Comparison of radiography and computed tomography for identification of third metacarpal structural change and associated assessment of condylar stress fracture risk in Thoroughbred racehorses.

BACKGROUND: Catastrophic injury has a low incidence but leads to the death of many Thoroughbred racehorses. OBJECTIVES: To determine sensitivity, specificity, and reliability for third metacarpal condylar stress fracture risk assessment from digital radiographs (DR) and standing computed tomography (sCT). STUDY DESIGN: Controlled ex vivo experiment. METHODS: A blinded set of metacarpophalangeal joint DR and sCT images were prepared from 31 Thoroughbreds. Four observers evaluated the condyles and parasagittal grooves (PSG) of the third metacarpal bone for the extent of dense bone and lucency/fissure and assigned a risk assessment grade for condylar stress fracture based on imaging features. Sensitivity and specificity for detection of subchondral structural changes in the condyles and PSG, and for risk assessment for condylar stress fracture were determined by comparison with a reference assessment based on sCT and joint surface examination. Agreement between observers and the reference assessment and reliability between observers were determined. Intra-observer repeatability was also assessed. RESULTS: Sensitivity for detection of structural change was lower than specificity for both imaging methods and all observers. For agreement with the reference assessment of structural change, correlation coefficients were generally below 0.5 for DR and 0.49-0.82 for sCT. For horses categorised as normal risk on reference assessment, observer assessment often agreed with the reference. Sensitivity for risk assessment was lower than specificity for all observers. For horses with a reference assessment of high risk of injury, observers generally underestimated risk. Diagnostic sensitivity of risk assessment was improved with sCT imaging, particularly for horses categorised as having elevated risk of injury from the reference assessment. Assessment repeatability and reliability was better with sCT than DR. MAIN LIMITATIONS: The ex vivo study design influenced DR image sets. CONCLUSIONS: Risk assessment through screening with diagnostic imaging is a promising approach to improve injury prevention in racing Thoroughbreds. Knowledge of sensitivity and specificity of fetlock lesion detection provides the critical guidance needed to improve racehorse screening programs. We found improved detection of MC3 subchondral structural change and risk assessment for condylar stress fracture with sCT ex vivo.

Galectin-3 as a Prognostic Biomarker of Left Ventricular Assist Device Implantation Outcomes.

We assessed the prognostic potential of Galectin-3 in a sample of 159 heart failure patients who received a left ventricular assist device (LVAD) implant from 2012 to 2020. Clinical outcomes included hemodynamic data, right heart failure (RHF), hemocompatibility-related adverse events (HRAEs), and mortality. Galectin-3 was compounded into Michigan-RVF and EUROMACS-RHF risk scores and compared to the noncompounded risk scores. Right heart failure was significantly correlated with Galectin (p = 0.004) on a continuous spectrum. Inotrope duration was significantly correlated to Galectin-3 (interquartile range [IQR]: 7.58-8.65, p < 0.001) along with INTERMACS score (IQR: 2.14-1.90, p < 0.001). Intensive care unit length of stay (median 8 days, p = 0.02), blood urea nitrogen (p < 0.001), creatinine (p < 0.001), and pulmonary artery pulsatility index (p = 0.05) were also significantly correlated with Galectin-3. In our c-statistic analysis, the predictive value for RHF improved when Galectin-3 was included for both the Michigan-RVF (0.80-0.86) and EUROMACS-RHF (0.77-0.82) risk scores. When elevated over a binary cutoff of 18.2 ng/ml, Galectin-3 significantly correlated with HRAEs (p = 0.014) and mortality (p = 0.031). Galectin-3 shows great promise as a predictive biomarker in patients implanted with durable LVADs. In addition to significant correlation with key clinical outcomes, Galectin-3 enhanced the Michigan-RVF and EUROMACS-RHF risk scores in predicting progression to RHF.

Croton gratissimus Burch Herbal Tea Exhibits Anti-Hyperglycemic and Anti-Lipidemic Properties via Inhibition of Glycation and Digestive Enzyme Activities.

