Bile acids regulate SF-1 to alter cholesterol balance in adrenocortical cells via S1PR2.

Glucocorticoid synthesis typically occurs in adrenal cortex and is influenced by cholesterol balance, since cholesterol is the sole precursor of steroids. Bile acids as the signaling molecules, have been shown to promote steroidogenesis in steroidogenic cells. However, whether bile acids directly regulate cholesterol balance remains elusive. In this study, we prepared cholestatic mouse models and cultured human adrenocortical cells (H295R) treated with taurochenodeoxycholic acid (TCDCA) to determine transcription levels of cholesterol metabolism associated genes and cholesterol concentrations in adrenocortical cells. Results showed that common bile duct ligation (CBDL) and chenodeoxycholic acid (CDCA) feeding elevated the mRNA levels of Abca1, Cyp51, Hmgcr, Srb1, and Mc2r in adrenals of mice. Meanwhile, the concentrations of total cholesterol and cholesteryl ester in adrenals of CBDL and CDCA-fed mice were dramatically lowered. The total and phosphorylation levels of HSL in adrenal glands of CBDL mice were also enhanced. Similarly, TCDCA treatment in H295R cells decreased intracellular concentrations of total cholesterol and cholesteryl ester and increased transcription levels of SRB1, MC2R, and HSL as well. Inhibition of bile acids' receptor sphingosine 1-phosphate receptor 2 (S1PR2), extracellular signal-regulated kinase (ERK) phosphorylation, and steroidogenic factor 1 (SF-1) respectively successfully abolished effect of TCDCA on H295R cells. SF-1s was found to be phosphorylated at Thr75 in TCDCA-treated H295R cells. While a mild increase of intracellular cAMP concentration was detected upon TCDCA treatment, inhibition of PKA activity with Rp-Isomer in H295R cells failed to decrease the expression of SF-1 and its target genes. Our findings suggest that conjugated bile acids affect cholesterol balance through regulation of SF-1 in adrenocortical cells so as to provide an adequate cholesterol supply for glucocorticoid synthesis, which improves and enriches our understanding of the mechanism whereby bile acids regulate cholesterol balance to affect adrenal function.

Plastic Food Packaging from Five Countries Contains Endocrine- and Metabolism-Disrupting Chemicals.

Plastics are complex chemical mixtures of polymers and various intentionally and nonintentionally added substances. Despite the well-established links between certain plastic chemicals (bisphenols and phthalates) and adverse health effects, the composition and toxicity of real-world mixtures of plastic chemicals are not well understood. To assess both, we analyzed the chemicals from 36 plastic food contact articles from five countries using nontarget high-resolution mass spectrometry and reporter-gene assays for four nuclear receptors that represent key components of the endocrine and metabolic system. We found that chemicals activating the pregnane X receptor (PXR), peroxisome proliferator receptor γ (PPARγ), estrogen receptor α (ERα), and inhibiting the androgen receptor (AR) are prevalent in plastic packaging. We detected up to 9936 chemical features in a single product and found that each product had a rather unique chemical fingerprint. To tackle this chemical complexity, we used stepwise partial least-squares regressions and prioritized and tentatively identified the chemical features associated with receptor activity. Our findings demonstrate that most plastic food packaging contains endocrine- and metabolism-disrupting chemicals. Since samples with fewer chemical features induce less toxicity, chemical simplification is key to producing safer plastic packaging.

Beyond the Nucleus: Plastic Chemicals Activate G Protein-Coupled Receptors.

G protein-coupled receptors (GPCRs) are central mediators of cell signaling and physiological function. Despite their biological significance, GPCRs have not been widely studied in the field of toxicology. Herein, we investigated these receptors as novel targets of plastic chemicals using a high-throughput drug screening assay with 126 human non-olfactory GPCRs. In a first-pass screen, we tested the activity of triphenol phosphate, bisphenol A, and diethyl phthalate, as well as three real-world mixtures of chemicals extracted from plastic food packaging covering all major polymer types. We found 11 GPCR-chemical interactions, of which the chemical mixtures exhibited the most robust activity at adenosine receptor 1 (ADORA1) and melatonin receptor 1 (MTNR1A). We further confirm that polyvinyl chloride and polyurethane products contain ADORA1 or MTNRA1 agonists using a confirmatory secondary screen and pharmacological knockdown experiments. Finally, an analysis of the associated gene ontology terms suggests that ADORA1 and MTNR1A activation may be linked to downstream effects on circadian and metabolic processes. This work highlights that signaling disruption caused by plastic chemicals is broader than that previously believed and demonstrates the relevance of nongenomic pathways, which have, thus far, remained unexplored.

