Irisin Treatment during Chronic Inflammatory Bowel Disease in an Rodent Model Improves Bone Formation Rate

Bone is a dynamic tissue that responds to many stressors including physical stress and certain disease states. Chronic systemic inflammatory conditions, like inflammatory bowel disease (IBD), result in increased bone resorption and decreased bone formation leading to low bone mass and high fracture incidence. There currently are no effective, safe treatments for IBD. Irisin is a hormone that is released during exercise and has previously been shown to increase bone mass. PURPOSE: Determine if exogenous treatment with irisin can mitigate the inflammatory insult of chronic IBD on bone. We hypothesized that young male rats with induced IBD and treatment with exogenous irisin would have increased bone formation rate (BFR) and mitigated loss of bone mineral density compared to rats with only IBD. METHOD: Male Sprague Dawley rats (2 months) were divided into four groups: controls (CON), those given dextran sodium sulfate in drinking water to induce IBD (DSS), CON rats given exogenous irisin (CON+IR), and DSS rats given exogenous irisin (DSS+IR). n per group=8.. Irisin injections began one week after initiation of IBD for the remainder of the four week protocol. RESULTS: Peripheral quantitative computed tomography (pQCT) of the proximal tibia metaphysis showed a significant decrease in total bone mineral content and volumetric bone mineral density (cortical shell+cancellous core) in both DSS groups compared to both control groups. Dynamic histomorphomery revealed higher cancellous BFR due to irisin treatment in both CON and DSS rats resulting in DSS+IR having higher BFR than DSS. This was due largely to increases in mineralized surface indicating increased numbers of osteoblast teams. At the midshaft tibia, BFR was higher in DSS+IR, but not significantly different than DSS alone. This change was due more to increases in mineral apposition rate indicating higher activity of osteoblast teams. CONCLUSION: In this study, we demonstrated that rats with DSS have low bone mass similar to patients with IBD. Although irisin did not mitigate this bone loss, our data indicates over time it would likely lead to improved bone mass due to increases in bone formation. Additionally, our data indicate greater improvements in BFR in the cancellous bone, a more active bone compartment, than the midshaft tibia, but slight increases in mineral apposition rate at this site demonstrate improved osteoblast activity due to irisin. Since IBD is a chronic, life-long disease, our data highlights the potential benefit of exogenous irisin treatment as well as exercise therapy for patients with IBD

Effects of Sex and Gender on Adaptation to Space: Musculoskeletal Health

There is considerable variability among individuals in musculoskeletal response to long-duration spaceflight. The specific origin of the individual variability is unknown but is almost certainly influenced by the details of other mission conditions such as individual differences in exercise countermeasures, particularly intensity of exercise, dietary intake, medication use, stress, sleep, psychological profiles, and actual mission task demands. In addition to variations in mission conditions, genetic differences may account for some aspect of individual variability. Generally, this individual variability exceeds the variability between sexes that adds to the complexity of understanding sex differences alone. Research specifically related to sex differences of the musculoskeletal system during unloading is presented and discussed

Health Sciences Libraries

Health sciences librarians serve as uniquely trained reference librarians who specialize in the research and dissemination of medical and health information and are an important link to quality health information for patients and consumers. The authors describe how the landscape of health sciences librarianship is constantly changing as new technology emerges, along with librarians\u27 roles within the healthcare system

Automating the assessment of biofouling in images using expert agreement as a gold standard

Biofouling is the accumulation of organisms on surfaces immersed in water. It is of particular concern to the international shipping industry because it increases fuel costs and presents a biosecurity risk by providing a pathway for non-indigenous marine species to establish in new areas. There is growing interest within jurisdictions to strengthen biofouling risk-management regulations, but it is expensive to conduct in-water inspections and assess the collected data to determine the biofouling state of vessel hulls. Machine learning is well suited to tackle the latter challenge, and here we apply deep learning to automate the classification of images from in-water inspections to identify the presence and severity of fouling. We combined several datasets to obtain over 10,000 images collected from in-water surveys which were annotated by a group biofouling experts. We compared the annotations from three experts on a 120-sample subset of these images, and found that they showed 89% agreement (95% CI: 87-92%). Subsequent labelling of the whole dataset by one of these experts achieved similar levels of agreement with this group of experts, which we defined as performing at most 5% worse (p=0.009-0.054). Using these expert labels, we were able to train a deep learning model that also agreed similarly with the group of experts (p=0.001-0.014), demonstrating that automated analysis of biofouling in images is feasible and effective using this method.Comment: 12 page

