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An increasing number of patients with colorectal cancer (CRC) are presenting with synchronous disease to the liver. The optimal surgical approach for this complex patient group is controversial, but ultimately depends on individual patient characteristics and institutional practices. Surgical strategies include the traditional staged approach, a combined colorectal and liver resection, or a liver-first reverse approach. In this review, the authors will provide an overview of each strategy, including case examples demonstrating the benefits of the more recently described liver-first approach, while arguing for individualized planning and multidisciplinary discussion for every patient. 2020 Hepatobiliary Surgery and Nutrition. All rights reserved.Background Patients with advanced hepatobiliary cancer (HBC) have a dismal prognosis and limited treatment options. Immunotherapy has been considered as a promising treatment, especially for cancers not amenable to surgery. Methods Between 2004, and 2015, patients diagnosed with hepatocellular carcinoma (HCC), intra- and extrahepatic cholangiocarcinoma and gallbladder cancer (GBC) were identified in the National Cancer Database. Results Among 249,913 patients with HBC, only 585 (0.2%) patients received immunotherapy. Among patients who received immunotherapy, most patients were diagnosed between 2012 and 2015, had private insurance, as well as an income ≥$46,000 and were treated at an academic facility. The use of immunotherapy among HBC patients varied by diagnosis (HCC, 67.7%; bile duct cancer, 14%). On multivariable analysis, a more recent period of diagnosis (OR 1.80, 95% CI 1.44-2.25), median income >$46,000 (OR 1.43, 95% CI 1.11-1.87), and higher tumor stage (stage III, OR 2.22, 95% CI 1.65-3.01; stage IV, OR 3.24, 95% CI 2.41-4.34) were associated with greater odds of receiving immunotherapy. Conclusions Overall utilization of immunotherapy in the US among patients with HBC was very low, yet has increased over time. Certain socioeconomic factors were associated with an increased likely of receiving immunotherapy, suggesting disparities in access of patients with lower socioeconomic status. 2020 Hepatobiliary Surgery and Nutrition. All rights reserved.Background Previous research has demonstrated that specific radiographic criteria, including the presence of calcifications and the enhancement pattern on computed tomography (CT) imaging, correlates with clinicopathologic features and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (NET). We sought to investigate whether these radiographic characteristics were prognostic among patients with neuroendocrine liver metastases (NELM) undergoing surgical resection. Methods The preoperative contrast-enhanced CT scans of all patients who underwent resection of NELM at a single institution between 2000-2015 were retrospectively reviewed. The presence of calcifications was determined on non-contrast phase imaging. Enhancement on the arterial phase scan was categorized as hyperenhancing, hypoenhancing, or mixed. Relevant clinicopathologic characteristics as well as recurrence-free survival (RFS) and overall survival (OS) were compared between groups. Results Among 82 patients who underwent resectstics, RFS (P=0.618) or OS (P=0.268). Conclusions Radiographic characteristics on contrast-enhanced CT are not associated with the outcomes of patients undergoing resection of NELM. Future investigations should evaluate the prognostic impact of functional neuroendocrine imaging. 2020 Hepatobiliary Surgery and Nutrition. All rights reserved.The aim of the study was to evaluate the job satisfaction of official veterinarians working in the field of animal welfare control and identify both positive features and challenges of their work. An electronic questionnaire was designed to evaluate job satisfaction. The questionnaire was responded to by 73 of the 98 Finnish official veterinarians working in the field of animal welfare control. The Spearman's rank correlation coefficient was used to evaluate the relation between stress and different work-related factors. More than half of the respondents reported work-related stress or fatigue. Threatening situations, disturbed work-private life balance and a high amount of overtime work were found to be frequent underlying causes of stress. Fieldwork, especially when working alone, was perceived as the most challenging part of the work. Of the respondents, three out of four performed animal welfare inspections mainly alone. Although the respondents reported getting additional help to perform an inspection most of the times they needed it, a wish to work in a pair was highlighted. The results of the present study indicate that official veterinarians often experience work-related stress and fatigue. By testing interventions shown to be beneficial, such as providing adequate support within the work community, decreasing the workload and enabling inspections to be done in pairs, job satisfaction could be improved. Copyright © 2020 Väärikkälä, Hänninen and Nevas.Aging is associated with structural and functional changes in the heart and is a major risk factor in developing cardiovascular disease. Many recent studies have focused on increasing our understanding of the basis of aging at the cellular and molecular levels in various tissues, including the heart. It is known that there is an age-related decline in cellular quality control pathways such as autophagy and mitophagy, which leads to accumulation of potentially harmful cellular components in cardiac myocytes. There is evidence that diminished autophagy and mitophagy accelerate the aging process, while enhancement preserves cardiac homeostasis and extends life span. Here, we review the current knowledge of autophagy and mitophagy in aging and discuss how age-associated alterations in these processes contribute to cardiac aging and age-related cardiovascular diseases. Copyright © 2020 Liang and Gustafsson.There