Correction: Martins et al. Cannabis-Based Products for the Treatment of Skin Inflammatory Diseases: A Timely Review. Pharmaceuticals 2022, 15, 210.

The authors would like to make the following corrections about the published paper [...].

Seroprevalence of SARS-CoV-2 on health professionals via Bayesian estimation: a Brazilian case study before and after vaccines.

The increasing number of COVID-19 infections brought by the current pandemic has encouraged the scientific community to analyze the seroprevalence in populations to support health policies. In this context, accurate estimations of SARS-CoV-2 antibodies based on antibody tests metrics (e.g., specificity and sensitivity) and the study of population characteristics are essential. Here, we propose a Bayesian analysis using IgA and IgG antibody levels through multiple scenarios regarding data availability from different information sources to estimate the seroprevalence of health professionals in a Northeastern Brazilian city: no data available, data only related to the test performance, data from other regions. The study population comprises 432 subjects with more than 620 collections analyzed via IgA/IgG ELISA tests. We conducted the study in pre- and post-vaccination campaigns started in Brazil. We discuss the importance of aggregating available data from various sources to create informative prior knowledge. Considering prior information from the USA and Europe, the pre-vaccine seroprevalence means are 8.04% and 10.09% for IgG and 7.40% and 9.11% for IgA. For the post-vaccination campaign and considering local informative prior, the median is 84.83% for IgG, which confirms a sharp increase in the seroprevalence after vaccination. Additionally, stratification considering differences in sex, age (younger than 30 years, between 30 and 49 years, and older than 49 years), and presence of comorbidities are provided for all scenarios.

Cannabis-Based Products for the Treatment of Skin Inflammatory Diseases: A Timely Review.

The use of natural products in dermatology is increasingly being pursued due to sustainability and ecological issues, and as a possible way to improve the therapeutic outcome of chronic skin diseases, relieving the burden for both patients and healthcare systems. The legalization of cannabis by a growing number of countries has opened the way for researching the use of cannabinoids in therapeutic topical formulations. Cannabinoids are a diverse class of pharmacologically active compounds produced by Cannabis sativa (phytocannabinoids) and similar molecules (endocannabinoids, synthetic cannabinoids). Humans possess an endocannabinoid system involved in the regulation of several physiological processes, which includes naturally-produced endocannabinoids, and proteins involved in their transport, synthesis and degradation. The modulation of the endocannabinoid system is a promising therapeutic target for multiple diseases, including vascular, mental and neurodegenerative disorders. However, due to the complex nature of this system and its crosstalk with other biological systems, the development of novel target drugs is an ongoing challenging task. The discovery of a skin endocannabinoid system and its role in maintaining skin homeostasis, alongside the anti-inflammatory actions of cannabinoids, has raised interest in their use for the treatment of skin inflammatory diseases, which is the focus of this review. Oral treatments are only effective at high doses, having considerable adverse effects; thus, research into plant-based or synthetic cannabinoids that can be incorporated into high-quality, safe topical products for the treatment of inflammatory skin conditions is timely. Previous studies revealed that such products are usually well tolerated and showed promising results for example in the treatment of atopic dermatitis, psoriasis, and contact dermatitis. However, further controlled human clinical trials are needed to fully unravel the potential of these compounds, and the possible side effects associated with their topical use.

Post-synthetic modification of aluminum trimesate and copper trimesate with TiO2 nanoparticles for photocatalytic applications.