Comparing a virtual reality head-mounted display to on-screen three-dimensional visualization and two-dimensional computed tomography data for training in decision making in hepatic surgery: a randomized controlled study.

OBJECTIVE: Evaluation of the benefits of a virtual reality (VR) environment with a head-mounted display (HMD) for decision-making in liver surgery. BACKGROUND: Training in liver surgery involves appraising radiologic images and considering the patient's clinical information. Accurate assessment of 2D-tomography images is complex and requires considerable experience, and often the images are divorced from the clinical information. We present a comprehensive and interactive tool for visualizing operation planning data in a VR environment using a head-mounted-display and compare it to 3D visualization and 2D-tomography. METHODS: Ninety medical students were randomized into three groups (1:1:1 ratio). All participants analyzed three liver surgery patient cases with increasing difficulty. The cases were analyzed using 2D-tomography data (group "2D"), a 3D visualization on a 2D display (group "3D") or within a VR environment (group "VR"). The VR environment was displayed using the "Oculus Rift ™" HMD technology. Participants answered 11 questions on anatomy, tumor involvement and surgical decision-making and 18 evaluative questions (Likert scale). RESULTS: Sum of correct answers were significantly higher in the 3D (7.1 ± 1.4, p < 0.001) and VR (7.1 ± 1.4, p < 0.001) groups than the 2D group (5.4 ± 1.4) while there was no difference between 3D and VR (p = 0.987). Times to answer in the 3D (6:44 ± 02:22 min, p < 0.001) and VR (6:24 ± 02:43 min, p < 0.001) groups were significantly faster than the 2D group (09:13 ± 03:10 min) while there was no difference between 3D and VR (p = 0.419). The VR environment was evaluated as most useful for identification of anatomic anomalies, risk and target structures and for the transfer of anatomical and pathological information to the intraoperative situation in the questionnaire. CONCLUSIONS: A VR environment with 3D visualization using a HMD is useful as a surgical training tool to accurately and quickly determine liver anatomy and tumor involvement in surgery.

Structured feedback and operative video debriefing with critical view of safety annotation in training of laparoscopic cholecystectomy: a randomized controlled study.

BACKGROUND: The learning curve in minimally invasive surgery (MIS) is lengthened compared to open surgery. It has been reported that structured feedback and training in teams of two trainees improves MIS training and MIS performance. Annotation of surgical images and videos may prove beneficial for surgical training. This study investigated whether structured feedback and video debriefing, including annotation of critical view of safety (CVS), have beneficial learning effects in a predefined, multi-modal MIS training curriculum in teams of two trainees. METHODS: This randomized-controlled single-center study included medical students without MIS experience (n = 80). The participants first completed a standardized and structured multi-modal MIS training curriculum. They were then randomly divided into two groups (n = 40 each), and four laparoscopic cholecystectomies (LCs) were performed on ex-vivo porcine livers each. Students in the intervention group received structured feedback after each LC, consisting of LC performance evaluations through tutor-trainee joint video debriefing and CVS video annotation. Performance was evaluated using global and LC-specific Objective Structured Assessments of Technical Skills (OSATS) and Global Operative Assessment of Laparoscopic Skills (GOALS) scores. RESULTS: The participants in the intervention group had higher global and LC-specific OSATS as well as global and LC-specific GOALS scores than the participants in the control group (25.5 ± 7.3 vs. 23.4 ± 5.1, p = 0.003; 47.6 ± 12.9 vs. 36 ± 12.8, p < 0.001; 17.5 ± 4.4 vs. 16 ± 3.8, p < 0.001; 6.6 ± 2.3 vs. 5.9 ± 2.1, p = 0.005). The intervention group achieved CVS more often than the control group (1. LC: 20 vs. 10 participants, p = 0.037, 2. LC: 24 vs. 8, p = 0.001, 3. LC: 31 vs. 8, p < 0.001, 4. LC: 31 vs. 10, p < 0.001). CONCLUSIONS: Structured feedback and video debriefing with CVS annotation improves CVS achievement and ex-vivo porcine LC training performance based on OSATS and GOALS scores.

