Exploration of isoxanthohumol bioconversion from spent hops into 8-prenylnaringenin using resting cells of Eubacterium limosum

Hops is an almost unique source of the potent phytoestrogen 8-prenylnaringenin (8-PN). As hops contain only low levels of 8-PN, synthesis may be more attractive than extraction. A strain of the Gram-positive Eubacterium limosum was isolated previously for 8-PN production from more abundant precursor isoxanthohumol (IX) from hops. In this study, spent hops, an industrial side stream from the beer industry, was identified as interesting source of IX. Yet, hop-derived compounds are well-known antibacterial agents and the traces of a large variety of different compounds in spent hops interfered with growth and IX conversion. Critical factors to finally enable bacterial 8-PN production from spent hops, using a food and feed grade medium, were evaluated in this research. The use of bacterial resting cells and complex medium at a pH of 7.8-8 best fulfilled the requirements for 8-PN production and generated a solid basis for development of an economic process

Impaired Structural Motor Connectome in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease selectively affecting upper and lower motor neurons. Patients with ALS suffer from progressive paralysis and eventually die on average after three years. The underlying neurobiology of upper motor neuron degeneration and its effects on the complex network of the brain are, however, largely unknown. Here, we examined the effects of ALS on the structural brain network topology in 35 patients with ALS and 19 healthy controls. Using diffusion tensor imaging (DTI), the brain network was reconstructed for each individual participant. The connectivity of this reconstructed brain network was compared between patients and controls using complexity theory without - a priori selected - regions of interest. Patients with ALS showed an impaired sub-network of regions with reduced white matter connectivity (p = 0.0108, permutation testing). This impaired sub-network was strongly centered around primary motor regions (bilateral precentral gyrus and right paracentral lobule), including secondary motor regions (bilateral caudal middle frontal gyrus and pallidum) as well as high-order hub regions (right posterior cingulate and precuneus). In addition, we found a significant reduction in overall efficiency (p = 0.0095) and clustering (p = 0.0415). From our findings, we conclude that upper motor neuron degeneration in ALS affects both primary motor connections as well as secondary motor connections, together composing an impaired sub-network. The degenerative process in ALS was found to be widespread, but interlinked and targeted to the motor connectome

Motor Network Degeneration in Amyotrophic Lateral Sclerosis: A Structural and Functional Connectivity Study

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by motor neuron degeneration. How this disease affects the central motor network is largely unknown. Here, we combined for the first time structural and functional imaging measures on the motor network in patients with ALS and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Structural measures included whole brain cortical thickness and diffusion tensor imaging (DTI) of crucial motor tracts. These structural measures were combined with functional connectivity analysis of the motor network based on resting state fMRI. Focal cortical thinning was observed in the primary motor area in patients with ALS compared to controls and was found to correlate with disease progression. DTI revealed reduced FA values in the corpus callosum and in the rostral part of the corticospinal tract. Overall functional organisation of the motor network was unchanged in patients with ALS compared to healthy controls, however the level of functional connectedness was significantly correlated with disease progression rate. Patients with increased connectedness appear to have a more progressive disease course. CONCLUSIONS/SIGNIFICANCE: We demonstrate structural motor network deterioration in ALS with preserved functional connectivity measures. The positive correlation between functional connectedness of the motor network and disease progression rate could suggest spread of disease along functional connections of the motor network

Cost-effectiveness study of early versus late parenteral nutrition in critically ill children (PEPaNIC)

__Background:__ The multicentre randomised controlled PEPaNIC trial showed that withholding parenteral nutrition (PN) during the first week of critical illness in children was clinically superior to providing early PN. This study describes the cost-effectiveness of this new nutritional strategy. __Methods:__ Direct medical costs were calculated with use of a micro-costing approach. We compared the costs of late versus early initiation of PN (n = 673 versus n = 670 pa

Leukocyte telomere length in paediatric critical illness

__Background:__ Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. __Methods:__ Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. __Results:__ Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P < 0.0001)). Adjusted for potential baseline determinants and leukocyte composition, early PN was associated with telomere shortening during PICU stay as compared with late PN (estimate early versus late PN -0.021 T/S-units, 95% CI -0.038; 0.004, P = 0.01). Other independent determinants of telomere length identified in this model were age, gender, baseline telomere length and fraction of neutrophils in the sample from which the DNA was extracted. Telomere shortening with early PN was independent of post-randomisation factors affected by early PN, including longer length of PICU stay, larger amounts of insulin and higher risk of infection. __Conclusions:__ Shorter than normal leukocyte telomeres are present in critically ill children admitted to the PICU. Early initiation of PN further shortened telomeres, an effect that was independent of other determinants. Whether such telomere-shortening predisposes to long-term consequences of paediatric critical illness should be further investigated in a prospective follow-up study

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

La gestión académica en pandemia : adecuaciones, innovaciones y desafíos de la Universidad Nacional de Cuyo

Este libro remite a un contexto especial e inédito que surge a partir de la pandemia de covid-19. Se trata de un contexto de alcance global signado por efectos intensos y perdurables sobre diferentes aspectos de la realidad social, económica y ambiental. En general, estos efectos provocaron, por un lado, situaciones problemáticas nuevas y, por otro lado, agravaron situaciones problemáticas preexistentes que adquirieron mayor visibilidad. En el caso argentino, las restricciones derivadas de la pandemia agudizaron la brecha socioeducativa existente y, al mismo tiempo, exigieron una gestión ágil, dinámica, resolutiva, propositiva y resiliente, especialmente a las instituciones educativas con el objeto de asegurar el derecho a la educación y su calidad. Lógicamente, la provincia de Mendoza y, por tanto, la Universidad Nacional de Cuyo (UNCUYO) no quedaron exentas de los efectos mencionados. Aunque aún no resulta posible identificar con rigor el impacto concreto que ha tenido la pandemia sobre el funcionamiento del sistema educativo provincial, se pueden entrever algunos indicadores que vale la pena atender. Por ejemplo, el egreso en la oferta de educación superior de la uncuyo registró, en 2020, una caída interanual cercana al -18 % 1. Esta oscilación se torna más relevante si se considera que este indicador se mostraba estable a lo largo de los últimos años.Fil: Castañeda, Linda. Universidad de Murcia.Fil: Viñoles Cosentino, Virginia. Universidad de Murcia.Fil: Falcón, Paulo.Fil: Martínez, Ana María.Fil: Meljin Lombard, Mariela Beatriz. Universidad Nacional de Cuyo. Facultad de Artes y Diseño.Fil: Van Den Bosch, Silvia. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias.Fil: Castro, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Aplicadas a la Industria.Fil: Puebla, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Sánchez, Esther Lucía. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: González Gaviola, Miguel. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Tarabelli, María Florencia. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales.Fil: Rüttler, María Elena. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas.Fil: Nalda, Gonzalo. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas.Fil: Castiglia, Mariana. Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales.Fil: Mussuto, Matías M.. Universidad Nacional de Cuyo. Facultad de Derecho.Fil: Griffouliere, María Gabriela. Universidad Nacional de Cuyo. Facultad de Educación.Fil: Verstraete, María Ana. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras.Fil: Echagaray, Patricia. Universidad Nacional de Cuyo. Facultad de Odontología.Fil: Mirasso, Aníbal. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Molina, Fabiana. Universidad Nacional de Cuyo. Instituto Tecnológico Universitario.Fil: Corral, Patricia. Universidad Nacional de Cuyo. Instituto Universitario de Seguridad Pública.Fil: Chrabalowski, Marina. Universidad Nacional de Cuyo.Fil: Barrozo, María Ana. Universidad Nacional de Cuyo.Fil: Zabala, Cecilia. Universidad Nacional de Cuyo. Escuela de Comercio Martín Zapata.Fil: Sauer, Marcelo. Universidad Nacional de Cuyo.Fil: Romero Day, Marcela. Universidad Nacional de Cuyo. Liceo Agrícola y Enológico Domingo F. Sarmiento.Fil: Marlia, Nora. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Departamento de Aplicación Docente.Fil: Zamorano, Cristina. Universidad Nacional de Cuyo. Colegio Universitario Central.Fil: Yapura, Susana. Universidad Nacional de Cuyo. Escuela del Magisterio.Fil: Navarro, María Fernanda. Universidad Nacional de Cuyo.Fil: Bosio, Iris Viviana. Universidad Nacional de Cuyo. EDIUNC.Fil: Degiorgi, Horacio. Universidad Nacional de Cuyo. Sistema Integrado de Documentación.Fil: Bocco, María Susana. Universidad Nacional de Cuyo.Fil: Guayco, Mariana. Universidad Nacional de Cuyo.Fil: Pizzi, Daniel. Universidad Nacional de Cuyo.Fil: Lettelier, Dolores. Universidad Nacional de Cuyo. Secretaría Académica

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Mind the gap: The mismatch between clinical and imaging metrics in ALS

Advanced magnetic resonance imaging (MRI) techniques hold the promise to capture upper motor neuron loss and extramotor brain changes in amyotrophic lateral sclerosis (ALS) and as such deliver biomarkers relevant to diagnosis, prognosis and monitoring disease progression. However, a correlation between imaging parameters and clinical metrics has thus far been inconsistent across studies. We discuss the contributing factors to this clinical-imaging correlation gap as well as its implications for future research