Organic pollutants have been a significant source of concern in recent years due to their facile dissemination and harmful effects. In this work, two different metal-organic frameworks (MOFs) were initially prepared by hydrothermal treatment, namely aluminum trimesate (MIL-100(Al)) and copper trimesate (HKUST-1). These materials were subsequently submitted to a post-synthetic modification step to grow titania nanoparticles on their surface. Anatase nanoparticles with sizes around 5 nm were successfully anchored on MIL-100(Al), and the concentration of TiO2 in this sample was about 68 wt.%. This is the first time that this composite (TiO2@MIL-100(Al)) is reported in the literature. It showed an improved photocatalytic activity, removing 90% of methylene blue (k app = 1.29 h-1), 55% of sodium diclofenac (k app = 0.21 h-1), and 62% of ibuprofen (k app = 0.37 h-1) after four hours of illumination with UV-A light. A significant concentration (14 µM) of reactive oxygen species (ROS) was detected for this composite. HKUST-1 showed a structural collapse during its post-synthetic modification, leading to a non-porous material and providing fewer sites for the heterogeneous nucleation of titania. This behavior led to a low concentration of rutile nanoparticles on HKUST-1 (9 wt.%). However, the obtained composite (TiO2@HKUST) also showed an improved photoactivity compared to HKUST-1, increasing the photodegradation rates evaluated for methylene blue (0.05 h-1 vs. 0.29 h-1), sodium diclofenac (negligible vs. 0.03 h-1), and ibuprofen (0.01 h-1 vs. 0.02 h-1). This work brings new insights concerning the preparation of photocatalysts by growing semiconductor nanoparticles on trimesate-based MOFs.

Effects of protein source and lipid supplementation on conservation and feed value of total mixed ration silages for finishing beef cattle.

The objective of this study was to examine the conservation process and feed value of total mixed ration (TMR) silages. In exp. 1, we evaluated the fermentation pattern and aerobic stability of TMR silages containing different protein and lipid supplementations. In exp. 2, we compared the performance of finishing beef heifers fed those TMR silages. In both experiments, treatments were as follows: ensiled TMR with urea (U); ensiled TMR without a protein supplement at ensiling, but soybean meal supplemented at feeding to balance diet crude protein (CP) in exp. 2 (SMnf; where the acronym nf indicates nonfermented); ensiled TMR with soybean meal (SM); and ensiled TMR with rolled soybean grain (SG). Thirty-two Nellore heifers (313 ± 8.8 kg shrunk body weight [SBW]) were blocked by initial SBW, housed in individual pens, and enrolled in exp. 2 for 82 d. In exp. 1, treatment without a protein supplement (SMnf) had a lower content of CP, soluble CP, NH3-N, pH, and Clostridium count compared with U (P ≤ 0.03). Lactic acid concentrations tended to be reduced for SMnf compared with U (P = 0.09). Ethanol concentration was reduced in SG compared with SM (P < 0.01). 1,2-Propanediol concentration was increased in SMnf compared with U (P < 0.01), reduced in SM compared with SMnf (P = 0.02), and increased in SG compared with SM (P = 0.02). Dry matter (DM) loss during fermentation was low and similar among treatments (~3.7%). All silages remained stable during 10 d of aerobic exposure after feed out. Considering fermentation traits, such as pH (≤4.72), NH3-N (<10% of N, except for U treatment), butyric acid (<0.05 % DM), and DM losses (<3.70% DM), all silages can be considered well conserved. In exp. 2, diets were isonitrogenous because soybean meal was added to SMnf before feeding. Compared with SM, cattle fed SG made more meals per day (P = 0.04) and tended to have a decreased intermeal interval (P = 0.09). DM intake, average daily gain, final SBW, hot carcass weight, Biceps femoris fat thickness, and serum levels of triglycerides and cholesterol were increased for SG compared with SM (P ≤ 0.05). In brief, TMR silages exhibited an adequate fermentation pattern and high aerobic stability. The supplementation of true protein did not improve animal performance, whereas the addition of soybean grain as a lipid source improved the performance of finishing cattle fed TMR silages.

Effects of processing, moisture, and storage length on the fermentation profile, particle size, and ruminal disappearance of reconstituted corn grain.

