Whole-body Level Research Articles

The Modulatory Effects and Therapeutic Potential of Cannabidiol in the Gut.

Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that exists in the Cannabis sativa plant. CBD has been found to act on various receptors, including both cannabinoid and non-cannabinoid receptors. In addition, CBD has antioxidant effects that are independent of receptors. CBD has demonstrated modulatory effects at different organ systems, such as the central nervous system, immune system, and the gastrointestinal system. Due to its broad effects within the body and its safety profile, CBD has become a topic of therapeutic interest. This literature review summarizes previous research findings with regard to the effect of CBD on the gastrointestinal (GI) system, including its effects at the molecular, cellular, organ, and whole-body levels. Both pre-clinical animal studies and human clinical trials are reviewed. The results of the studies included in this literature review suggest that CBD has significant impact on intestinal permeability, the microbiome, immune cells and cytokines. As a result, CBD has been shown to have therapeutic potential for GI disorders such as inflammatory bowel disease (IBD). Furthermore, through interactions with the gut, CBD may also be helpful in the treatment of disorders outside the GI system, such as non-alcoholic liver disease, postmenopausal disorders, epilepsy, and multiple sclerosis. In the future, more mechanistic studies are warranted to elucidate the detailed mechanisms of action of CBD in the gut. In addition, more well-designed clinical trials are needed to explore the full therapeutic potential of CBD on and through the gut.

Studies on the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue

Purpose To investigate the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue and whole-body inflammation levels. Material and methods Forty-two C57BL/6J mice were randomly divided into the control group, the 1, 3, and 7 days after 2 Gy irradiation group, and the 1, 3, and 7 days after 4 Gy irradiation group, with six mice in each group. The histopathology, cellular senescence, oxidative-antioxidant, DNA damage repair, and inflammation-related indicators of irradiated mice were examined. Results Compared with the control group, the histopathological scores, the positive area of senescence-associated-β-galactosidase (SA-β-Gal) staining, and the mRNA levels of senescence-related genes in the lung tissues in all dose groups increased on 1, 3, and 7 days after irradiation. In peripheral blood, erythrocytes, leukocytes, platelets, hemoglobin, 8-hydroxydeoxyguanosine (8-OHdG), C-reactive protein, and other indicators showed a different trend in all dose groups. The levels of malondialdehyde(MDA), superoxide dismutase (SOD), glutathione (GSH), and 8-OHdG in the lung tissue showed different trends after 2 Gy and 4 Gy irradiation. The 8-Oxoguanine DNA glycosylase 1 (hOGG1) and O-6-methylguanine-DNA methyltransferase (MGMT) mRNA levels showed a trend of increasing and then decreasing. The levels of whole-body inflammation were significantly correlated with the levels of indicators related to cellular senescence and damage repair in the lung tissue of mice. Conclusions The moderate doses of ionizing radiation induce oxidative stress, and DNA damage and increase DNA repair gene expression in mouse lung tissue. The lung tissue cellular senescence correlates with the level of whole-body inflammation.

Potential Effects of Lifelong Team Handball and Football Training and Nutritional Habits on Bone Health and Body Composition in Elderly Women.

The aim of this study was to evaluate the effects of lifelong team handball/football training on regional bone health and body composition in elderly women. Seventeen elderly women team handball/football players (65.9 ± 5.7 years) and twenty-one untrained age-matched women (controls) (67.7 ± 5.1 years) participated. Whole-body and regional dual-energy X-ray absorptiometry scans of arms, legs, and lower spine (L1-L4) were performed. We observed 8% and 9% higher bone mineral density (BMD) and bone mineral content (BMC), respectively, at the whole-body level and in the legs and 11.5% higher BMC in the legs in team handball/football players compared to untrained age-matched controls (p < 0.05). Higher total and leg lean body mass (p < 0.05), along with lower total body fat percentage (p < 0.05) and higher T- and Z-scores, markers of fragility risk fracture (0.294 ± 1.461 vs. -0.538 ± 1.031; 1.447 ± 1.278 vs. 0.724 ± 0.823, respectively), were also found in team handball/football players compared to controls (p < 0.05). No significant differences in nutritional habits were observed between groups. Our study suggest that the beneficial effects of lifetime handball/football practice on bone preservation in elderly women occur independently from nutritional intake, which emphasize the potential role of team sports in osteoporosis prevention. Future studies should focus on the cofounding factors and causative mechanisms mediated by team sport practice in osteoporosis prevention.