Simulated Galactic Cosmic Radiation Exposure Impairs Mouse Vertebral Bone Adaptations to Exercise During Recovery From Partial Weightbearing

Partial weightbearing that simulates Lunar gravity (1/6th of Earth’s gravitational force) results in a loss of bone volume. High energy radiation like that found in galactic cosmic radiation exposure also negatively affects the skeleton. Because resistance training is the most effective exercise mode to counteract disuse-induced bone loss, this experiment combined low-dose, high-energy simulated galactic cosmic radiation (GCR) exposure, followed by a period of partial weightbearing (PWB), and then a period of resistance exercise or normal cage activity during recovery. Young adult female BALB/c mice were randomly assigned to age-matched cage controls (CC) or PWB (G/6) groups. From there, animals were further divided into 0.5 Gy 36Fe radiation exposure (RAD) or sham exposure (SHAM) groups. Radiation exposure was performed at NASA’s Space Radiation Laboratory at Brookhaven National Laboratory before shipping to Texas A&M. GCR was followed by a 21-day period of PWB, equivalent to being placed in a simulated lunar gravity environment. A 21-day recovery period began on Day 22, during which PWB animals were assigned to one of two groups: recovery with normal cage activity (G/6 + Rec) or resistance training during recovery (G/6 + RecEX). The latter group was trained three times every four days with a tower climbing training regimen, climbing a 1-meter wire mesh tower at an 85° angle. This training was repeated for a total of 15 climb sessions. As the exercise period progressed, weights were taped on to the mice tails. Ex vivo micro-computed tomography (μCT) scans were performed by Matthew Allen, PhD at the Indiana University School of Medicine to quantify cancellous bone microarchitecture in the 4th lumbar vertebral body. Means for cancellous bone volume (%BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) from Day 42 of the experiment were compared to Day 21 means by 2-way ANOVA to determine the changes occurring through the recovery period. RecEX had no significant affect on ∆BV/TV or ∆Tb.Th, but ∆BV/TV and ∆Tb.Th were significantly lower in RAD groups than in SHAM groups (p\u3c0.001). ∆Tb.N was significantly higher in exercised groups than non-exercised groups (p\u3c0.05), but no significant differences in ∆Tb.N were shown between RAD and SHAM groups. These data suggest that GCR exposure diminishes the ability of bone to respond to exercise during recovery form a period of reduced weightbearing

Impact of Non Steroidal Anti-Inflammatory Drug Administration Pre- or Post-Resistance Training on Bone

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been shown to suppress bone formation when administered before, but not if administered after, an acute bout of mechanical load. The effects of giving NSAIDs pre- and post-resistance training over multiple training sessions are not yet well defined. Therefore, the aim of this study was to elucidate the effects of NSAIDs when administered pre and post simulated resistance training (SRT) in a small animal model. We hypothesize that gains in bone mass and increased bone size will be diminished in adult rats given ibuprofen before each training session, but will be enhanced if ibuprofen is given after each exercise bout. Methods: Fifteen 5-month-old virgin female Sprague-Dawley rats completed 9 SRT sessions at 75% peak isometric strength for 4 sets of 5 repetitions; each contraction included 1 sec isometric + 1 sec eccentric contraction. Animals were blocked assigned by body weight to one of three groups: (1) ibuprofen (30mg/kg) before exercise, placebo after (I:P)(n=4), (2) placebo before exercise, ibuprofen after (P:I)(n=5) and (3) placebo before exercise, placebo after (P:P)(n=6). In vivo pQCT scans measured changes in total volumetric bone mineral density (vBMD), cancellous vBMD, and total area at the proximal tibia, and cortical vBMD, cortical bone mineral content (BMC) and total area at midshaft tibia from days -7 and 21. Body weights were measured at days 4, 14 and 21. Results: There were no significant changes in body weight over the course of the study (P:P -2.6%, I:P -2.3% & P:I -3.8%, day 21 vs day 4). Furthermore, there was no significant difference across time in midshaft cortical vBMD, but the P:I group did exhibit a significantly different response in cortical vBMD when normalized to body weight (+5.1%) (p\u3c .05) compared to I:P (-1.4%) and P:P (-0.3%). There were no differences among groups for change in cancellous vBMD, total vBMD and total area at the proximal region, as well as cortical BMC and total area at midshaft tibia. Conclusion: These data are preliminary but suggest that ibuprofen given after exercise may produce additional gains in cortical bone following resistance training; we have no evidence thus far that ibuprofen taken before exercise has any effect. Supported by Huffines Institute of Sports Medicine and Human Performance, Texas A&M University