Safety and efficacy of histotripsy delivery through overlying gas-filled small bowel in an ex vivo swine model.

PURPOSE: To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model. METHODS: An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario. RESULTS: All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively. CONCLUSION: Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.

TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration.

BACKGROUND: The reactivation of genetic programs from early development is a common mechanism for injury-induced organ regeneration. T-box 3 (TBX3) is a member of the T-box family of transcription factors previously shown to regulate pluripotency and subsequent lineage commitment in a number of tissues, including limb and lung. TBX3 is also involved in lung and heart organogenesis. Here, we provide a comprehensive and thorough characterization of TBX3 and its role during pancreatic organogenesis and regeneration. RESULTS: We interrogated the level and cell specificity of TBX3 in the developing and adult pancreas at mRNA and protein levels at multiple developmental stages in mouse and human pancreas. We employed conditional mutagenesis to determine its role in murine pancreatic development and in regeneration after the induction of acute pancreatitis. We found that Tbx3 is dynamically expressed in the pancreatic mesenchyme and epithelium. While Tbx3 is expressed in the developing pancreas, its absence is likely compensated by other factors after ablation from either the mesenchymal or epithelial compartments. In an adult model of acute pancreatitis, we found that a lack of Tbx3 resulted in increased proliferation and fibrosis as well as an enhanced inflammatory gene programs, indicating that Tbx3 has a role in tissue homeostasis and regeneration. CONCLUSIONS: TBX3 demonstrates dynamic expression patterns in the pancreas. Although TBX3 is dispensable for proper pancreatic development, its absence leads to altered organ regeneration after induction of acute pancreatitis.

A target containing phantom for accuracy assessment of cone-beam CT-guided histotripsy.

PURPOSE: Histotripsy is a nonionizing, noninvasive, and nonthermal focal tumor therapy. Cone-beam computed tomography (CBCT) guidance was developed for targeting tumors not visible on ultrasound. This approach assumes cavitation is formed at the geometrical focal point of the therapy transducer. In practice, the exact location might vary slightly between transducers. In this study, we present a phantom with an embedded target to evaluate CBCT-guided histotripsy accuracy and assess the completeness of treatments. METHODS: Spherical (2.8 cm) targets with alternating layers of agar and radiopaque barium were embedded in larger phantoms with similar layers. The layer geometry was designed so that targets were visible on pre-treatment CBCT scans. The actual histotripsy treatment zone was visualized via the mixing of adjacent barium and agar layers in post-treatment CBCT images. CBCT-guided histotripsy treatments of the targets were performed in six phantoms. Offsets between planned and actual treatment zones were measured and used for calibration refinement. To measure targeting accuracy after calibration refinement, six additional phantoms were treated. In a separate investigation, two groups (N = 3) of phantoms were treated to assess visualization of incomplete treatments ("undertreatment" group: 2 cm treatment within 2.8 cm tumor, "mistarget" group: 2.8 cm treatment intentionally shifted laterally). Treatment zones were segmented (3D Slicer 5.0.3), and the centroid distance between the prescribed target and actual treatment zones was quantified. RESULTS: In the calibration refinement group, a 2 mm offset in the direction of ultrasound propagation (Z) was measured. After calibration refinement, the centroid-to-centroid distance between prescribed and actual treatment volumes was 0.5 ± 0.2 mm. Average difference between the prescribed and measured treatment sizes in the incomplete treatment groups was 0.5 ± 0.7 mm. In the mistarget group, the distance between prescribed and measured shifts was 0.2 ± 0.1 mm. CONCLUSION: The proposed prototype phantom allowed for accurate measurement of treatment size and location, and the CBCT visible target provided a simple way to detect misalignments for preliminary quality assurance of CBCT-guided histotripsy.

Technical note: A comparison of physician doses in C-Arm and CT fluoroscopy procedures.