Our objective was to examine the effects of processing, moisture, and anaerobic storage length of reconstituted corn grain (RCG) on the fermentation profile, geometric mean particle size (GMPS), and ruminal dry matter disappearance (DMD). Dry corn kernels were ground (hammer mill, 5-mm screen) or rolled, then rehydrated to 30%, 35%, or 40% moisture, and stored for 0, 14, 30, 60, 90, 120, or 180 d in laboratory silos. Rolled corn had an increased GMPS compared with ground corn (2.24 and 1.13 mm, respectively, at ensiling). However, there was a trend for an interaction between processing and moisture concentration to affect particle size, with GMPS increasing with increased moisture concentration, especially in ground corn. Longer storage periods also slightly increased GMPS. Processing, moisture, and storage length interacted to affect the fermentation pattern (two- or three-way interactions). Overall, pH decreased, whereas lactic acid, acetic acid, ethanol, and NH3-N increased with storage length. RCG with 30% moisture had less lactic acid than corn with 35% and 40% moisture, indicating that fermentation might have been curtailed and also due to the clostridial fermentation that converts lactic acid to butyric acid. Ensiling reconstituted ground corn with 30% of moisture led to greater concentrations of ethanol and butyric acid, resulting in greater DM loss than grain rehydrated to 35% or 40% of moisture. Ammonia-N and in situ ruminal DMD were highest for reconstituted ground corn with 35% or 40% of moisture, mainly after 60 d of storage. Therefore, longer storage periods and greater moisture contents did not offset the negative effect of greater particle size on the in situ ruminal DMD of rolled RCG. Nonetheless, RCG should be ensiled with more than 30% moisture and stored for at least 2 mo to improve the ruminal DMD and reduce the formation of ethanol and butyric acid.

Breaking Bad News: A Study on Formal Training in a High-Risk Obstetrics Setting.

Background: Breaking bad news is a frequent task in high-risk obstetrics clinics. Few studies have examined the role of training in improving such a difficult medical task. Aim: To evaluate the influence of a training program on the participants' perceptions of bad news communication at a high-risk obstetrics center. Design: This prospective study was conducted at the Department of Obstetrics/Gynecology, Hospital das Clinicas, from March 2016 to May 2017. Setting/Participants: Maternal-fetal health specialists were invited to complete an institutional questionnaire based on the SPIKES protocol for communicating bad news before and after training. The training consisted of theoretical lectures and small group practice using role play. The questionnaire responses were compared using nonparametric tests to evaluate the differences in physicians' perceptions at the two timepoints. The questionnaire items were evaluated individually and in groups following the communication steps of the SPIKES protocol. Results: In total, 110 physicians were invited to participate. Ninety completed the pretraining questionnaire and 40 answered the post-training questionnaire. After training, there were significant improvements in knowing how to prepare the environment before delivering bad news (p = 0.010), feeling able to transmit bad news (p < 0.001), and to discuss the prognosis (p = 0.026), feeling capable of discussing ending the pregnancy (p = 0.003), and end-of-life issues (p = 0.007) and feeling confident about answering difficult questions (p = 0.004). The comparison of the grouped responses following the steps of the SPIKES protocol showed significant differences for "knowledge" (p < 0.001), "emotions," (p = 0.004) and "strategy and summary" (p = 0.002). Conclusion: The implementation of institutional training in breaking bad news changed the perception of the physicians in the communication setting.

A Carbon-Fiber Sheet Resistor for MR-, CT-, SPECT-, and PET-Compatible Temperature Maintenance in Small Animals.

A magnetic resonance (MR)-, computed tomography (CT)-, single-photon emission computed tomography (SPECT)-, and positron emission tomography (PET)-compatible carbon-fiber sheet resistor for temperature maintenance in small animals where space limitations prevent the use of circulating fluids was developed. A 250 Ω carbon-fiber sheet resistor was mounted to the underside of an imaging cradle. Alternating current, operating at 99 kHz, and with a power of 1-2 W, was applied to the resistor providing a cradle base temperature of ∼37°C. Temperature control was implemented with a proportional-integral-derivative controller, and temperature maintenance was demonstrated in 4 mice positioned in both MR and PET/SPECT/CT scanners. MR and CT compatibility were also shown, and multimodal MR-CT-PET-SPECT imaging of the mouse abdomen was performed in vivo. Core temperature was maintained at 35.5°C ± 0.2°C. No line-shape, frequency, or image distortions attributable to the current flow through the heater were observed on MR. Upon CT imaging, no heater-related artifacts were observed when carbon-fiber was used. Multimodal imaging was performed and images could be easily coregistered, displayed, analyzed, and presented. Carbon fiber sheet resistors powered with high-frequency alternating current allow homeothermic maintenance that is compatible with multimodal imaging. The heater is small, and it is easy to produce and integrate into multimodal imaging cradles.

Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2.

Because metastasis is associated with the majority of cancer-related deaths, its prevention is a clinical aspiration. Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long-term administration of aspirin leads to reduced distant metastases in murine models and clinical trials, but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. Here, we have shown that aspirin dramatically reduced lung metastasis through inhibition of COX-1 while the cancer cells remained intravascular and that inhibition of platelet COX-1 alone was sufficient to impair metastasis. Thromboxane A2 (TXA2) was the prostanoid product of COX-1 responsible for this antimetastatic effect. Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, tumor cell adhesion to the endothelium, and recruitment of metastasis-promoting monocytes/macrophages, and diminished the formation of a premetastatic niche. Thus, platelet-derived TXA2 orchestrates the generation of a favorable intravascular metastatic niche that promotes tumor cell seeding and identifies COX-1/TXA2 signaling as a target for the prevention of metastasis.

Cardio-Respiratory synchronized bSSFP MRI for high throughput in vivo lung tumour quantification.

The identification and measurement of tumours is a key requirement in the study of tumour development in mouse models of human cancer. Disease burden in autochthonous tumours, such as those arising in the lung, can be seen with non-invasive imaging, but cannot be accurately measured using standard tools such as callipers. Lung imaging is further complicated in the mouse due to instabilities arising from the rapid but cyclic cardio-respiratory motions, and the desire to use free-breathing animals. Female A/JOlaHsd mice were either injected (i.p.) with PBS 0.1ml/10g body weight (n = 6), or 10% urethane/PBS 0.1ml/10g body weight (n = 12) to induce autochthonous lung tumours. Cardio-respiratory synchronised bSSFP MRI, at 200 µm isotropic resolution was performed at 8, 13 and 18 weeks post induction. Images from the same mouse at different time points were aligned using threshold-based segmented masks of the lungs (ITK-SNAP and MATLAB) and tumour volumes were determined via threshold-based segmentation (ITK-SNAP).Scan times were routinely below 10 minutes and tumours were readily identifiable. Image registration allowed serial measurement of tumour volumes as small as 0.056 mm3. Repetitive imaging did not lead to mouse welfare issues. We have developed a motion desensitised scan that enables high sensitivity MRI to be performed with high throughput capability of greater than 4 mice/hour. Image segmentation and registration allows serial measurement of individual, small tumours. This allows fast and highly efficient volumetric lung tumour monitoring in cohorts of 30 mice per imaging time point. As a result, adaptive trial study designs can be achieved, optimizing experimental and welfare outcomes.

The digestive tube of Piaractus brachypomus: gross morphology, histology/histochemistry of the mucosal layer and the effects of parasitism by Neoechinorhynchus sp.

The objective of the present study was to describe the histology and histochemistry of the mucosal layer of the digestive tube of Piaractus brachypomus, and the histopathology associated with parasitism by Neoechinorhynchus sp. The digestive tube of P. brachypomus consists of three macroscopically distinct portions: short, rectilinear and elastic-walled ooesophagus, J-shaped siphon stomach and a long intestine with rectilinear and curved portions, defined by patterns of villi as foregut, midgut, and hindgut. Histological and histochemical differences were observed in the mucosal layers of the different digestive tube regions, such as intense production of neutral and acidic mucous substances in the pseudostratified mucosal epithelium of the oesophagus; positive periodic acid Schiff reagent (PAS)reactions at the apex of the columnar epithelial cells of the stomach and increased intensity of histochemical reactions in the hindgut region. Neoechinorhynchus sp. was present in 85.7% of specimens examined, with a mean intensity of 7.4 ± 6.2 (±) and abundance of 6.33. Good health of the fish indicated by high relative condition factor values ( Kn ) and occurrence of only mild to moderate alteration in the mucosal layer indicated that Neoechinorhynchus sp. exhibits low pathogenicity towards P. brachypomus hosts in farming environments, with low levels of infection.

Prospective gating control for highly efficient cardio-respiratory synchronised short and constant TR MRI in the mouse.

PURPOSE: Cardiac and respiratory motion derived image artefacts are reduced when data are acquired with cardiac and respiratory synchronisation. Where steady state imaging techniques are required in small animals, synchronisation is most commonly performed using retrospective gating techniques but these invoke an inherent time penalty. This paper reports the development of prospective gating techniques for cardiac and respiratory motion desensitised MRI with significantly reduced minimum scan time compared to retrospective gating. METHODS: Prospective gating incorporating the automatic reacquisition of data corrupted by motion at the entry to each breath was implemented in short TR 3D spoiled gradient echo imaging. Motion sensitivity was examined over the whole mouse body for scans performed without gating, with respiratory gating, and with cardio-respiratory gating. The gating methods were performed with and without automatic reacquisition of motion corrupted data immediately after completion of the same breath. Prospective cardio-respiratory gating, with acquisition of 64 k-space lines per cardiac R-wave, was used to enable whole body DCE-MRI in the mouse. RESULTS: Prospective cardio-respiratory gating enabled high fidelity steady state imaging of physiologically mobile organs such as the heart and lung. The automatic reacquisition of data corrupted by motion at the entry to each breath minimised respiratory motion artefact and enabled a highly efficient data capture that was adaptive to changes in the inter-breath interval. Prospective cardio-respiratory gating control enabled DCE-MRI to be performed over the whole mouse body with the acquisition of successive image volumes every 12-15 s at 422 µm isotropic resolution. CONCLUSIONS: Highly efficient cardio-respiratory motion desensitised steady state MRI can be performed in small animals with prospective synchronisation, centre-out phase-encode ordering, and the automatic reacquisition of data corrupted by motion at the entry to each breath. The method presented is robust against spontaneous changes in the breathing rate. Steady state imaging with prospective cardio-respiratory gating is much more efficient than with retrospective gating, and enables the examination of rapidly changing systems such as those found when using DCE-MRI.

A DCE-MRI Driven 3-D Reaction-Diffusion Model of Solid Tumor Growth.

Predicting tumor growth and its response to therapy remains a major challenge in cancer research and strongly relies on tumor growth models. In this paper, we introduce, calibrate, and verify a novel image-driven reaction-diffusion model of avascular tumor growth. The model allows for proliferation, death and spread of tumor cells, and accounts for nutrient distribution and hypoxia. It is constrained by longitudinal time series of dynamic contrast-enhancement-MRI images. Tumor specific parameters are estimated from two early time points and used to predict the spatio-temporal evolution of the tumor volume and cell densities at later time points. We first test our parameter estimation approach on synthetic data from 15 generated tumors. Our in silico study resulted in small volume errors (<5%) and high Dice overlaps (>97%), showing that model parameters can be successfully recovered and used to accurately predict the tumor growth. Encouraged by these results, we apply our model to seven pre-clinical cases of breast carcinoma. We are able to show promising preliminary results, especially for the estimation for early time points. Processes like angiogenesis and apoptosis should be included to further improve predictions for later time points.

Refinement of in vivo optical imaging: Development of a real-time respiration monitoring system.

In vivo optical imaging enables detection and quantification of light-emitting compounds from the whole body in small animals such as the mouse, but it typically requires the use of anaesthetics for subject immobilisation due to long exposure times. Excessively deep anaesthesia can result in unacceptably compromised physiology, whilst excessively light anaesthesia can result in animals waking up. Here we report a respiratory monitoring setup for an in vivo bioluminescence and fluorescence imaging device which simultaneously allows real-time adaptive control of anaesthesia depth in multiple animals to (i) potentially increase the consistency between animals, (ii) ensure animals are maintained within minimally intrusive, adequate anaesthetic plane and (iii) provide a valuable refinement strategy for a common challenge within animal-based research.

Gemcitabine-Induced TIMP1 Attenuates Therapy Response and Promotes Tumor Growth and Liver Metastasis in Pancreatic Cancer.

Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in preclinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models. We identified potential pathways affected downstream of TIMP1 using the Illumina Human H12 array. Our findings were validated in both primary and metastatic models of pancreatic cancer. Gemcitabine increased inflammatory cytokines including TIMP1 in the KPC mouse model. TIMP1 was upregulated in patients with pancreatic intraepithelial neoplasias grade 3 and PDAC lesions relative to matched normal pancreatic tissue. In addition, TIMP1 played a role in tumor clonogenic survival and vascular density, while TIMP1 inhibition resensitized tumors to gemcitabine and radiotherapy. We observed a linear relationship between TIMP-1 expression, liver metastatic burden, and infiltration by CD11b+Gr1+ myeloid cells and CD4+CD25+FOXP3+ Tregs, whereas the presence of tumor cells was required for immune cell infiltration. Overall, our results identify TIMP1 upregulation as a resistance mechanism to gemcitabine and provide a rationale for combining chemo/radiotherapy with TIMP1 inhibitors in PDAC. Cancer Res; 77(21); 5952-62. ©2017 AACR.

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse.

INTRODUCTION: Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse. METHODS: A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours. RESULTS: The BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk. CONCLUSION: This is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.

Identification and genetic characterization of classical swine fever virus isolates in Brazil: a new subgenotype.

The classical swine fever (CSF) is a highly contagious viral disease of pigs and wild boar. The CSF causes great economic losses for pork production and the occurrence of the disease is notifiable to the OIE. The objective of this work was to identify and characterize CSF virus isolates from Brazil. Seven viral isolates were obtained and the full-length E2 sequences were analyzed. Phylogenetic analysis revealed a different segregation pattern between Brazilian isolates and members of subgenotype 1.1, forming a separate group within genotype 1. Genetic distance analysis suggested the existence of two new subgenotypes, designated subgenotypes 1.5 and 1.6.

An MRI-Compatible High Frequency AC Resistive Heating System for Homeothermic Maintenance in Small Animals.

PURPOSE: To develop an MRI-compatible resistive heater, using high frequency alternating current (AC), for temperature maintenance of anaesthetised animals. MATERIALS AND METHODS: An MRI-compatible resistive electrical heater was formed from narrow gauge wire connected to a high frequency (10-100 kHz) AC power source. Multiple gradient echo images covering a range of echo times, and pulse-acquire spectra were acquired with the wire heater powered using high frequency AC or DC power sources and without any current flowing in order to assess the sensitivity of the MRI acquisitions to the presence of current flow through the heater wire. The efficacy of temperature maintenance using the AC heater was assessed by measuring rectal temperature immediately following induction of general anaesthesia for a period of 30 minutes in three different mice. RESULTS: Images and spectra acquired in the presence and absence of 50-100 kHz AC through the wire heater were indistinguishable, whereas DC power created field shifts and lineshape distortions. Temperature lost during induction of anaesthesia was recovered within approximately 20 minutes and a stable temperature was reached as the mouse's temperature approached the set target. CONCLUSION: The AC-powered wire heater maintains adequate heat input to the animal to maintain body temperature, and does not compromise image quality.

Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.

Cancer cells can adapt and survive under low nutrient conditions, but underlying mechanisms remain poorly explored. We demonstrate here that glucose maintains a functional complex between the co-chaperone URI, PP1γ, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1γ release and URI-mediated OGT inhibition. Low OGT activity reduces O-GlcNAcylation and promotes c-MYC degradation to maintain cell survival. In the presence of glucose, PP1γ-bound URI increases OGT and c-MYC levels. Accordingly, mice expressing non-phosphorylatable URI (S371A) in hepatocytes exhibit high OGT activity and c-MYC stabilization, accelerating liver tumorigenesis in agreement with c-MYC oncogenic functions. Our work uncovers that URI-regulated OGT confers c-MYC-dependent survival functions in response to glucose fluctuations.