Over the years, the world has continued to be plagued by type 2 diabetes (T2D). As a lifestyle disease, obese individuals are at higher risk of developing the disease. Medicinal plants have increasingly been utilized as remedial agents for managing metabolic syndrome. The aim of the present study was to investigate the in vitro anti-hyperglycemic and anti-lipidemic potential of Croton gratissimus herbal tea infusion. The inhibitory activities of C. gratissimus on carbohydrate (α-glucosidase and α-amylase) and lipid (pancreatic lipase) hydrolyzing enzymes were determined, and the mode of inhibition of the carbohydrate digestive enzymes was analyzed and calculated via Lineweaver-Burk plots and Michaelis Menten's equation. Its effect on Advanced Glycation End Product (AGE) formation, glucose adsorption, and yeast glucose utilization were also determined. High-performance liquid chromatography (HPLC) was used to quantify the possible phenolic compounds present in the herbal tea infusion, and the compounds were docked with the digestive enzymes. C. gratissimus significantly (p < 0.05) inhibited α-glucosidase (IC50 = 60.56 ± 2.78 µg/mL), α-amylase (IC50 = 35.67 ± 0.07 µg/mL), as well as pancreatic lipase (IC50 = 50.27 ± 1.51 µg/mL) in a dose-dependent (15-240 µg/mL) trend. The infusion also inhibited the non-enzymatic glycation process, adsorbed glucose effectively, and enhanced glucose uptake in yeast cell solutions at increasing concentrations. Molecular docking analysis showed strong binding affinity between HPLC-quantified compounds (quercetin, caffeic acid, gallic acid, and catechin) of C. gratissimus herbal tea and the studied digestive enzymes. Moreover, the herbal tea product did not present cytotoxicity on 3T3-L1 cell lines. Results from this study suggest that C. gratissimus herbal tea could improve glucose homeostasis and support its local usage as a potential anti-hyperglycemic and anti-obesogenic agent. Further in vivo and molecular studies are required to bolster the results from this study.

Afraid and tired: A longitudinal study of the relationship between cancer-related fatigue and fear of cancer recurrence in long-term cancer survivors.

OBJECTIVE: Cancer-related fatigue (CRF) and fear of cancer recurrence (FCR) are two common concerns experienced by cancer survivors. However, the relationship between these two concerns is poorly understood, and whether CRF and FCR influence each other over time is unclear. METHODS: Data were from a national, prospective, longitudinal study, the American Cancer Society's Study of Cancer Survivors-I (SCS-I). Surveys were completed by 1395 survivors of 10 different cancer types at three time-points, including assessment 1.3 years (T1), 2.2 years (T2) and 8.8 years (T3) following their cancer diagnosis. CRF was assessed using the fatigue-inertia subscale of the Profile of Mood States, and FCR by the FCR subscale of the Cancer Problems in Living Scale. Multiple group random intercepts cross-lagged panel models investigated prospective associations between CRF and FCR. RESULTS: For younger participants (at or below median age of 55 years, n = 697), CRF at T1 and T2 marginally and significantly predicted FCR at T2 and T3, respectively, but no lagged effects of FCR on subsequent CRF were observed. Cross-lagged effects were not observed for survivors over 55 years of age. CONCLUSION: Both CRF and FCR are debilitating side effects of cancer and its treatments. Given that CRF may be predictive of FCR, it possible that early detection and intervention for CRF could contribute to lowering FCR severity.

Nf1 deficiency modulates the stromal environment in the pretumorigenic rat mammary gland.

Background: Neurofibromin, coded by the NF1 tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1)-a tumor predisposition syndrome caused by a germline NF1 mutation-have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by which NF1 mutations lead to breast cancer tumorigenesis is not well understood. Therefore, the objective of this work was to identify stromal alterations before tumor formation that result in the increased risk and poorer outcome seen among NF1 patients with breast cancer. Approach: To accurately model the germline monoallelic NF1 mutations in NF1 patients, we utilized an Nf1-deficient rat model with accelerated mammary development before presenting with highly penetrant breast cancer. Results: We identified increased collagen content in Nf1-deficient rat mammary glands before tumor formation that correlated with age of tumor onset. Additionally, gene expression analysis revealed that Nf1-deficient mature adipocytes in the rat mammary gland have increased collagen expression and shifted to a fibroblast and preadipocyte expression profile. This alteration in lineage commitment was also observed with in vitro differentiation, however, flow cytometry analysis did not show a change in mammary adipose-derived mesenchymal stem cell abundance. Conclusion: Collectively, this study uncovered the previously undescribed role of Nf1 in mammary collagen deposition and regulating adipocyte differentiation. In addition to unraveling the mechanism of tumor formation, further investigation of adipocytes and collagen modifications in preneoplastic mammary glands will create a foundation for developing early detection strategies of breast cancer among NF1 patients.