PURPOSE: We address the misconception that the typical physician dose is higher for CT fluoroscopy (CTF) procedures compared to C-Arm procedures. METHODS: We compare physician scatter doses using two methods: a literature review of reported doses and a model based on a modified form of the dose area product (DAP). We define this modified form of DAP, "cumulative absorbed DAP," as the product of the area of the x-ray beam striking the patient, the dose rate per unit area, and the exposure time. RESULTS: The patient entrance dose rate for C-Arm fluoroscopy (0.2 mGy/s) was found to be 15 times lower than for CT fluoroscopy (3 mGy/s). A typical beam entrance area for C-Arm fluoroscopy reported in the literature was found to be 10.6 × 10.6 cm (112 cm2), whereas for CTF was 0.75 × 32 cm (24 cm2). The absorbed DAP rate for C-Arm fluoroscopy (22 mGy*cm2/s) was found to be 3.3 times lower than for CTF (72 mGy*cm2/s). The mean fluoroscopy time for C-Arm procedures (710 s) was found to be 21 times higher than for CT fluoroscopy procedures (23 s). The cumulative absorbed DAP for C-Arm procedures was found to be 9.4 times higher when compared to CT procedures (1.59 mGy*m2 vs. 0.17 mGy*m2). CONCLUSIONS: The higher fluoroscopy time in C-Arm procedures leads to a much lower cumulative DAP (i.e., physician scatter dose) in CTF procedures. This result can inform interventional physicians deciding on whether to perform inter-procedural imaging inside the room as opposed to retreating from the room.

Drug Therapies for Chronic Cholestatic Liver Diseases.

Though ursodeoxycholic acid (UDCA) remains the baseline treatment for most cholestatic liver diseases, UDCA treatment leaves approximately one-third of patients with primary biliary cholangitis (PBC) and all patients with primary sclerosing cholangitis (PSC) at risk for disease progression. New anticholestatic agents, including nuclear receptor agonists, choleretics, and bile acid synthesis suppressors, will likely increase response rates to therapy in PBC and PSC. Strategies that target early immune-mediated injury have so far been disappointing, hampered by the lack of biomarkers to detect early disease states, which then could profit from immunomodulatory therapy. Future concepts need to personalize treatments according to disease stage, progression, and phase, and to combine multiple drugs to target different pathogenic pathways.

Artificial Intelligence-Aided Selection of Needle Pathways: Proof-of-Concept in Percutaneous Lung Biopsies.

PURPOSE: To evaluate the concordance between lung biopsy puncture pathways determined by artificial intelligence (AI) and those determined by expert physicians. MATERIALS AND METHODS: An AI algorithm was created to choose optimal lung biopsy pathways based on segmented thoracic anatomy and emphysema in volumetric lung computed tomography (CT) scans combined with rules derived from the medical literature. The algorithm was validated using pathways generated from CT scans of randomly selected patients (n = 48) who had received percutaneous lung biopsies and had noncontrast CT scans of 1.25-mm thickness available in picture archiving and communication system (PACS) (n = 28, mean age, 68.4 years ± 9.2; 12 women, 16 men). The algorithm generated 5 potential pathways per scan, including the computer-selected best pathway and 4 random pathways (n = 140). Four experienced physicians rated each pathway on a 1-5 scale, where scores of 1-3 were considered safe and 4-5 were considered unsafe. Concordance between computer and physician ratings was assessed using Cohen's κ. RESULTS: The algorithm ratings were statistically equivalent to the physician ratings (safe vs unsafe: κ¯=0.73; ordinal scale: κ¯=0.62). The computer and physician ratings were identical in 57.9% (81/140) of cases and differed by a median of 0 points. All least-cost "best" pathways generated by the algorithm were considered safe by both computer and physicians (28/28) and were judged by physicians to be ideal or near ideal. CONCLUSIONS: AI-generated lung biopsy puncture paths were concordant with expert physician reviewers and considered safe. A prospective comparison between computer- and physician-selected puncture paths appears indicated in addition to expansion to other anatomic locations and procedures.

Lock-in amplifier based peak force infrared microscopy.

