Applicability of Clinical Decision Support in Management among Patients Undergoing Cardiac Surgery in Intensive Care Unit: A Systematic Review

[Abstract] The advances achieved in recent decades regarding cardiac surgery have led to a new risk that goes beyond surgeons’ dexterity; postoperative hours are crucial for cardiac surgery patients and are usually spent in intensive care units (ICUs), where the patients need to be continuously monitored to adjust their treatment. Clinical decision support systems (CDSSs) have been developed to take this real-time information and provide clinical suggestions to physicians in order to reduce medical errors and to improve patient recovery. In this review, an initial total of 499 papers were considered after identification using PubMed, Web of Science, and CINAHL. Twenty-two studies were included after filtering, which included the deletion of duplications and the exclusion of titles or abstracts that were not of real interest. A review of these papers concluded the applicability and advances that CDSSs offer for both doctors and patients. Better prognosis and recovery rates are achieved by using this technology, which has also received high acceptance among most physicians. However, despite the evidence that well-designed CDSSs are effective, they still need to be refined to offer the best assistance possible, which may still take time, despite the promising models that have already been applied in real ICUs.Xunta de Galicia; ED431C 2018/4

Analysis of a Real-World Cohort of Metastatic Breast Cancer Patients Shows Circulating Tumor Cell Clusters (CTC-clusters) as Predictors of Patient Outcomes

Circulating tumor cell (CTC) enumeration has emerged as a powerful biomarker for the assessment of prognosis and the response to treatment in metastatic breast cancer (MBC). Moreover, clinical evidences show that CTC-cluster counts add prognostic information to CTC enumeration, however, their significance is not well understood, and more clinical evidences are needed. We aim to evaluate the prognostic value of longitudinally collected single CTCs and CTC-clusters in a heterogeneous real-world cohort of 54 MBC patients. Blood samples were longitudinally collected at baseline and follow up. CTC and CTC-cluster enumeration was performed using the CellSearch® system. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using Cox proportional hazards modelling. Elevated CTC counts and CTC-clusters at baseline were significantly associated with a shorter survival time. In joint analysis, patients with high CTC counts and CTC-cluster at baseline were at a higher risk of progression and death, and longitudinal analysis showed that patients with CTC-clusters had significantly shorter survival compared to patients without clusters. Moreover, patients with CTC-cluster of a larger size were at a higher risk of death. A longitudinal analysis of a real-world cohort of MBC patients indicates that CTC-clusters analysis provides additional prognostic value to single CTC enumeration, and that CTC-cluster size correlates with patient outcomeThis research was supported by Roche-Chus Joint Unit (IN853B 2018/03), funded by Axencia Galega de Innovación (GAIN), Consellería de Economía, Emprego e Industria and by the Instituto de Salud Carlos III (ISCIII) and FEDER (PI13/01388). L.M.-R. is supported by Asociación Española Contra el Cáncer (AECC). I.M.-P. is funded by the Training Program for Academic Staff fellowship (FPU16/01018), from the Ministry of Education and Vocational Training, Spanish GovernmentS

Especies de Paracoccidioides circulantes en Paraguay y su relación con características epidemiológicas y clínicas de los pacientes.

El objetivo general del proyecto fue identificar especies de Paracoccidioides circulantes en Paraguay y relacionar con las características epidemiológicas y clínicas de los pacientes.CONACYT - Consejo Nacional de Ciencias y TecnologíaPROCIENCI

Serum-Metaboliten-Konzentrationen und Enzymaktivitäten in mit verschiedenen Futtermittelarten mit hohem Getreideanteil gefütterten Mastbullenkälbern