Novel Virtual Reality App for Training Patients on MRI-guided Radiation Therapy.

Purpose: Patients receiving respiratory gated magnetic resonance imaging-guided radiation therapy (MRIgRT) for abdominal targets must hold their breath for ≥25 seconds at a time. Virtual reality (VR) has shown promise for improving patient education and experience for diagnostic MRI scan acquisition. We aimed to develop and pilot-test the first VR app to educate, train, and reduce anxiety and discomfort in patients preparing to receive MRIgRT. Methods and Materials: A multidisciplinary team iteratively developed a new VR app with patient input. The app begins with minigames to help orient patients to using the VR device and to train patients on breath-holding. Next, app users are introduced to the MRI linear accelerator vault and practice breath-holding during MRIgRT. In this quality improvement project, clinic personnel and MRIgRT-eligible patients with pancreatic cancer tested the VR app for feasibility, acceptability, and potential efficacy for training patients on using breath-holding during MRIgRT. Results: The new VR app experience was tested by 19 patients and 67 clinic personnel. The experience was completed on average in 18.6 minutes (SD = 5.4) by patients and in 14.9 (SD = 3.5) minutes by clinic personnel. Patients reported the app was "extremely helpful" (58%) or "very helpful" (32%) for learning breath-holding used in MRIgRT and "extremely helpful" (28%) or "very helpful (50%) for reducing anxiety. Patients and clinic personnel also provided qualitative feedback on improving future versions of the VR app. Conclusion: The VR app was feasible and acceptable for training patients on breath-holding for MRIgRT. Patients eligible for MRIgRT for pancreatic cancer and clinic personnel reported on future improvements to the app to enhance its usability and efficacy.

Subchondral bone fatigue injury in the parasagittal condylar grooves of the third metacarpal bone in thoroughbred racehorses elevates site-specific strain concentration.

Condylar stress fracture of the distal end of the third metacarpal/metatarsal (MC3/MT3) bones is a major cause of Thoroughbred racehorse injury and euthanasia worldwide. Functional adaptation to exercise and fatigue damage lead to structural changes in the subchondral bone that include increased modeling (resulting in sclerotic bone tissue) and targeted remodeling repair (resulting in focal resorption spaces in the parasagittal groove). Whether these focal structural changes, as detectable by standing computed tomography (sCT), lead to elevated strain at the common site of condylar stress fracture has not been demonstrated. Therefore, the goal of the present study was to compare full-field three-dimensional (3D) strain on the distopalmar aspect of MC3 bone specimens with and without focal subchondral bone injury (SBI). Thirteen forelimb specimens were collected from racing Thoroughbreds for mechanical testing ex vivo and underwent sCT. Subsequently, full-field displacement and strain at the joint surface were determined using stereo digital image correlation. Strain concentration was observed in the parasagittal groove (PSG) of the loaded condyles, and those with SBI in the PSG showed higher strain rates in this region than control bones. PSG strain rate in condyles with PSG SBI was more sensitive to CT density distribution in comparison with condyles with no sCT-detectable injury. Findings from this study help to interpret structural changes in the subchondral bone due to fatigue damage and to assess risk of incipient stress fracture in a patient-specific manner.

Long-term multimorbidity trajectories in older adults: The role of cancer, demographics, and health behaviors.