Nanoscale infrared (nano-IR) microscopy enables label-free chemical imaging with a spatial resolution below Abbe's diffraction limit through the integration of atomic force microscopy and infrared radiation. Peak force infrared (PFIR) microscopy is one of the emerging nano-IR methods that provides non-destructive multimodal chemical and mechanical characterization capabilities using a straightforward photothermal signal generation mechanism. PFIR microscopy has been demonstrated to work for a wide range of heterogeneous samples, and it even allows operation in the fluid phase. However, the current PFIR microscope requires customized hardware configuration and software programming for real-time signal acquisition and processing, which creates a high barrier to PFIR implementation. In this communication, we describe a type of lock-in amplifier-based PFIR microscopy that can be assembled with generic, commercially available equipment without special hardware or software programming. We demonstrate this method on soft matters of structured polymer blends and blocks, as well as biological cells of E. coli. The lock-in amplifier-based PFIR reduces the entry barrier for PFIR microscopy and makes it a competitive nano-IR method for new users.

Conflicts of Interest in the Assessment of Chemicals, Waste, and Pollution.

Pollution by chemicals and waste impacts human and ecosystem health on regional, national, and global scales, resulting, together with climate change and biodiversity loss, in a triple planetary crisis. Consequently, in 2022, countries agreed to establish an intergovernmental science-policy panel (SPP) on chemicals, waste, and pollution prevention, complementary to the existing intergovernmental science-policy bodies on climate change and biodiversity. To ensure the SPP's success, it is imperative to protect it from conflicts of interest (COI). Here, we (i) define and review the implications of COI, and its relevance for the management of chemicals, waste, and pollution; (ii) summarize established tactics to manufacture doubt in favor of vested interests, i.e., to counter scientific evidence and/or to promote misleading narratives favorable to financial interests; and (iii) illustrate these with selected examples. This analysis leads to a review of arguments for and against chemical industry representation in the SPP's work. We further (iv) rebut an assertion voiced by some that the chemical industry should be directly involved in the panel's work because it possesses data on chemicals essential for the panel's activities. Finally, (v) we present steps that should be taken to prevent the detrimental impacts of COI in the work of the SPP. In particular, we propose to include an independent auditor's role in the SPP to ensure that participation and processes follow clear COI rules. Among others, the auditor should evaluate the content of the assessments produced to ensure unbiased representation of information that underpins the SPP's activities.

SAGES consensus recommendations on surgical video data use, structure, and exploration (for research in artificial intelligence, clinical quality improvement, and surgical education).

BACKGROUND: Surgery generates a vast amount of data from each procedure. Particularly video data provides significant value for surgical research, clinical outcome assessment, quality control, and education. The data lifecycle is influenced by various factors, including data structure, acquisition, storage, and sharing; data use and exploration, and finally data governance, which encompasses all ethical and legal regulations associated with the data. There is a universal need among stakeholders in surgical data science to establish standardized frameworks that address all aspects of this lifecycle to ensure data quality and purpose. METHODS: Working groups were formed, among 48 representatives from academia and industry, including clinicians, computer scientists and industry representatives. These working groups focused on: Data Use, Data Structure, Data Exploration, and Data Governance. After working group and panel discussions, a modified Delphi process was conducted. RESULTS: The resulting Delphi consensus provides conceptualized and structured recommendations for each domain related to surgical video data. We identified the key stakeholders within the data lifecycle and formulated comprehensive, easily understandable, and widely applicable guidelines for data utilization. Standardization of data structure should encompass format and quality, data sources, documentation, metadata, and account for biases within the data. To foster scientific data exploration, datasets should reflect diversity and remain adaptable to future applications. Data governance must be transparent to all stakeholders, addressing legal and ethical considerations surrounding the data. CONCLUSION: This consensus presents essential recommendations around the generation of standardized and diverse surgical video databanks, accounting for multiple stakeholders involved in data generation and use throughout its lifecycle. Following the SAGES annotation framework, we lay the foundation for standardization of data use, structure, and exploration. A detailed exploration of requirements for adequate data governance will follow.

Active learning for extracting surgomic features in robot-assisted minimally invasive esophagectomy: a prospective annotation study.

