Evaluation of two soybean soapstocks in egg production and quality in Bovans hens

En la alimentación de gallinas en postura se utiliza el aceite crudo de soya (ACS), pero debido a que éste compite con la alimentación humana su precio es alto, por lo cual se evaluaron dos aceites acidulados de soya (AAS), los cuales son más económicos. El objetivo del estudio fue evaluar el efecto de los AAS en la producción de gallinas Bovans, calidad de huevo, composición lipídica y costo de un kilo de huevo. Se determinó la energía metabolizable (EM) y composición de lípidos de los acidulados. Se utilizaron 240 gallinas en seis tratamientos, con cinco repeticiones, con ocho gallinas cada una. En las dietas se incluyeron ACS y dos acidulados (AAST y AASY), a dos niveles (2% y 4%). Las variables productivas fueron alimento consumido, porcentaje de postura, peso del huevo, masa del huevo, conversión alimenticia; en calidad de huevo se midió altura de albumina, unidades Haugh (UH), color de yema y grosor de cascarón. Se determinó la composición lipídica del huevo y su costo. Al sustituir el ACS por los AAS no se afectó la producción de las aves (P>0.05). En calidad de huevo, los AAS mejoraron las UH (P0.05), but did improve Haugh unit values (P<0.05). Egg fatty acids composition changed in response to oil composition (P<0.05), and inclusion concentration affected the levels of specific fatty acids. Use of the soapstocks resulted in a lower cost per kilogram of eggs than with CSO (P<0.05). Substitution of crude soy oil with the evaluated soapstocks had no effect on productive variables, improved egg quality and lowered overall feed costs

Ptpn1 deletion protects oval vells against lipoapotosis by favoring lipid droplet formation and dynamics

Trabajo presentado en el The international liver congress, celebrado en Londres (Inglaterra) del 22 al 26 de junio de 2022.[Background and aims]: Activation of oval cells has been related to hepatocyte injury during chronic liver diseases including nonalcoholic fatty liver disease (NAFLD). However, oval cells plasticity can be affected by the pathological environment. We previously found a protection against hepatocyte cell death by inhibiting protein tyrosine phosphatase 1B (PTP1B). Herein, we investigated the molecular and cellular processes involved in the lipotoxic susceptibility in oval cells expressing or not PTP1B. [Method]: Palmitic acid (PA) induced apoptotic cell death in wild-type (Ptpn1+/+) oval cells in parallel to oxidative stress and impaired autophagy. This lipotoxic effect was attenuated in oval cells lacking Ptpn1 that showed up-regulated antioxidant defences, increased unfolded protein response (UPR) signaling, higher endoplasmic reticulum (ER) content and elevated stearoyl CoA desaturase (Scd1) expression and activity. [Results]: These effects in Ptpn1−/− oval cells concurred with an active autophagy, higher mitochondrial efficiency and a molecular signature of starvation, favoring lipid droplet (LD) formation and dynamics. Autophagy blockade in Ptpn1−/− oval cells reduced Scd1 expression, mitochondrial fitness, LD formation and restored lipoapoptosis, an effect also recapitulated by Scd1 silencing. Importantly, oval cells with LDs were found in livers from Ptpn1−/− mice with NAFLD. [Conclusion]: Ptpn1 deficiency restrained lipoapoptosis in oval cells through a metabolic rewiring towards a “starvation-like” fate, favoring autophagy, mitochondrial fitness and LD formation. Dynamic LD-lysosomal interations likely ensured lipid recycling and, overall, these adaptations protect against lipotoxicity. The identification of LDs in oval cells from Ptpn1−/− mice with NAFLD opens new therapeutic perspectives to ensure oval cells viability and plasticity under lipotoxic liver damage

Changes in the content of chlorophylls and carotenoids in the rind of Fino 49 lemons during maturation and their relationship with parameters from the CIELAB color space

In the present work, the coordinates L*, a* and b* from the CIELAB color space, as well as the chlorophyll, total carotenoids and the content of the carotenoids Lutein and β-cryptoxanthin were measured in the skin of fruits from the Fino 49 lemon during its development, with the aim of understanding the relationship that exists between the color changes of the fruit’s skin (color coordinates) and the pigment content. Also, the understanding of the relative importance of the contents of lutein and β-cryptoxanthin with respect to the total content of carotenoids was sought. The period of study lasted three years; from September 2015 to January 2016, from September 2016 to January 2017, and from September 2017 to January 2018, the periods that comprised the color changes of the lemon fruit until its harvest. The fruits were measured every two weeks in the experimental plot of the IMIDA (Murcian Institute of Agricultural and Food Research and Development) located at La Alberca (Murcia, Spain) and in the experimental orchards from the CEBAS-CSIC, located in Santomera (Murcia). During he experiment, the color and chlorophyll, Lutein and β-cryptoxanthin concentrations were measured. The results showed that there was a good correlation between the color coordinates and the pigments responsible for the lemon’s skin color: all the color pigments were correlated with the a*, b* color coordinates and the Hue angle index. Throughout the fruit’s maturation, a degradation of the chlorophylls was observed, as well as an increase of β-cryptoxanthin, which is responsible for the green and yellow color of the fruits, respectively. Lutein, which was found in high concentrations, decreased with time, but did not contribute to the fruit’s color

Direct medical cost of COVID-19 in children hospitalized at a tertiary referral healthcare center in Mexico City

IntroductionDespite the end of the COVID-19 pandemic being declared by the WHO, the economic consequences are far from over. One of these implications was the cost of inpatient care for health institutions. To date, some studies have examined the economic burden of COVID-19 in the adult population but only a few have focused on child populations.ObjectiveTo estimate the direct medical costs of COVID-19, focusing on children in Mexico.MethodData about resources consumed during hospital stays were extracted from the medical records of patients hospitalized at a Mexican tertiary healthcare institution. Other sources of information were the unit prices of inputs and the salaries of health personnel. A micro-costing methodology was used to obtain cost results by age group over different hospital areas. Data analysis was performed with descriptive statistics and regression models to evaluate the predictors of total cost.ResultsOne hundred and ten medical records were reviewed of which 57.3% corresponded to male patients and the mean age was 7.2 years old. The estimated average cost per patient was US$5,943 (95$4,249–7,637). When the costs of the three clinical areas were summed, only the 5–10 years old group showed a maximum cost of US$14,000. The regression analysis revealed the following factors as significant: sex, age, staying at an emergency room, having a positive bacterial culture, and having comorbidities.DiscussionThe cost results were somewhat similar to those reported in children from the USA, but only regarding low severity COVID-19 cases. However, comparability between these types of studies should be done with caution due to the huge differences between the healthcare systems of countries. The study cost results may help public decision-makers in budget planning and as inputs for future cost-effectiveness studies about interventions regarding COVID-19

Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells

Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against cancer stem cells (CSCs). Hyperpolarization of cell membrane induces cell differentiation and loss of stemness of CSCs leading to effective elimination of this cancer cell subpopulation.panishgovernment and the EU (FIS PI13/00089, FIS PI12/02838,FIS PI12/00956 and RD12/0036/0025), a grant from LaMaratóde TV3 Foundation (20132730), a grant from SEPAR(17/2014), Consejería de Educación de la Junta de Castilla yLeón (Project BU340U13), Ministerio de Economíaycompetitividad/Instituto de Salud Carlos III (SAF2014-55700-P), and ICREA Academia-201

Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

Objective Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. Methods MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice. Results In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice. Conclusions These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1

Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

[Objective]: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. [Methods]: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice. [Results]: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice. [Conclusions]: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.The authors received support for the current study from Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, Spain, MCIN/AEI/10.13039/501100011033 (grants BFU2012-36089 to MJM-A; BFU2015-65937-R to MJM-A, SL-C; PID2019-106982RB-I00 to MJM-A; SAF2017-83813-C3-1-R to LH and PID2021-122766OB-I00 to AMV), cofinanced by the European Regional Development Fund (ERDF); Dept. of Health, Navarra Government (67–2015) to MJM-A; Merck Health Foundation to LH; CIBEROBN (CB12/03/30002; CB06/03/0001; CB06/03/0025) and CIBERDEM (CB07/08/0033) from ISCIII (Spain). “Juan de la Cierva” Grant to MF-G (IJCI-2016-30025) funded by MCIN/AEI/10.13039/501100011033. Predoctoral grant to LML (Asociación de Amigos, Universidad de Navarra/“la Caixa” Banking Foundation) and to LM-F (FPI, BES-2013-064970). S.Q.-V. is supported by a fellowship from the Vicente Lopez Program (Eurecat).Peer reviewe

Lack of EGFR catalytic activity in hepatocytes improves liver regeneration following DDC-induced cholestatic injury by promoting a pro-restorative inflammatory response

Despite the well-known hepatoprotective role of the epidermal growth factor receptor (EGFR) pathway upon acute damage, its specific actions during chronic liver disease, particularly cholestatic injury, remain ambiguous and unresolved. Here, we analyzed the consequences of inactivating EGFR signaling in the liver on the regenerative response following cholestatic injury. For that, transgenic mice overexpressing a dominant negative mutant human EGFR lacking tyrosine kinase activity (ΔEGFR) in albumin-positive cells were submitted to liver damage induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), an experimental model resembling human primary sclerosing cholangitis. Our results show an early activation of EGFR after 1–2 days of a DDC-supplemented diet, followed by a signaling switch-off. Furthermore, ΔEGFR mice showed less liver damage and a more efficient regeneration following DDC injury. Analysis of the mechanisms driving this effect revealed an enhanced activation of mitogenic/survival signals, AKT and ERK1/2-MAPKs, and changes in cell turnover consistent with a quicker resolution of damage in response to DDC. These changes were concomitant with profound differences in the profile of intrahepatic immune cells, consisting of a shift in the M1/M2 balance towards M2 polarity, and the Cd4/Cd8 ratio in favor of Cd4 lymphocytes, overall supporting an immune cell switch into a pro-restorative phenotype. Interestingly, ΔEGFR livers also displayed an amplified ductular reaction, with increased expression of EPCAM and an increased number of CK19-positive ductular structures in portal areas, demonstrating an overexpansion of ductular progenitor cells. In summary, our work supports the notion that hepatocyte-specific EGFR activity acts as a key player in the crosstalk between parenchymal and non-parenchymal hepatic cells, promoting the pro-inflammatory response activated during cholestatic injury and therefore contributing to the pathogenesis of cholestatic liver disease. © 2022 The Pathological Society of Great Britain and Ireland.This work was supported by the Ministry of Science,Innovation and Universities (MICIU) and AgenciaEstatal de Investigacion (AEI), Spain (co-funded byFEDER funds/Development Fund–a Way to BuildEurope): RTI2018-099098-B-100 to AS/BH andRTI2018-094052-B-100 to AMV; and the RamonAreces Foundation: 20th National Competition forScientific and Technical Research in Life and MatterScience (2020) to IF. NL and JGS were recipients ofresearch assistant contracts linked to grant SAF2015-69145-R and RTI2018-099098-B-100, respectively. CMR was the recipient of a researchcontract (PEJD-2019-POST/BMD-16090) from the Education, Universities, Research and Spokesperson Counseling of the Community of Madrid

A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin

Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.This study was funded by the Spanish Group for Research on Sarcoma (GEIS) and partially by PharmaMar. The authors would like to thank the GEIS data center for data management. The authors also thank the donors and the Hospital Universitario Virgen del Rocío—Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041) for part of the human specimens used in this study. David S. Moura is recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155)

MIC of amoxicillin/clavulanate according to CLSI and EUCAST: discrepancies and clinical impact in patients with bloodstream infections due to Enterobacteriaceae

[Objectives] To compare results of amoxicillin/clavulanate susceptibility testing using CLSI and EUCAST methodologies and to evaluate their impact on outcome in patients with bacteraemia caused by Enterobacteriaceae.[Patients and methods] A prospective observational cohort study was conducted in 13 Spanish hospitals. Patients with bacteraemia due to Enterobacteriaceae who received empirical intravenous amoxicillin/clavulanate treatment for at least 48 h were included. MICs were determined following CLSI and EUCAST recommendations. Outcome variables were: failure at the end of treatment with amoxicillin/clavulanate (FEAMC); failure at day 21; and 30 day mortality. Classification and regression tree (CART) analysis and logistic regression were performed.[Results] Overall, 264 episodes were included; the urinary tract was the most common source (64.7%) and Escherichia coli the most frequent pathogen (76.5%). Fifty-two isolates (19.7%) showed resistance according to CLSI and 141 (53.4%) according to EUCAST. The kappa index for the concordance between the results of both committees was only 0.24. EUCAST-derived, but not CLSI-derived, MICs were associated with failure when considered as continuous variables. CART analysis suggested a ‘resistance’ breakpoint of > 8/4 mg/L for CLSI-derived MICs; it predicted FEAMC in adjusted analysis (OR = 1.96; 95% CI: 0.98–3.90). Isolates with EUCAST-derived MICs >16/2 mg/L independently predicted FEAMC (OR = 2.10; 95% CI: 1.05–4.21) and failure at day 21 (OR= 3.01; 95% CI: 0.93–9.67). MICs >32/2 mg/L were only predictive of failure among patients with bacteraemia from urinary or biliary tract sources.[Conclusions] CLSI and EUCAST methodologies showed low agreement for determining the MIC of amoxicillin/clavulanate. EUCAST-derived MICs seemed more predictive of failure than CLSI-derived ones. EUCAST-derived MICs >16/2 mg/L were independently associated with therapeutic failure.The study was funded by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain (Fondo de investigación en salud; PI10/02021) co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015).Peer reviewe