Short-Term Reduction in Energy Availability Does Not Impair Exercise-Induced Gains in Bone Formation Rate

Reduced energy availability (EA, defined as total energy intake minus exercise energy expenditure) can induce significant bone loss in humans and in rodents, but this effect may vary with exercise status. Purpose: This study focused on the effects of graded reductions in EA achieved with and without exercise on mid-shaft tibia cortical bone. We hypothesized that markers of bone formation would be reduced with 4 weeks of decreased EA, but these reductions would be mitigated in exercising animals. Methods: After 8 weeks of acclimation to AIN-93M purified diet, 5 mo-old virgin female Sprague-Dawley rats (n=72) were randomized in to sedentary (SED) and exercise (EX) groups, each of which was divided into 3 energy status groups: -12% EA/g body mass (-12EA) and -25% EA/g body mass (-25EA) vs. ad lib-fed controls. EX rats were restricted on diet intake slightly less than SED to account for the energy cost (+10%/day) of treadmill running (80-90 min/d, 4 d/wk, ~60% VO2max); custom versions of AIN-93M were used to assure restriction of only kcal (other nutrients at 100%). Calcein injections 9 and 2 days prior to euthanasia labeled mineralizing surfaces for histomorphometric analyses 2 mm proximal to the tibio-fibular junction for mineralizing surface (%MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR) on periosteal and endocortical surfaces. Results: After 4 weeks, only -25EA SED lost body mass (-11%); virtually all of this was fat mass. Periosteal BFR was 2 to 4 fold higher in EX rats vs. SED animals within each energy status group. The impact of EX on endocortical BFR was even greater (~5-fold increase) for all groups except in the -25 EA cohorts (-25 EA EX BFR ~ equal to -25EA SED BFR). Increases in BFR with EX were achieved by increases in both %MS/BS and MAR on both cortical surfaces. Conclusions: These data suggest that short-term graded reductions in EA do not inhibit BFR in SED animals nor the robust stimulation of BFR by moderately vigorous exercise training. The one exception observed was a suppression of the EX induced gain in endocortical BFR with the more stringent level of reduced EA. Whether this lack of effect of EA on BFR gains with EX persists with more chronic reductions in EA has yet to be determined. Funded by the Department of Defense #WSIXWH-06-1-047

Impact of Anti-Resorptive Treatment on Recovery of Bone After Disuse

Bisphosphonates (BP), drugs that inhibit bone resorption, are used to minimize bone loss in long-duration spaceflight, extended bed rest, and acute spinal cord injury; however, the long term impact of BP use on recovery of bone after disuse is not well understood. This experiment tests the hypothesis that the BP zoledronic acid (ZOL) administered 7 days before hindlimb unloading (HU) will protect against loss of bone mass during 28 days of HU by suppressing bone resorption activity while also diminishing the ability of cancellous bone formation rate (BFR) to recover following HU. Male Sprague Dawley rats (6 mo) were assigned to aging control (AC), HU, and HU+ZOL groups and subjected to 28 days of HU, then to 56 days of weight-bearing recovery (REC). One group of rats was given 2 fluorescent labels 7 days apart to measure BFR in the final week of HU and the other group was given the same labels in the final week of REC. Histomorphometric analyses of the proximal tibia and distal femur showed lower osteoclast surface, a measure of bone resorption, 35 days after injection and 119 days after injection (-50% and -75%, respectively, compared to HU). This verified that ZOL successfully suppressed bone resorption. Dynamic histomorphometry revealed that cancellous BFR was lower in ZOL+HU versus AC both immediately after HU (-96.6%) and after the recovery period (-99.9%) (