Choristoma is a term which refers to the presence of histologically normal tissue in a heterotopic location; hepatic choristoma is a condition in which hepatic tissue can be found in abnormal ...locations above or below the diaphragm, the gallbladder wall being the most frequent heterotopic site for implantation, this disease is usually asymptomatic and is rarely detected preoperatively with imaging studies due to a general lack of knowledge of this entity. We present the case of a 37 year old male patient who presented with acute abdominal pain in the right upper quadrant, colicky in nature, accompanied by nausea and vomiting; a HIDA 99 mTc scan revealed gallbladder diskynesia as well as a radiolucent bilobulated image. Upon laparoscopy, we encountered two masses on the superoanterior gallbladder wall and Hartmann´s pouch, which upon histopathological specimen examination revealed the presence of hepatic choristoma. This entity should be considered whenever a soft tissue mass is reported on the anterior gallbladder wall on imaging studies; It has been reported that hepatic choristoma is at higher risk for development of hepatocellular carcinoma and should be removed en bloc with the gallbladder.
Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable ...mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking. This chemical modification allows the obtaining of an elastic protein-based hydrogel (GELGYM) with excellent biomimetic properties, approaching those of the native tissue. GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 MPa with compressive strains as high as 80% compared to Gelatin-methacryloyl (GeIMA), the most studied derivative of gelatin used as a bioadhesive. GELGYM is also highly biocompatible and supports cellular adhesion, proliferation, and migration in both 2 and 3-dimensional cell-cultures. These characteristics along with its super adhesion to biological tissues such as cornea, aorta, heart, muscle, kidney, liver, and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation, tissue adhesive, wound dressing, bioprinting, and drug and cell delivery.
Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and ...cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer.
•First report on the use of nanoflowLC-nanoESI-HRMS for pesticide multiresidue analysis.•Use integrated emitters provides an enhancement of method precision and ruggedness.•Limits of quantitation in ...the low ng kg−1 range (ca. 1000-fold lower than MRLs).•Sensitivity achieved enables the use of high dilution factors (1:50 or beyond).•Negligible matrix effects so that matrix-matched calibration is no longer required.
This article reports on the evaluation of nanoflow liquid chromatography-mass spectrometry (LC–MS) for pesticide residue analysis in food. The approach is based on the use of reversed-phase C18nano columns with an integrated emitter, so that separation, ionization and detection are performed minimizing dead volumes. The use of nanoflow not only increases ionization efficiency and minimizes ionization suppression but also boost sensitivity compared to analytical-scale LC–MS methods. The nanoflow LC system was combined with full-scan high resolution mass spectrometry using a Q-Exactive Orbitrap instrument. The analytical performance was assessed for over 60 representative pesticides in five representative commodities (tomato, baby food, orange, fruit-based jam and olive oil). The sensitivity achieved with this configuration enables the implementation of high dilution factors (eg. 1:20, 1:50 or beyond) in pesticide residue workflows without compromising sensitivity, featuring limits of quantitation in the low ng kg−1 range. Using this dilution factors, signal suppression was found negligible in most cases (<10% in most cases, especially with 1:50 dilution), so that matrix-matched standards may be skipped, thus simplifying laboratory workflows. The robustness of the nanoflow LC system and its capability to withstand long analytical runs was also evaluated. Appropriate precision in terms of peak area and retention time was obtained at different concentration levels for over 125 injections without any instrument servicing. The main benefits of the nanoflow liquid chromatography approach are the high sensitivity gain and the outstanding reduction in matrix effects thanks to the high sample dilution factors that can be implemented, along with the substantial reduction in solvent usage.
Scope
Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also ...associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well‐characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome.
Methods
Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg−1). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium‐dependent vasodilator response to acetylcholine.
Results
LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice.
Conclusion
The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.
The aim of this study is the evaluation of Lippia Citriodora extract (LCE) treatment on diet‐induced obesity in mice. LCE administration ameliorates induced obesity, enhancing the inflammatory status and the vascular functionality. Furthermore, it is the first time that LCE treatment is shown to modulate the gut microbiota. These findings support the use of LCE as a new functional food in metabolic syndrome.
A wildland fire is an uncontrolled fire that occurs mainly in forest areas, although it can also invade urban or agricultural areas. Among the main causes of wildfires, human factors, either ...intentional or accidental, are the most usual ones. The number and impact of forest fires are expected to grow as a consequence of the global warming. In order to fight against these disasters, it is necessary to adopt a comprehensive, multifaceted approach that enables a continuous situational awareness and instant responsiveness. This paper describes a hierarchical wireless sensor network aimed at early fire detection in risky areas, integrated with the fire fighting command centres, geographical information systems, and fire simulators. This configuration has been successfully tested in two fire simulations involving all the key players in fire fighting operations: fire brigades, communication systems, and aerial, coordination, and land means.
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) integrates cellular nutrient signaling and hormonal cues to control metabolism. We have previously shown that constitutive nutrient ...signaling to mTORC1 by means of genetic activation of
RagA
(expression of GTP-locked RagA, or RagA
GTP
) in mice resulted in a fatal energetic crisis at birth. Herein, we rescue neonatal lethality in
RagA
GTP
mice and find morphometric and metabolic alterations that span glucose, lipid, ketone, bile acid and amino acid homeostasis in adults, and a median lifespan of nine months. Proteomic and metabolomic analyses of livers from
RagA
GTP
mice reveal a failed metabolic adaptation to fasting due to a global impairment in PPARα transcriptional program. These metabolic defects are partially recapitulated by restricting activation of RagA to hepatocytes, and revert by pharmacological inhibition of mTORC1. Constitutive hepatic nutrient signaling does not cause hepatocellular damage and carcinomas, unlike genetic activation of growth factor signaling upstream of mTORC1. In summary, RagA signaling dictates dynamic responses to feeding-fasting cycles to tune metabolism so as to match the nutritional state.
Around, 30-40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. ...Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer.
Studies specifically designed to determine the profile of psychiatric symptoms among COVID-19 patients are limited and based on case series, self-report questionnaires, and surveys. The objective of ...the study was to identify and classify the neuropsychological symptoms of hospitalized COVID-19 patients during the first wave of the pandemic in one of the most important front-line tertiary hospitals from Spain, and to analyze its correlation with diagnosed mental disorders, as well as to explore potential risk factors associated with mental health problems. This observational, cohort study involved data from COVID-19 patients at the University Hospital 12 de Octubre (Madrid, Spain) from February to May 2020. First, patients underwent a semistructured phone interview (screening phase), based on the Mini International Neuropsychiatric Interview (MINI). Then the confirmation of the diagnosis (confirmation phase) was performed in patients who reported a mental disorder development or worsening. A factorial analysis was performed to identify groups of symptoms. A tetrachoric matrix was created, and factorial analysis, by a principal component analysis, was employed upon it. Factors showing values >1.0 were selected, and a varimax rotation was applied to these factors. Symptoms most frequently identified in patients were anosmia/ageusia (54.6%), cognitive complaints (50.3%), worry/nervousness (43.8%), slowing down (36.2%), and sadness (35.4%). Four factors were identified after the screening phase. The first ("anxiety/depression") and second ("executive dysfunction") factors explained 45.4 and 11.5% of the variance, respectively. Women, age between 50 and 60 years, duration in the hospital (more than 13 days), and psychiatric history showed significant higher levels (number of symptoms) in the factors. This study reports the factor structure of the psychiatric symptoms developed by patients with a confirmed diagnosis of SARS-CoV2 during the first wave of the COVID-19. Three item domains (anxiety, depression, and posttraumatic stress disorder symptoms) were loaded together on one factor, whereas sleep disturbance stood up as a separate factor. Interestingly, the item anosmia/ageusia was not captured by any factor. In conclusion, an increase in neuropsychiatric morbidity is expected in the upcoming months and years. Therefore, screening for early symptoms is the first step to prevent mental health problems associated with this pandemic.
Thanks to technological advances, the administration of cognitive assessments
via
digital solutions continues to increase, both in research and clinical practice. “Guttmann Cognitest”
°ledR
is a ...digital solution for cognitive assessment which includes seven computerized tasks designed to assess main cognitive functions requiring approximately 20 min to be completed. The purpose of the present study was to validate it against standard and more extensive in-person neuropsychological assessments in the context of the Barcelona Brain Health Initiative (BBHI) cohort study. We studied 274 participants of the BBHI (126 women, mean age = 56.14, age range 44–69), who underwent an extensive in-person assessment, including a classical paper-and-pencil neuropsychological assessment and a cognitive assessment
via
the “Guttmann Cognitest”
°ledR
. Principal component analysis indicated that “Guttmann Cognitest”
°ledR
measures four main cognitive domains and convergent validity analysis demonstrated that cognitive performance was associated with gold standard paper and pencil tests. Results also showed an expected negative correlation with age, a relation with educational level as well as a gender effect. Regression-based norming equations for the sample tested are also reported. Performing a cognitive assessment with this digital solution is feasible and potentially useful to gather information about cognitive functioning in large samples and experimental settings.
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