Between the ages of 23 and 35 weeks, various serum metabolites and enzymes were monitored in three 10-animal groups of double-muscled Belgian Blue bull calves maintained in a feedlot in Galicia (NW Spain) on high-grain finishing diets that mainly differed in whether the grain used was predominantly maize (group M), predominantly barley (group B), or a mixture of maize and barley in approximately equal proportions (group MB). The parameters determined were glucose, non-esterified fatty acids (NEFA), total serum protein concentration (TSP), albumin, serum urea nitrogen (SUN), creatinine, aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). Throughout the study period, all these parameters remained within the physiological ranges for beef under intensive conditions, and no animal ever showed clinical symptoms of ruminal alterations; indicating that none of these highgrain diets were detrimental to animal health. Although average serum NEFA, creatinine, albumin, AST and GGT levels all differed among groups, only AST can be considered as possible age-independent marker of grain-type-related metabolic alterations, since the other parameters all showed significant time×group interaction. In terms of this parameter, animals fed a MB diet behaved similarly to those fed a B diet. The absence of between-group differences in blood glucose level may reflect a genetic characteristic of this double-muscled breed. Our results, in conjunction with the best productive results obtained in animals fed de B-diet, aim us to suggest that the risk of an acidogenic diet would depend strongly on the nutritional management (in terms of crude protein (CP) and quality of straw in the ration) and not only the type of grain.Zwischen dem Alter von 23 und 35 Wochen wurde ein Monitoring durchgeführt der verschiedenen Serum-Metaboliten und Enzyme mit drei Gruppen zu jeweils 10 Weißblauen Belgier-Bullenkälbern mit starker Muskelfülle, die in einer Mastparzelle in Galizien (NW Spanien) mit Mastfuttermittelarten mit hohem Getreideanteil gehalten wurden, die sich hauptsächlich darin unterschieden, dass das verwendete Getreide überwiegend aus Mais (Gruppe M), überwiegend aus Gerste (Gruppe B) oder aus einem Gemisch von Mais und Gerste zu ungefähr gleichen Teilen (Gruppe MB) bestand. Die nachgewiesenen Parameter waren Glukose, nicht veresterte Fettsäuren (NEFA), Serum-Gesamtproteinkonzentration (TSP), Albumin, Serum-Harnstoffstickstoff (SUN), Creatinin, Aspartataminotransferase (ASTZ) und γ-Glutamyltransferase (GGT). Während des Untersuchungszeitraums blieben diese Parameter durchwegs innerhalb des für Rindfleisch unter intensiven Haltungsbedingungen physiologischen Bereichs, und kein Tier zeigte zu irgendeiner Zeit klinische Symptome einer Rumen-Veränderung, so dass keines dieser Futtermittel mit hohem Getreideanteil der tierischen Gesundheit abträglich war. Obwohl die durchschnittlichen Konzentrationen von NEFA, Creatinin, Albumin, AST und GGT im Serum in den Gruppen alle unterschiedlich waren, kann nur AST als möglicher altersunabhängiger Marker von getreidebedingten Stoffwechselveränderungen betrachtet werden, da die anderen Parameter alle eine signifikante Wechselwirkung zwischen Zeit und Gruppe zeigten. Im Hinblick auf diese Parameter verhielten sich Tiere, an die ein MB-Futtermittel verfüttert wurde, wie diejenigen, an die ein B-Futtermittel verfüttert wurde. Das Fehlen von Intergruppenunterschieden hinsichtlich des Blut-Glukosespiegels könnte ein genetisches Merkmal dieser Rasse mit starker Muskelfülle widerspiegeln. Unsere Ergebnisse, zusammen mit den besten, mit Tieren, denen das B-Futter verfüttert wurde, erhaltenen Nutzergebnissen veranlassen uns zu dem Vorschlag, dass das Risiko einer azidogenen Fütterung stark vom Fütterungsmanagement (hinsichtlich Roheiweiß (CP) und Qualitätsstroh in der Ration) und nicht nur vom Getreidetyp abhängt.This work was supported by the Xunta de Galicia (Spain) through grant XUGA 2002/CG320S

Modulation of hypothalamic AMPK phosphorylation by olanzapine controls energy balance and body weight

[Background]: Second-generation antipsychotics (SGAs) are a mainstay therapy for schizophrenia. SGA-treated patients present higher risk for weight gain, dyslipidemia and hyperglycemia. Herein, we evaluated the effects of olanzapine (OLA), widely prescribed SGA, in mice focusing on changes in body weight and energy balance. We further explored OLA effects in protein tyrosine phosphatase-1B deficient (PTP1B-KO) mice, a preclinical model of leptin hypersensitivity protected against obesity.[Methods]: Wild-type (WT) and PTP1B-KO mice were fed an OLA-supplemented diet (5 mg/kg/day, 7 months) or treated with OLA via intraperitoneal (i.p.) injection or by oral gavage (10 mg/kg/day, 8 weeks). Readouts of the crosstalk between hypothalamus and brown or subcutaneous white adipose tissue (BAT and iWAT, respectively) were assessed. The effects of intrahypothalamic administration of OLA with adenoviruses expressing constitutive active AMPKα1 in mice were also analyzed.[Results]: Both WT and PTP1B-KO mice receiving OLA-supplemented diet presented hyperphagia, but weight gain was enhanced only in WT mice. Unexpectedly, all mice receiving OLA via i.p. lost weight without changes in food intake, but with increased energy expenditure (EE). In these mice, reduced hypothalamic AMPK phosphorylation concurred with elevations in UCP-1 and temperature in BAT. These effects were also found by intrahypothalamic OLA injection and were abolished by constitutive activation of AMPK in the hypothalamus. Additionally, OLA i.p. treatment was associated with enhanced Tyrosine Hydroxylase (TH)-positive innervation and less sympathetic neuron-associated macrophages in iWAT. Both central and i.p. OLA injections increased UCP-1 and TH in iWAT, an effect also prevented by hypothalamic AMPK activation. By contrast, in mice fed an OLA-supplemented diet, BAT thermogenesis was only enhanced in those lacking PTP1B. Our results shed light for the first time that a threshold of OLA levels reaching the hypothalamus is required to activate the hypothalamus BAT/iWAT axis and, therefore, avoid weight gain.[Conclusion]: Our results have unraveled an unexpected metabolic rewiring controlled by hypothalamic AMPK that avoids weight gain in male mice treated i.p. with OLA by activating BAT thermogenesis and iWAT browning and a potential benefit of PTP1B inhibition against OLA-induced weight gain upon oral treatment.This work was funded by grants PID-2021-122766OB-100 (to AMV) and PID2019-104399RB-I00 (to GS) funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación /10.13039/501100011033 and “ERDF A way of making Europe” by the European Union. We also acknowledge grants H2020 Marie Sklodowska-Curie ITN-TREATMENT (Grant Agreement 721236, European Commission), S2017/BMD-3684 (Comunidad de Madrid, Spain), Fundación Ramón Areces (Spain) and CIBERdem (ISCIII, Spain) to AMV. JWE was funded by the Swedish Diabetes Foundation and the Novo Nordisk Foundation (NNF20OC0063864). VF was a recipient of a contract from ITN-TREATMENT and is currently a PhD fellow from the Portuguese Foundation for Science and Technology (FCT, Portugal)/ERDF (2020.08388.BD). CF was awarded with Sara Borrell contract (CD19/00078, ISCIII, Spain)

Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons

There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi -> spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.This study was supported by grants cofinanced by the 'Fondo Europeo de Desarrollo Regional' (FEDER)-UE 'A way to build Europe' from the `Ministerio de Economia y Competitividad' (MINECO: RTI2018-099778-B-I00) and by the 'Ministerio de SaludInstituto de Salud Carlos III' (PI18/01691); the 'Consejeria de Salud de la Junta de Andalucia' (PI-0134-2018); the 'Programa Operativo de Andalucia FEDER, Iniciativa Territorial Integrada ITI 2014-2020 Consejeria Salud, Junta de Andalucia' (PI-0080-2017); the "Consejeri ' a de Transformacion Economica, Industria, Conocimiento y Universidades, Junta de Andalucia" (PEMP-00082020), Instituto de Investigacion e Innovacion en Ciencias Biomedicas de Cadiz (INiBICA LI19/06IN-CO22); the `Consejeri ' a de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia' (CTS-510); the 'Centro de Investigacion Biomedica en Red de Salud Mental-CIBERSAM' (CB/07/09/0033) and the Academy of Finland (315043)

Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells

Traditionally, studies to address the characterization of mechanisms promoting tumor aggressiveness and progression have been focused only on primary tumor analyses, which could provide relevant information but have limitations to really characterize the more aggressive tumor population. To overcome these limitations, circulating tumor cells (CTCs) represent a noninvasive and valuable tool for real-time profiling of disseminated tumor cells. Therefore, the aim of the present study was to explore the value of CTC enumeration and characterization to identify markers associated with the outcome and the aggressiveness of triple-negative breast cancer (TNBC). For that aim, the CTC population from 32 patients diagnosed with TNBC was isolated and characterized. This population showed important cell plasticity in terms of expression of epithelia/mesenchymal and stemness markers, suggesting the relevance of epithelial to mesenchymal transition (EMT) intermediate phenotypes for efficient tumor dissemination. Importantly, the CTC signature demonstrated prognostic value to predict the patients' outcome and pointed to a relevant role of tissue inhibitor of metalloproteinases 1 (TIMP1) and androgen receptor (AR) for TNBC biology. Furthermore, we also analyzed the usefulness of the AR and TIMP1 blockade to target TNBC proliferation and dissemination using in vitro and in vivo zebra fish and mouse models. Overall, the molecular characterization of CTCs from advanced TNBC patients identifies highly specific biomarkers with potential applicability as noninvasive prognostic markers and reinforced the value of TIMP1 and AR as potential therapeutic targets to tackle the most aggressive breast cancer

Role of NOD1 in heart failure progression via regulation of Ca2+ handling

Instituto de Salud Carlos III; CP11/00080Instituto de Salud Carlos III; PI14/01078Ministerio de Economía y competitividad; SAF2014-52492RMinisterio de Economía y competitividad; SAF2014-57190RMinisterio de Economía y competitividad; RTC2015-374

Protocolo de Inducción de Estro en Ovejas de Pelo en Anestro Estacional y su Comportamiento Productivo

The aim of the study was to evaluate the effect of the climate and a heat synchronization protocol on the onset of puberty, gestation and lambing of Texel x Romney ewes bred outside the breeding season. The experiment was carried out at the INTA Experimental Station (EEA) (Corrientes, Argentina) with 26 Texel x Romney ewes of 11 months of age and 47.0 ± 2.2 kg of body weight. A protocol of estrus synchronization using intravaginal sponges with medroxyprogesterone acetate - MAP (60 mg) for seven days and 400 IU of eCG at the removal of the sponges was applied. Two fertile Dorper males were introduced on the day of sponge removal and the diagnosis of pregnancy by rectal ultrasonography was performed 50 days after the mating. Meteorological data were obtained to calculate the temperature-humidity index (ITH) and to determine the degree of caloric stress. Results showed that 69.2% of the sheep were mated at 48 h, 15 ewe-lambs were considered as pregnant and nine of them lambed. During gestation, the sheep were exposed to severe and extreme stress on 23 and 50% of the days. The mean birth weight was 1.5 ± 0.5 kg.El objetivo del estudio fue evaluar el efecto del clima y un protocolo de sincronización de celo sobre el inicio de la pubertad, gestación y parición de borregas Texel x Romney fuera de la estación reproductiva. El experimento se llevó a cabo en la Estación Experimental Agropecuaria (EEA) del INTA (Corrientes, Argentina) con 26 borregas Texel x Romney de 11 meses de edad y 47.0 ± 2.2 kg de peso. Se utilizó un protocolo de sincronización de celo por medio de esponjas intravaginales con acetato de medroxiprogesterona – MAP (60 mg) por siete días y 400 UI de eCG al retiro de las esponjas. Dos machos Dorper fértiles fueron introducidos el día del retiro de las esponjas. El diagnóstico de gestación por ultrasonografía rectal se realizó a los 50 días de la monta. Se obtuvieron datos meteorológicos para calcular el índice de temperatura-humedad (ITH) y determinar el grado de estrés calórico. El 69.2% de las ovejas fueron montadas a las 48 h, 15 borregas fueron consideradas como gestantes y nueve parieron. Durante la gestación, las ovejas estuvieron expuestas a estrés severo y extremo el 23 y 50% de estos días. El promedio de peso al nacer fue 1.5 ± 0.5 kg

Characterization of a genomic signature of pregnancy identified in the breast.

The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer