Imaging Techniques in Large Animals

Imaging techniques in large animals bridges the gap between preclinical and clinical research.  The same scanners can be used for large laboratory animals and for human beings and, with few  modifications, the same scanning protocols can also be used. Therefore, knowledge obtained from imaging  techniques in animal research can readily be used in humans. Similarly, medical hypotheses and problems  from clinical experience with humans can often be tested and studied in large animals. Imaging techniques  create either anatomical images (Computerized Tomography, CT or Magnetic Resonance Imaging, MRI) or  functional images of the body (Positron Emission Tomography, PET). While X-ray radiation is used to get  a cross-sectional CT image of the body, MRI involves the use of a magnetic field that forces the hydrogen  cellular nuclei to align in different positions. PET utilizes radiation emitted from the animal after injection  of radioactive tracers. The most commonly used large animals in imaging research are dogs, sheep, goats,  pigs and nonhuman primates. These laboratory animals have large organs and blood volumes that allow  repeated blood sampling, which is needed in most PET studies, while blood sampling is unnecessary for  CT and MRI imaging. Large animals are outbreed, and so many animals are typically needed in each study,  due to marked individual variation. That situation is unfavourable, because imaging studies of large animals  are expensive and time consuming. Except for nonhuman primates, large animals must be anaesthetised for  scanning procedures, and this may influence the experiments.

Exploring the link between the use of oral contraceptives and intrauterine devices, and alcohol consumption in young Danish women

Objective: This study aimed to identify potential differences in alcohol consumption and craving among users of combined oral contraceptives (COCs), intrauterine devices (IUDs), and naturally cycling (NC) women. Previous studies have often grouped COC and IUD users together, and so potentially overlooked behavioural differences between these two groups. Study design: We conducted a cross-sectional observational study, collecting data from 101 Danish women aged 20–30 through a web-based survey. Main outcome measures: Participants provided demographic information, details on use of hormonal contraceptives (HCs), menstrual history, and self-reported alcohol consumption. Additionally, the participants completed the Alcohol Use Disorders Identification Test (AUDIT) and the Alcohol Craving Questionnaire-Short Form-Revised (ACQ-SF-R). Results: All participants reported alcohol consumption and were well matched in age, body mass index (BMI), and education. A higher proportion of IUD users were smokers, but the difference in smoking rates among the groups were not statistically significant. One-way ANOVA revealed significant differences in alcohol consumption among the groups, with IUD users consuming more alcohol than NC women and COC users. No significant differences in alcohol consumption were found between NC women and COC users. While there were trends towards higher AUDIT and ACQ-SF-R scores among IUD users, these differences did not reach statistical significance across the groups. Conclusion: IUD users reported higher alcohol consumption than both COC users and NC women, while no substantial differences were observed between NC women and COC users. These findings provide valuable insights into the correlation between contraceptive methods and alcohol use. Although causality cannot be inferred, the results may aid healthcare professionals in developing tailored counselling strategies and identifying women who may be at increased risk of alcohol abuse.</p

Carbon dioxide dynamics in an agricultural headwater stream driven by hydrology and primary production

Headwater streams are known to be hotspots for carbon dioxide (CO2) emissions to the atmosphere and are hence important components in landscape carbon balances. However, surprisingly little is known about stream CO2 dynamics and emissions in agricultural settings, a land use type that globally covers ca. 40% of the continental area. Here we present hourly measured in situ stream CO2 concentration data from a 11.3 km(2) temperate agricultural headwater catchment covering more than 1 year (in total 339 d excluding periods of ice and snow cover). The stream CO2 concentrations during the entire study period were generally high (median 3.44 mg C L-1, corresponding to partial pressures (pCO(2)) of 4778 mu atm) but were also highly variable (IQR = 3.26 mgC L-1). The CO2 concentration dynamics covered a variety of different timescales from seasonal to hourly, with an interplay of hydrological and biological controls. The hydrological control was strong (although with both positive and negative influences dependent on season), and CO2 concentrations changed rapidly in response to rainfall and snowmelt events. However, during growing-season base flow and receding flow conditions, aquatic primary production seemed to control the stream CO2 dynamics, resulting in elevated diel patterns. During the dry summer period, rapid rewetting following precipitation events generated high CO2 pulses exceeding the overall median level of stream CO2 (up to 3 times higher) observed during the whole study period. This finding highlights the importance of stream intermittency and its effect on stream CO2 dynamics. Given the observed high levels of CO2 and its temporally variable nature, agricultural streams clearly need more attention in order to understand and incorporate these considerable dynamics in large-scale extrapolations

Modelling impacts of atmospheric deposition and temperature on long-term DOC trends

It is increasingly recognised that widespread and substantial increases in Dissolved organic carbon (DOC) concentrations in remote surface, and soil, waters in recent decades are linked to declining acid deposition. Effects of rising pH and declining ionic strength on DOC solubility have been proposed as potential dominant mechanisms. However, since DOC in these systems is derived mainly from recently-fixed carbon, and since organic matter decomposition rates are considered sensitive to temperature, uncertainty persists over the extent to which other drivers that could influence DOC production. Such potential drivers include fertilization by nitrogen (N) and global warming. We therefore ran the dynamic soil chemistry model MADOC for a range of UK soils, for which time series data are available, to consider the likely relative importance of decreased deposition of sulphate and chloride, accumulation of reactive N, and higher temperatures, on soil DOC production in different soils. Modelled patterns of DOC change generally agreed favourably with measurements collated over 10-20 years, but differed markedly between sites. While the acidifying effect of sulphur deposition appeared to be the predominant control on the observed soil water DOC trends in all the soils considered other than a blanket peat, the model suggested that over the long term, the effects of nitrogen deposition on N-limited soils may have been sufficient to raise the “acid recovery DOC baseline” significantly. In contrast, reductions in non-marine chloride deposition and effects of long term warming appeared to have been relatively unimportant. The suggestion that future DOC concentrations might exceed preindustrial levels as a consequence of nitrogen pollution has important implications for drinking water catchment management and the setting and pursuit of appropriate restoration targets, but findings still require validation from reliable centennial-scale proxy records, such as those being developed using palaeolimnological techniques

Effects of mindfulness-based stress reduction on neuropeptide Y plasma levels in stressed individuals

BACKGROUND: Clinical studies have suggested that dysregulation of the neuropeptide Y (NPY) system may play a role in psychiatric disorders, including chronic stress. Meanwhile, Mindfulness Based Stress Reduction (MBSR) has shown promise for stress-related maladies. However, no studies have explored whether MBSR can change plasma NPY concentration in stressed individuals.METHOD: Individuals with symptoms of chronic stress were randomly assigned to eight weeks of either MBSR (n = 15), a locally-developed stress reduction intervention (LSR) (n = 15) or a wait-list control group (n = 20). Blood samples were collected at baseline and at a twelve-week follow-up to determine the effects of MBSR or LSR compared to the wait-list control group on NPY levels.RESULTS: The MBSR group had increased plasma NPY levels after the program compared to the waitlist control group, whereas the LSR group was not statistically different from the other groups.CONCLUSION: This pilot study provides evidence of the feasibility of MBSR to alter plasma NPY.</p

Sucrose intake lowers mu-opioid and dopamine D2/3 receptor availability in porcine brain

Excessive sucrose consumption elicits addiction-like craving that may underpin the obesity epidemic. Opioids and dopamine mediate the rewarding effects of drugs of abuse, and of natural rewards from stimuli such as palatable food. We investigated the effects of sucrose using PET imaging with [11C]carfentanil (μ-opioid receptor agonist) and [11C]raclopride (dopamine D2/3 receptor antagonist) in seven female anesthetized Göttingen minipigs. We then gave minipigs access to sucrose solution for one hour on 12 consecutive days and performed imaging again 24 hours after the final sucrose access. In a smaller sample of five minipigs, we performed an additional [11C]carfentanil PET session after the first sucrose exposure. We calculated voxel-wise binding potentials (BPND) using the cerebellum as a region of non-displaceable binding, analyzed differences with statistical non-parametric mapping, and performed a regional analysis. After 12 days of sucrose access, BPND of both tracers had declined significantly in striatum, nucleus accumbens, thalamus, amygdala, cingulate cortex and prefrontal cortex, consistent with down-regulation of receptor densities. After a single exposure to sucrose, we found decreased binding of [11C]carfentanil in nucleus accumbens and cingulate cortex, consistent with opioid release. The lower availability of opioid and dopamine receptors may explain the addictive potential associated with intake of sucrose.</p

18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis

BACKGROUND: Arterial 18fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered a measure of atherosclerotic plaque macrophages and is used for quantification of disease activity in clinical trials, but the distribution profile of FDG across macrophages and other arterial cells has not been fully clarified. OBJECTIVES: The purpose of this study was to analyze FDG uptake in different arterial tissues and their contribution to PET signal in normal and atherosclerotic arteries. METHODS: Wild-type and D374Y-PCSK9 transgenic Yucatan minipigs were fed a high-fat, high-cholesterol diet to induce atherosclerosis and subjected to a clinical FDG-PET and computed tomography scan protocol. Volumes of arterial media, intima/lesion, macrophage-rich, and hypoxic tissues were measured in serial histological sections. Distributions of FDG in macrophages and other arterial tissues were quantified using modeling of the in vivo PET signal. In separate transgenic minipigs, the intra-arterial localization of FDG was determined directly by autoradiography. RESULTS: Arterial FDG-PET signal appearance and intensity were similar to human imaging. The modeling approach showed high accuracy in describing the FDG-PET signal and revealed comparable FDG accumulation in macrophages and other arterial tissues, including medial smooth muscle cells. These findings were verified directly by autoradiography of normal and atherosclerotic arteries. CONCLUSIONS: FDG is taken up comparably in macrophage-rich and -poor arterial tissues in minipigs. This offers a mechanistic explanation to a growing number of observations in clinical imaging studies that have been difficult to reconcile with macrophage-selective FDG uptake.This study was supported by the Danish Council for Independent Research/Medical Sciences, Lundbeck Foundation, Danish Heart Foundation, and Aarhus University Research Foundation (AU IDEAS). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation; and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Bentzon has served as a consultant for Novo Nordisk A/S; and has within the last 5 years received an investigator-initiated preclinical research grant from Regeneron PharmaceuticalsS

Aquatic export of young dissolved and gaseous carbon from a pristine boreal fen: Implications for peat carbon stock stability

The stability of northern peatland's carbon (C) store under changing climate is of major concern for the global C cycle. The aquatic export of C from boreal peatlands is recognized as both a critical pathway for the remobilization of peat C stocks as well as a major component of the net ecosystem C balance (NECB). Here, we present a full year characterization of radiocarbon content (14C) of dissolved organic carbon (DOC), carbon dioxide (CO2), and methane (CH4) exported from a boreal peatland catchment coupled with 14C characterization of the catchment's peat profile of the same C species. The age of aquatic C in runoff varied little throughout the year and appeared to be sustained by recently fixed C from the atmosphere (&lt;60 years), despite stream DOC, CO2, and CH4 primarily being sourced from deep peat horizons (2&ndash;4 m) near the mire's outlet. In fact, the 14C content of DOC, CO2, and CH4 across the entire peat profile was considerably enriched with postbomb C compared with the solid peat material. Overall, our results demonstrate little to no mobilization of ancient C stocks from this boreal peatland and a relatively large resilience of the source of aquatic C export to forecasted hydroclimatic changes