is growing interest in the metabolism of ketones owing to their reported benefits in neurological and more recently in cardiovascular and renal diseases. As an alternative to a very high fat ketogenic diet, ketones precursors for oral intake are being developed to achieve ketosis without the need for dietary carbohydrate restriction. Here we report that an oral D-beta-hydroxybutyrate (D-BHB) supplement is rapidly absorbed and metabolized in humans and increases blood ketones to millimolar levels. At the same dose, D-BHB is significantly more ketogenic and provides fewer calories than a racemic mixture of BHB or medium chain triglyceride. In a whole body ketone positron emission tomography pilot study, we observed that after D-BHB consumption, the ketone tracer 11C-acetoacetate is rapidly metabolized, mostly by the heart and the kidneys. Beyond brain energy rescue, this opens additional opportunities for therapeutic exploration of D-BHB supplements as a "super fuel" in cardiac and chronic kidney diseases. Copyright © 2020 Cuenoud, Hartweg, Godin, Croteau, Maltais, Castellano, Carpentier and Cunnane.[This corrects the article DOI 10.3389/fnut.2019.00045.]. Copyright © 2020 Lackey, Williams, Meehan, Zachek, Benda, Price, Foster, Sellen, Kamau-Mbuthia, Kamundia, Mbugua, Moore, Prentice, K., Kvist, Otoo, García-Carral, Jiménez, Ruiz, Rodríguez, Pareja, Bode, McGuire and McGuire.Three-dimensional gastrointestinal organoid culture systems provide innovative and tractable models to investigate fundamental developmental biology questions using human cells. The goal of this study was to explore the role of the zinc-finger containing transcription factor GATA4 in gastric development using an organoid-based model of human stomach development. Given GATA4's vital role in the developing mouse gastrointestinal tract, we hypothesized that GATA4 plays an essential role in human stomach development. We generated a human induced pluripotent stem cell (hiPSC) line stably expressing an shRNA targeted against GATA4 (G4KD-hiPSCs) and used an established protocol for the directed differentiation of hiPSCs into stomach organoids. This in vitro model system, informed by studies in multiple non-human model systems, recapitulates the fundamental processes of stomach development, including foregut endoderm patterning, specification, and subsequent tissue morphogenesis and growth, to produce three-dimensional fundic or antral organoids containing functional gastric epithelial cell types. We confirmed that GATA4 depletion did not disrupt hiPSC differentiation to definitive endoderm (DE). However, when G4KD-hiPSC-derived DE cells were directed to differentiate toward budding SOX2+, HNF1B+ posterior foregut spheroids, we observed a striking decrease in the emergence of cell aggregates, with little to no spheroid formation and budding by GATA4-depleted hiPSCs. In contrast, control hiPSC-derived DE cells, expressing GATA4, formed aggregates and budded into spheroids as expected. These data support an essential role for GATA4 during the earliest stages of human stomach development. Copyright © 2020 DeLaForest, Quryshi, Frolkis, Franklin and Battle.Objective To determine the relationship between maternal bone resorption and bone development in fetuses. Methods Female SD rats were injected with either fluorescent calcium indicator calcein alone or together with tetracycline 1 week before pregnancy, followed by fluorescence detection in fetal tibias 21 days post-treatment. Alendronate was subsequently administered to pregnant rats to inhibit maternal bone resorption, while maternal bone turnover and fetal bone development were both examined. Results The maternal fluorescent labeled calcium before pregnancy was found in the fetal tibia. This indicated that the calcium of maternal bones may be released into the maternal circulation through high bone resorption during pregnancy, thereby participating in the fetal bone development. Bone histomorphometry and serum biomarker results showed that Alendronate significantly inhibited maternal bone resorption in pregnant rats when compared to normal pregnant rats. Moreover, the body weight, bone mass, and bone length of the fetuses in the Alendronate group were significantly decreased; while no apparent abnormality in placental morphology was observed. The above results implied that when maternal bone resorption is suppressed, the development of the fetal bone shall also be suppressed. Conclusion Calcium in the maternal bone is released into the maternal circulation through bone resorption during pregnancy which represents an important material source in fetal bone development. Therefore, high bone turnover during pregnancy is essential for mammalian embryonic bone development. Copyright © 2020 Jia, Rao, Miu, Tang, Chen, Yang, Li, Li, Chen and Lu.Biomeshes based on decellularized bovine pericardium (DBP) are widely used in reconstructive surgery due to their wide availability and the attractive biomechanical properties. However, their efficacy in clinical applications is often affected by the uncontrolled immunogenicity and proteolytic degradation. To address this issue, we present here in vivo multiparametric imaging analysis of epoxy crosslinked DBPs to reveal their fate after implantation. We first analyzed the structure of the crosslinked DBP using scanning electron microscopy and evaluated proteolytic stability and cytotoxicity. R-848 supplier Next, using combination of fluorescence and hypoxia imaging, X-ray computed microtomography and histology techniques we studied the fate of DBPs after subcutaneous implantation in animals. Our approach revealed high resistance to biodegradation, gradual remodeling of a surrounding tissue forming the connective tissue capsule and calcification of crosslinked DBPs. These changes were concomitant to the development of hypoxia in the samples within 3 weeks after implantation and subsequent induction of angiogenesis and vascularization.

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