Acute waterborne cadmium exposure induces liver ferroptosis in Channa argus

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe2+, ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

On the pathogenesis of obesity: causal models and missing pieces of the puzzle.

Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century. Here, we summarize outcomes of a recent workshop in Copenhagen that brought together obesity experts from around the world to discuss causal models of obesity pathogenesis. These discussions helped to operationally define commonly used terms; delineate the structure of each model, particularly focussing on areas of overlap and divergence; challenge ideas about the importance of purported causal factors for weight gain; and brainstorm on the key scientific questions that need to be answered. We hope that more experimental research in nutrition and other related fields, and more testing of the models and their predictions will pave the way and provide more answers about the pathogenesis of obesity than those currently available.

The effects of four hours of normobaric hypoxia on the vestibular control of balance.

Whole-body vestibular-evoked balance responses decrease following ~ 55min of normobaric hypoxia. It is unclear how longer durations of hypoxia affect the vestibular control of balance at the muscle and whole-body levels. This study examined how four hours of normobaric hypoxia influenced the vestibular control of balance. Fifteen participants (4 females; 11 males) stood on a force plate with vision occluded and head rotated rightward while subjected to three blocks of binaural, bipolar stochastic electrical vestibular stimulation (EVS; 0-25Hz, root mean square amplitude = 1.1mA) consisting of two, 90-s trials. The relationship between EVS and anteroposterior (AP) forces or medial gastrocnemius (MG) electromyography (EMG) was estimated in the time and frequency domains at baseline (BL; 0.21 fraction of inspired oxygen-FIO2) and following two (H2) and four (H4) hours of normobaric hypoxia (0.11 FIO2). The EVS-MG EMG short-latency peak and peak-to-peak amplitudes were smaller than BL at H2 and H4, but the medium-latency peak amplitude was only lower at H4. The EVS-AP force medium-latency peak amplitude was lower than BL at H4, but the short-latency peak and peak-to-amplitudes were unchanged. The EVS-MG EMG coherence and gain were reduced compared to BL at H2 and H4 across multiple frequencies ≥ 7Hz, whereas EVS-AP force coherence was blunted at H4 (≤ 4Hz), but gain was unaffected. Overall, the central nervous system's response to vestibular-driven signals during quiet standing wasdecreased forup to four hours of normobaric hypoxia, and vestibular-evoked responses recorded within postural muscles may be more sensitive than the whole-body response.

A mechanism for slow rhythms in coordinated pancreatic islet activity

Insulin levels in the blood oscillate with a variety of periods, including rapid (5–10 min), ultradian (50–120 min), and circadian (24 h). Oscillations of insulin are beneficial for lowering blood glucose and disrupted rhythms are found in people with type 2 diabetes and their close relatives. These in vivo secretion dynamics imply that the oscillatory activity of individual islets of Langerhans are synchronized, although the mechanism for this is not known. One mechanism by which islets may synchronize is negative feedback of insulin on whole-body glucose levels. In previous work, we demonstrated that a negative feedback loop with a small time delay, to account for the time required for islets to be exposed to a new glucose concentration in vivo, results in small 3–6 islet populations synchronizing to produce fast closed-loop oscillations. However, these same islet populations could also produce slow closed-loop oscillations with periods longer than the natural islet oscillation periods. Here, we investigate the origin of the slow oscillations and the bistability with the fast oscillations using larger islet populations (20–50 islets). In contrast to what was observed earlier, larger islet populations mainly synchronize to longer-period oscillations that are approximately twice the delay time used in the feedback loop. A mean-field model was also used as a proxy for a large islet population to uncover the underlying mechanism for the slow rhythm. The heterogeneous intrinsic oscillation periods of the islets interferes with this rhythm mechanism when islet populations are small, and is similar to adding noise to the mean-field model. Thus, the effect of a time delay in the glucose feedback mechanism is similar to other examples of time-delayed systems in biology and may be a viable mechanism for ultradian oscillations.

Accuracy tradeoffs between individual bone and joint-level statistical shape models of knee morphology

Statistical shape models (SSMs) are useful tools in evaluating variation in bony anatomy to assess pathology, plan surgical interventions, and inform the design of orthopaedic implants and instrumentation. Recently, by considering multiple bones spanning a joint or the whole lower extremity, SSMs can support studies investigating articular conformity and joint mechanics. The objective of this study was to assess tradeoffs in accuracy between SSMs of the femur or tibia individually versus a combined joint-level model. Three statistical shape models were developed (femur-only, tibia-only, and joint-level) for a training set of 179 total knee arthroplasty (TKA) patients with osteoarthritis representing both genders and several ethnicities. Bone geometries were segmented from preoperative CT scans, meshed with triangular elements, and registered to a template for each SSM. Principal component analysis was performed to determine modes of variation. The statistical shape models were compared using measures of compactness, accuracy, generalization, and specificity. The generalization evaluation, assessing the ability to describe an unseen instance in a leave-one-out analysis, showed that errors were consistently smaller for the individual femur and tibia SSMs than for the joint-level model. However, when additional modes were included in the joint-level model, the errors were comparable to the individual bone results, with minimal additional computational expense. When developing more complex SSMs at the joint, lower limb, or whole-body level, the use of an error threshold to inform the number of included modes, instead of 95 % of the variation explained, can help to ensure accurate representations of anatomy.

Modelling changes in whole body and fillet fatty acid composition of Atlantic salmon with changing levels of dietary omega-3 intake

In this study, a fatty acid dilution model was coupled with a dynamic nutrient demand model to provide an integrated model capable of predicting the whole-body and fillet lipid and fatty acid levels of Atlantic salmon (Salmo salar) following a change in dietary fatty acid profile. Based on knowledge of the initial fish and dietary fatty acid compositions, diet digestible energy density, the water temperature and duration of feeding, the model demonstrated that it was possible to predict a range of parameters, including the growth, feed utilisation, whole-body and fillet (Norwegian Quality Cut; NQC) total lipid, and fatty acid levels of the fish. The model was validated against five separate experiments, including two farm-based trials with harvest size fish. Validation experiments involved fish ranging in size (initial weights to final weights) from 138 g/fish to 5138 g/fish and running for durations of between 66 and 323 days. For the laboratory experiments, prediction of growth, feed utilisation and fatty acid deposition proved to be highly predictable (R2 > 0.998). Fatty acid profiles from both short and long-term cage trials were also highly predictable. Despite the reduced level of weight change in the short-term cage trial, and the higher variability that was observed in growth performance, the fatty acid deposition still showed high levels of correlation (R2 > 0.996), between the modelled and measured fatty acid levels in the fish fillet. Departure from linearity was more evident in the long-term cage trial, but correlation still exceeded R2 > 0.995 for all treatments. Prediction of whole-body and NQC total lipid levels was less accurate, with correlations being R2 = 0.962 and R2 = 0.909 respectively. Model outputs were generally more accurate with greater weight change and/or experiment duration. The outcome of this study shows that the model developed here provides a useful tool for the estimation of the fatty acid composition of Atlantic salmon following a change in dietary fatty acid composition. This could help assist in the more judicious use of dietary long-chain omega-3 fatty acids for commercial salmon farming.

Intergenerational Impact of Parental Zinc Deficiency on Metabolic and Redox Outcomes in Drosophila melanogaster.

Zinc deficiency is a common nutritional disorder with detrimental health consequences. Whether parental zinc deficiency induces intergenerational effects remains largely unknown. We investigated the effects of a combined maternal and paternal zinc deficiency on offspring's metabolic outcomes and gene expression changes in Drosophila melanogaster. The parent flies were raised on zinc-deficient diets throughout development, and their progeny were assessed. Offspring from zinc-deprived parents exhibited a significant (p < 0.05) increase in body weight and whole-body zinc levels. They also displayed disrupted glucose metabolism, altered lipid homeostasis, and diminished activity of antioxidant enzymes. Gene expression analysis revealed significant (p < 0.05) alterations in zinc transport genes, with increases in mRNA levels of dZIP1 and dZnT1 for female and male offspring, respectively. Both sexes exhibited reduced dZnT35C mRNA levels and significant (p < 0.05) increases in the mRNA levels of DILP2 and proinflammatory markers, Eiger and UPD2. Overall, female offspring showed higher sensitivity to parental zinc deficiency. Our findings underscore zinc's crucial role in maintaining health and the gender-specific responses to zinc deficiency. There is the need for further exploration of the underlying mechanisms behind these intergenerational effects.

Time-course atherogenic blood lipid response to statin discontinuation in dyslipidemic adults

Background and aimsHalf of dyslipidemic patients sometimes discontinue statin medication. It is unclear if blood atherogenic risk increases right after statin discontinuation or if there is a lingering protective effect. We sought to determine if a legacy effect prevented blood lipid increases during the first stages of statin cessation. Methods and resultsAtherogenic blood lipid profile was measured in 10 overweight (BMI 31 ± 3 kg m−2) middle-aged males (62 ± 7 years old), statin users, while fasted and postprandially. Trials were conducted before (i.e., Day 0) and after 4, 7, 15, and 30 days of statin withdrawal and 20 days after statins reloading (Day 50).Four days after statin discontinuation, blood fasting LDL-c, total cholesterol (CHOL), and triglyceride (TG) concentrations increased by 30%, 18%, and 17%, respectively (P < 0.05). The increases in LDL-c, CHOL, and TG peaked after 7–15 days at 79%, 48%, and 34% of basal levels (P < 0.001), respectively. There were no significant correlations between the increases in blood lipids and the dose or years under statin treatment (P = 0.156–0.575). Twenty days after resuming statins, blood LDL-c (2.79 ± 1.06 vs 2.20 ± 0.50 mmol L−1; P = 0.568), CHOL (4.85 ± 1.41 vs 4.25 ± 0.83 mmol L−1; P = 0.747), and TG (1.47 ± 0.60 vs 1.50 ± 0.68 mmol L−1; P = 0.782), returned to basal levels. ConclusionsOur data does not support a statin lingering/legacy effect in blood lipids since they dangerously increased after only 4 days of statin withdrawal in every patient, regardless of dose and years under treatment. Reloading statins restored blood lipids, evidencing a reproducible biological effect at the whole-body level.

The impact of GLP-1 signalling on the energy metabolism of pancreatic islet β-cells and extrapancreatic tissues

Glucagon-like peptide-1 signalling impacts glucose homeostasis and appetite thereby indirectly affecting substrate availability at the whole-body level. The incretin canonically produces an insulinotropic effect, thereby lowering blood glucose levels by promoting the uptake and inhibiting the production of the sugar by peripheral tissues. Likewise, GLP-1 signalling within the central nervous system reduces the appetite and food intake, whereas its gastric effect delays the absorption of nutrients, thus improving glycaemic control and reducing the risk of postprandial hyperglycaemia. We review the molecular aspects of the GLP-1 signalling, focusing on its impact on intracellular energy metabolism. Whilst the incretin exerts its effects predominantly via a Gs receptor, which decodes the incretin signal into the elevation of intracellular cAMP levels, the downstream signalling cascades within the cell, acting on fast and slow timescales, resulting in an enhancement or an attenuation of glucose catabolism, respectively.

Inhibitor Properties of Rue (Ruta graveolens L.) on Spermatogenesis in Guppy Poecilia reticulata Peters, 1859

This study was conducted to investigate the effect of Rue (RE), a medicinal herb having anti-androgenic characteristic on the sexuality of guppy males. In total, 120 males were selected randomly, acclimated and divided equally into four groups that received the RE ethanolic extract at 0, 1, 10 and 100 mg.kg-1, respectively for 30 days. The findings revealed that 100 mg.kg-1 had significantly lower whole-body testosterone levels than control. Furthermore, males administered RE at all doses had a significantly lower gonopodial index than the control group. Whereas, administration of RE at 10 and 100 mg.kg-1 causes a lowering in sperm counts than the control group. Regarding with histopathological examination, the testes of control males were well-differentiated with an increase in spermatozeugmata proportion at all spermatogenesis stages with a significant proportion of cystic structures containing spermatozoa. On the other hand, RE-fed animals showed a dose-dependent decrease in spermatozeugmata and an increase in spermatocytes' number of ducts, indicating the role of RE in reducing the development of guppy’s spermatogenesis. In conclusion, Rue can impact the sexual parameters of adult guppy males by confirming the anti-androgenic properties of RE.

Preliminary evidence of localizing CD8+ T-cell responses in COVID-19 patients with PET imaging.

The upper respiratory tract (URT) is the entry site for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), from where it further disseminates. Early and effective adaptive immune responses are crucial to restrict viral replication and limit symptom development and transmission. Current vaccines increasingly incorporate strategies to boost mucosal immunity in the respiratory tract. Positron emission tomography (PET) is a non-invasive technology that measures cellular responses at a whole-body level. In this case series, we explored the feasibility of [89Zr]Zr-crefmirlimab berdoxam PET to assess CD8+ T-cell localization during active COVID-19. Our results suggest that CD8+ T-cell distributions assessed by PET imaging reflect their differentiation and functional state in blood. Therefore, PET imaging may represent a novel tool to visualize and quantify cellular immune responses during infections at a whole-body level.

13C-Stable isotope resolved metabolomics uncovers dynamic biochemical landscape of gut microbiome-host organ communications in mice

BackgroundGut microbiome metabolites are important modulators of host health and disease. However, the overall metabolic potential of the gut microbiome and interactions with the host organs have been underexplored.ResultsUsing stable isotope resolved metabolomics (SIRM) in mice orally gavaged with 13C-inulin (a tracer), we first observed dynamic enrichment of 13C-metabolites in cecum contents in the amino acids and short-chain fatty acid metabolism pathways. 13C labeled metabolites were subsequently profiled comparatively in plasma, liver, brain, and skeletal muscle collected at 6, 12, and 24 h after the tracer administration. Organ-specific and time-dependent 13C metabolite enrichments were observed. Carbons from the gut microbiome were preferably incorporated into choline metabolism and the glutamine-glutamate/GABA cycle in the liver and brain, respectively. A sex difference in 13C-lactate enrichment was observed in skeletal muscle, which highlights the sex effect on the interplay between gut microbiome and host organs. Choline was identified as an interorgan metabolite derived from the gut microbiome and fed the lipogenesis of phosphatidylcholine and lysophosphatidylcholine in host organs. In vitro and in silico studies revealed the de novo synthesis of choline in the human gut microbiome via the ethanolamine pathway, and Enterococcus faecalis was identified as a major choline synthesis species. These results revealed a previously underappreciated role for gut microorganisms in choline biosynthesis.ConclusionsMulticompartmental SIRM analyses provided new insights into the current understanding of dynamic interorgan metabolite transport between the gut microbiome and host at the whole-body level in mice. Moreover, this study singled out microbiota-derived metabolites that are potentially involved in the gut-liver, gut-brain, and gut-skeletal muscle axes.1fG1mJvQp124HCbb2HZFdqVideo

Sedentary behavior in mice induces metabolic inflexibility by suppressing skeletal muscle pyruvate metabolism.

Carbohydrates and lipids provide the majority of substrates to fuel mitochondrial oxidative phosphorylation. Metabolic inflexibility, defined as an impaired ability to switch between these fuels, is implicated in a number of metabolic diseases. Here, we explore the mechanism by which physical inactivity promotes metabolic inflexibility in skeletal muscle. We developed a mouse model of sedentariness, small mouse cage (SMC), that, unlike other classic models of disuse in mice, faithfully recapitulated metabolic responses that occur in humans. Bioenergetic phenotyping of skeletal muscle mitochondria displayed metabolic inflexibility induced by physical inactivity, demonstrated by a reduction in pyruvate-stimulated respiration (JO2) in the absence of a change in palmitate-stimulated JO2. Pyruvate resistance in these mitochondria was likely driven by a decrease in phosphatidylethanolamine (PE) abundance in the mitochondrial membrane. Reduction in mitochondrial PE by heterozygous deletion of phosphatidylserine decarboxylase (PSD) was sufficient to induce metabolic inflexibility measured at the whole-body level, as well as at the level of skeletal muscle mitochondria. Low mitochondrial PE in C2C12 myotubes was sufficient to increase glucose flux toward lactate. We further implicate that resistance to pyruvate metabolism is due to attenuated mitochondrial entry via mitochondrial pyruvate carrier (MPC). These findings suggest a mechanism by which mitochondrial PE directly regulates MPC activity to modulate metabolic flexibility in mice.

The role of phenotypic plasticity and corticosterone in coping with pond drying conditions in yellow-bellied toad (Bombina variegata, Linnaeus 1758) tadpoles.

Amphibian larvae inhabiting temporary ponds often exhibit the capacity to accelerate development and undergo metamorphosis in challenging conditions like desiccation. However, not all species exhibit this ability, the yellow-bellied toad (Bombina variegata) is one such example. The underlying mechanisms behind the inability to accelerate development under desiccation remain largely unexplored. The hypothalamic-pituitary-interrenal (HPI) axis and corticosterone (CORT), which act synergistically with thyroid hormone, are thought to facilitate metamorphosis in response to desiccation stress. In this study, we aimed to investigate whether modification in the HPI axis, particularly CORT levels, contributes to the absence of adaptive plasticity in B. variegata under desiccation stress. The study design included four treatments: high water level, high water level with exogenous CORT, low water level, and low water level with metyrapone (a CORT synthesis inhibitor). The main objective was to evaluate the effects of these treatments on whole-body corticosterone levels, life history, morphological traits, and oxidative stress parameters during the prometamorphic and metamorphic climax developmental stages. While low water level had no effect on total corticosterone levels, larval period, body condition index, and metamorphic body shape, it negatively affected metamorph size, mass, and growth rate. Our findings suggest that constant exposure to desiccation stress over generations may have led to modifications in the HPI axis activity in B. variegata, resulting in adaptation to changes in water level, evident through the absence of stress response. Consequently, CORT may not be a relevant stress indicator in desiccation conditions for this species.

Thyroid and sex hormone disrupting effects of DEHTP at different life stages of zebrafish (Danio rerio)

Di(2-ethylhexyl) terephthalate (DEHTP) is an alternative plasticizer widely used in numerous consumer products, replacing di(2-ethylhexyl) phthalate (DEHP). Hence, DEHTP has been frequently detected in the environment and humans. As a structural isomer and functional analog of DEHP, DEHTP is a suspected endocrine disruptor. Here, we evaluated thyroid-disrupting effects of DEHTP using embryo-larval and adult male zebrafish. We also investigated its sex hormone disruption potential in the adult zebrafish. After 5- and 7-days of exposure to DEHTP, significant increases in whole-body thyroid hormonal levels were observed in the larval fish. Down-regulation of several thyroid-regulating genes, including trh, tshβ, nis, and dio2, was observed, but only after 5-day exposure. Following a 21-day exposure, the adult male zebrafish exhibited a significant decrease in total triiodothyronine and an increase in thyroid-stimulating hormones. Potential changes in the deiodination of thyroid hormones, supported by the up-regulation of two deiodinases, dio1 and dio3a, along with the down-regulation of dio2, could explain the thyroid hormone changes in the adult zebrafish. Moreover, significant trends of decrease in estradiol and 11-ketotestosterone, along with increase of testosterone (T), were observed in the adult zebrafish. Up-regulation of several steroidogenic genes may explain elevated T, while exact mechanisms of action warrant further investigation. Our results demonstrate that DEHTP can cause disruptions of thyroid and sex hormones at different life stages in zebrafish.

Advances in body composition: a 100-year journey.

Knowledge of human body composition at the dawn of the twentieth century was based largely on cadaver studies and chemical analyses of isolated organs and tissues. Matters soon changed by the nineteen twenties when the Czech anthropologist Jindřich Matiegka introduced an influential new anthropometric method of fractionating body mass into subcutaneous adipose tissue and other major body components. Today, one century later, investigators can not only quantify every major body component in vivo at the atomic, molecular, cellular, tissue-organ, and whole-body organizational levels, but go far beyond to organ and tissue-specific composition and metabolite estimates. These advances are leading to an improved understanding of adiposity structure-function relations, discovery of new obesity phenotypes, and a mechanistic basis of some weight-related pathophysiological processes and adverse clinical outcomes. What factors over the past one hundred years combined to generate these profound new body composition measurement capabilities in living humans? This perspective tracks the origins of these scientific innovations with the aim of providing insights on current methodology gaps and future research needs.

Do Paralympic athletes suffer from brittle bones? Prevalence and risk factors of low bone mineral density in Paralympic athletes

BackgroundBone health may be a concern in Paralympic athletes, given the presence of multiple risk factors predisposing these athletes to low bone mineral density (BMD). Objective: We aimed to assess the prevalence of low BMD among Paralympic athletes participating in various sport disciplines, and to identify potential risk factors for low BMD. MethodsSeventy Paralympic athletes, of whom 51 % were wheelchair-dependent, were included in this cross-sectional study. BMD of the whole-body, lumbar spine, total hip, and femoral neck were assessed by dual-energy x-ray absorptiometry. Comparisons between groups were conducted by one-way ANOVA, and regression analyses were conducted to identify potential risk factors for low BMD. ResultsThe prevalence of low BMD (Z-score < −1.0) was highest at femoral neck (34 %), followed by total hip (31 %), whole-body (21 %), and lumbar spine (18 %). Wheelchair-dependent athletes had significantly lower BMD Z-scores compared to the non-wheelchair-dependent athletes at whole-body level (−0.5 ± 1.4 vs 0.2 ± 1.3; P = 0.04), total hip (−1.1 ± 1.2 vs 0.0 ± 1.1; P < 0.01), and femoral neck (−1.0 ± 1.3 vs −0.1 ± 1.2; P < 0.01). At the lumbar spine, low BMD was completely absent in wheelchair basketball and tennis players. Regression analyses identified body mass, wheelchair dependence, and type of sport, as the main risk factors for low BMD. ConclusionsIn this cohort of Paralympic athletes, low BMD is mainly present at the hip, and to a lesser extent at the whole-body and lumbar spine. The most prominent risk factors for low BMD in Paralympic athletes are related to mechanical loading patterns, including wheelchair use, the type of sport, and body mass.