BACKGROUND: With Surgomics, we aim for personalized prediction of the patient's surgical outcome using machine-learning (ML) on multimodal intraoperative data to extract surgomic features as surgical process characteristics. As high-quality annotations by medical experts are crucial, but still a bottleneck, we prospectively investigate active learning (AL) to reduce annotation effort and present automatic recognition of surgomic features. METHODS: To establish a process for development of surgomic features, ten video-based features related to bleeding, as highly relevant intraoperative complication, were chosen. They comprise the amount of blood and smoke in the surgical field, six instruments, and two anatomic structures. Annotation of selected frames from robot-assisted minimally invasive esophagectomies was performed by at least three independent medical experts. To test whether AL reduces annotation effort, we performed a prospective annotation study comparing AL with equidistant sampling (EQS) for frame selection. Multiple Bayesian ResNet18 architectures were trained on a multicentric dataset, consisting of 22 videos from two centers. RESULTS: In total, 14,004 frames were tag annotated. A mean F1-score of 0.75 ± 0.16 was achieved for all features. The highest F1-score was achieved for the instruments (mean 0.80 ± 0.17). This result is also reflected in the inter-rater-agreement (1-rater-kappa > 0.82). Compared to EQS, AL showed better recognition results for the instruments with a significant difference in the McNemar test comparing correctness of predictions. Moreover, in contrast to EQS, AL selected more frames of the four less common instruments (1512 vs. 607 frames) and achieved higher F1-scores for common instruments while requiring less training frames. CONCLUSION: We presented ten surgomic features relevant for bleeding events in esophageal surgery automatically extracted from surgical video using ML. AL showed the potential to reduce annotation effort while keeping ML performance high for selected features. The source code and the trained models are published open source.

Microplastics could be marginally more hazardous than natural suspended solids - A meta-analysis.

Microplastics (MP) are perceived as a threat to aquatic ecosystems but bear many similarities to suspended sediments which are often considered less harmful. It is, therefore pertinent to determine if and to what extent MP are different from other particles occurring in aquatic ecosystems in terms of their adverse effects. We applied meta-regressions to toxicity data extracted from the literature and harmonized the data to construct Species Sensitivity Distributions (SSDs) for both types of particles. The results were largely inconclusive due to high uncertainty but the central tendencies of our estimates still indicate that MP could be marginally more hazardous compared to suspended sediments. In part, the high uncertainty stems from the general lack of comparable experimental studies and dose-dependent point estimates. We therefore argue that until more comparable data is presented, risk assessors should act precautionary and treat MP in the 1-1000 µm size range as marginally more hazardous to aquatic organisms capable of ingesting such particles.

The Problem of Appetite Loss After Major Abdominal Surgery: A Systematic Review.

OBJECTIVE: To systematically review the problem of appetite loss after major abdominal surgery. SUMMARY OF BACKGROUND DATA: Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited. METHODS: We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489. RESULTS: Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watching cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients. CONCLUSIONS: Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure.

Clustering of self-thermophilic asymmetric dimers: the relevance of hydrodynamics.

Self-thermophilic dimers are characterized by a net phoretic attraction which, in combination with hydrodynamic interactions, results in the formation of crystalline-like aggregates. To distinguish the effect of the different contributions is frequently an important challenge. We present a simulation investigation done in parallel in the presence and the absence of hydrodynamic interactions for the case of asymmetric self-thermophoretic dimers. In the absence of hydrodynamics, the clusters have the standard heads-in configurations. In contrast, in the presence of hydrodynamics, clusters with heads-in conformation are being formed, in which dimers with their propulsion velocity pointing out of the cluster are assembled and stabilized by strong hydrodynamic osmotic flows. Significant variation in the material properties is to be expected from such differences in the collective behavior, whose understanding and control is of great relevance for the development of new synthetic active materials.

Adipogenic Activity of Chemicals Used in Plastic Consumer Products.

Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism-disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized the chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, the chemicals extracted from one-third of the products caused murine 3T3-L1 preadipocytes to proliferate, and differentiate into adipocytes, which were larger and contained more triglycerides than those treated with the reference compound rosiglitazone. Because the majority of plastic extracts did not activate the peroxisome proliferator-activated receptor γ and the glucocorticoid receptor, the adipogenic effects are mediated via other mechanisms and, thus, likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity.