hoehn and Yahr disease stage were collected. We observed a significant gradual increase of urolithin non-producers (metabotype-0) as the disease severity increased. The gut microbiome of metabotype-0 patients and patients with the greatest severity was characterized by a more altered bacterial composition, i.e., increased pro-inflammatory Enterobacteriaceae and reduced protective bacteria against autoimmune and inflammatory processes, including butyrate and urolithin-producing bacteria (Lachnospiraceae members and Gordonibacter). Besides, their microbiome was characterized by predictive functions of lipopolysaccharide biosynthesis and metabolism of glutathione, cysteine and methionine that could indirectly reflect the gut pro-inflammatory status. Urolithin detection in urine is a feasible, non-invasive and fast approach that can reflect gut microbiome dysbiosis and intestinal inflammation in Parkinson's disease patients. Our current study could provide novel strategies for improving diagnostics, and for preventing and treating disease progression in microbiota-based interventions.

Diseminación interhospitalaria de Klebsiella pneumoniae ST512 productora de KPC-3. Detección por MALDI-TOF / Interhospital dissemination of KPC-3 producing-Klebsiella pneumoniae ST512. Detection by MALDI-TOF

Introducción/Objetivo: Describir un brote por Klebsiella pneumoniae (KPN) productora de KPC-3 y determinar la eficacia diagnóstica de MALDI-TOF en su detección. Métodos: Estudio retrospectivo de las KPN-KPC-3 aisladas en 2 hospitales de Ciudad Real. Se buscó el pico a 11,109kDa±15 en el espectro proporcionado por MALDI-TOF para KPN. Resultados: Se aislaron 156 cepas de KPN que portaban el gen blaKPC-3, con un único perfil perteneciente al ST512 (31 cepas estudiadas). Hubo un 25% de infectados. Un 84% tuvieron origen nosocomial o relacionado con la asistencia sanitaria. El 93% tenía alguna enfermedad de base (31% de exitus en el primer mes). La detección del pico mostró una sensibilidad del 90% y una especificidad del 100%. Conclusiones: Detectamos la diseminación clonal de una cepa de KPN ST512 productora de KPC-3 en 3 hospitales de Ciudad Real. Además, evidenciamos la rentabilidad de MALDI-TOF en la detección precoz de KPN-KPC.(AU)

Introduction/Objective: To describe an outbreak of KPC-3-producing Klebsiella pneumoniae (KPN) and determine the diagnostic efficacy of MALDI-TOF in its detection. Methods: Retrospective study of the KPC-3-KPN isolated in 2 hospitals in Ciudad Real. The peak at 11,109kDa±15 was sought in the KPN spectra provided by MALDI-TOF. Results: We isolated 156 KPN strains that carried the blaKPC-3 gene, with a unique profile belonging to ST512 (31 strains studied). There was 25% of infected patients, 84% were nosocomial or related to health care and 93% had some underlying disease (31% of exitus in the first month). The detection of the peak showed 90% sensitivity and 100% specificity. Conclusions: We detected the clonal spread of a KPN ST512 strain producing KPC-3 in 3 hospitals in Ciudad Real. In addition, we show the profitability of MALDI-TOF in the early detection of KPC-KPN.

Clinical Characteristics, Frailty, and Mortality of Residents With COVID-19 in Nursing Homes of a Region of Madrid.

OBJECTIVES: To describe the clinical characteristics, 30-day mortality, and associated factors of patients living in nursing homes (NH) with COVID-19, from March 20 to June 1, 2020. DESIGN: This is a retrospective study. A geriatric hospital-based team acted as a consultant and coordinated the care of older people living in NHs from the hospital. SETTING AND PARTICIPANTS: A total of 630 patients aged 70 and older with Coronavirus Disease 2019 COVID-19 living in 55 NHs. METHODS: A logistic regression was performed to analyze the factors associated with mortality. In addition, Kaplan-Meier curves were applied according to mortality and its associated factors using the log-rank Mantel-Cox test. RESULTS: The diagnosis of COVID-19 was mainly made by clinical compatibility (N = 430). Median age was 87 years, 64.6% were women and 45.9% were transferred to be cared for at the hospital. A total of 282 patients died (44.7%) within the 30 days of first attention by the team. A severe form of COVID-19 occurred in 473 patients, and the most frequent symptoms were dyspnea (n = 332) and altered level of consciousness (n = 301). According to multiple logistic regression, male sex (P = .019), the Clinical Frailty Score (CFS) ≥6 (P = .004), dementia (P = .012), dyspnea (P < .001), and having a severe form of COVID-19 (P = .001), were associated with mortality, whereas age and care setting were not. CONCLUSIONS AND IMPLICATIONS: Mortality of the residents living in NHs with COVID-19 was almost 45%. The altered level of consciousness as an atypical presentation of COVID-19 should be considered in this population. A severe form of the disease, present in more than three-quarters of patients, was associated with mortality, apart from the male sex, CFS ≥6, dementia, and dyspnea, whereas age and care setting were not. These findings may also help to recognize patients in which the Advance Care Planning process is especially urgent to assist in the decisions about their care.

Interhospital dissemination of KPC-3 producing-Klebsiella pneumoniae ST512. Detection by MALDI-TOF. / Diseminación interhospitalaria de Klebsiella pneumoniae ST512 productora de KPC-3. Detección por MALDI-TOF.

INTRODUCTION/OBJECTIVE: To describe an outbreak of KPC-3-producing Klebsiella pneumoniae (KPN) and determine the diagnostic efficacy of MALDI-TOF in its detection. METHODS: Retrospective study of the KPC-3-KPN isolated in 2 hospitals in Ciudad Real. The peak at 11,109kDa±15 was sought in the KPN spectra provided by MALDI-TOF. RESULTS: We isolated 156 KPN strains that carried the blaKPC-3 gene, with a unique profile belonging to ST512 (31 strains studied). There was 25% of infected patients, 84% were nosocomial or related to health care and 93% had some underlying disease (31% of exitus in the first month). The detection of the peak showed 90% sensitivity and 100% specificity. CONCLUSIONS: We detected the clonal spread of a KPN ST512 strain producing KPC-3 in 3 hospitals in Ciudad Real. In addition, we show the profitability of MALDI-TOF in the early detection of KPC-KPN.

Inactivation of Listeria monocytogenes and Salmonella Typhimurium in strawberry juice enriched with strawberry polyphenols.

BACKGROUND: Low molecular-weight phenolic fractions (LMPFs) were extracted from Albion (LMPF-A) and Camarosa (LMPF-C) strawberry cultivars. Their antibacterial activity against Listeria monocytogenes and Salmonella Typhimurium cocktails in vitro and in vivo was investigated using strawberry juice as a food model. This study also sought to determine their antibacterial mechanism. RESULTS: Quercetin was identified as a principal compound in both phenolic fractions. The minimum bactericide concentration (MBC) values were 750 and 850 µg mL-1 (LMPF-C) and 800 and 950 µg mL-1 (LMPF-A) against S.Typhimurium and L. monocytogenes, respectively. The possible antibacterial activity of the phenolic extracts could be related to the release of phosphate and potassium ions, the effect of the disruption of membrane integrity on L. monocytogenes, and the effect of the inhibition of dihydronicotinamide adenine dinucleotide (NADH) oxidase activity on S. Typhimurium. Quercetin and kaempferol were the most active compounds in producing bacterial damage. Strawberry juice supplemented with the phenolic fractions and incubated at 37, 20, and 4 °C reduced bacterial viability; moreover, after treatment with the phenolic fraction at the lowest temperature, no viable cells were detected after 7 days' incubation. Salmonella was more sensitive to the supplements than Listeria in strawberry juice. CONCLUSIONS: This study could form the basis for the development of natural antibacterial agents that could be included in natural juice or used by the pharmaceutical industry. © 2020 Society of Chemical Industry.