BACKGROUND: Multimorbidity is associated with premature mortality and excess health care costs. The burden of multimorbidity is highest among patients with cancer, yet trends and determinants of multimorbidity over time are poorly understood. METHODS: Via Medicare claims linked to Cancer Prevention Study II data, group-based trajectory modeling was used to compare National Cancer Institute comorbidity index score trends for cancer survivors and older adults without a cancer history. Among cancer survivors, multinomial logistic regression analyses evaluated associations between demographics, health behaviors, and comorbidity trajectories. RESULTS: In 82,754 participants (mean age, 71.6 years [SD, 5.1 years]; 56.9% female), cancer survivors (n = 11,265) were more likely than older adults without a cancer history to experience the riskiest comorbidity trajectories: (1) steady, high comorbidity scores (remain high; odds ratio [OR], 1.36; 95% CI, 1.29-1.45), and (2) high scores that increased over time (start high and increase; OR, 1.51; 95% CI, 1.38-1.65). Cancer survivors who were physically active postdiagnosis were less likely to fall into these two trajectories (OR, 0.73; 95% CI, 0.64-0.84, remain high; OR, 0.42; 95% CI, 0.33-0.53, start high and increase) compared to inactive survivors. Cancer survivors with obesity were more likely to have a trajectory that started high and increased (OR, 2.83; 95% CI, 2.32-3.45 vs. normal weight), although being physically active offset some obesity-related risk. Cancer survivors who smoked postdiagnosis were also six times more likely to have trajectories that started high and increased (OR, 6.86; 95% CI, 4.41-10.66 vs. never smokers). CONCLUSIONS: Older cancer survivors are more likely to have multiple comorbidities accumulated at a faster pace than older adults without a history of cancer. Weight management, physical activity, and smoking avoidance postdiagnosis may attenuate that trend.

Failure in articular cartilage: Finite element predictions of stress, strain, and pressure under micro-indentation induced fracture.

Articular cartilage is found at the distal end of long bones and is responsible for assisting in joint articulation. While articular cartilage has remarkable resistance to failure, once initially damaged, degeneration is nearly irreversible. Thus, understanding damage initiation is important. There are a few proposed mechanisms for articular cartilage failure initiation: (A) a single collagen fibril stress-based regime; (B) a rate-dependent regime captured by brittle failure at slow displacement rates (SDR) and ductile failure at fast displacement rates (FDR); and (C) a rate-dependent regime where failure is governed by pressurization fragmentation at SDR and governed by strain at FDR. The objective of this study was to use finite element (FE) models to provide evidence to support or refute these proposed failure mechanisms. Models were developed of microfracture experiments that investigated osmolarity (hypo-osmolar, normal osmolarity, and hyper-osmolar) and displacement rate (FDR and SDR) effects. Cartilage was modeled with a neo-Hookean ground matrix, strain-dependent permeability, nonlinear fibril reinforcement with viscoelastic fibril terms, and Donnan equilibrium swelling. Total stress, solid matrix stress, Lagrange strain, and fluid pressure were determined under the indenter tip at the moment of microfracture. Results indicated significant rate dependence across multiple outputs, which does not support (A) a single failure regime. Larger solid and fluid pressures at FDR than SDR did not support (C) a rate-dependent regime split by pressurization at SDR and strain at FDR. Consistent solid shear stresses at SDR and consistent third principal solid stresses at FDR support (B) the ductile-brittle failure regime. These findings help to shed light on the underlying mechanisms of articular cartilage failure, which have implications for the development of osteoarthritis.

"I Just Want to be Acknowledged": Suicidal Ideation Experiences among Sexual Minority Students at a Religiously Affiliated University.

Research finds that sexual minority university students experience considerable psychological and emotional distress. Furthermore, a recent study at Brigham Young University (BYU)-a university affiliated with The Church of Jesus Christ of Latter-day Saints-found that suicidality prevalence and severity were twice as high among sexual minority students compared to their heterosexual peers. To better understand this finding, we interviewed ten sexual minority students at BYU who reported clinically significant current or previous suicidality. A coding team and auditors then analyzed and categorized the transcripts of these interviews using the Consensual Qualitative Research methodology. Five domains emerged related to suicidality among sexual minority students: deterrents from suicidal ideation and intent; contributors to suicidal ideation and intent; religious and spiritual experiences; experiences with BYU; and suggested improvements. We found patterns consistent with previous literature, including relational and belonging factors contributing to suicidality; we also found that certain doctrinal interpretations were related to increased suicidality. The primary improvement requested by participants was feeling better understood and accepted (rather than ignored or marginalized). We discuss study limitations (including small sample size and low generalizability,), future directions for research, and implications for religious university campuses.

Effect of mineral diets on the development of cartilage material properties.

Vitamin D and minerals, including zinc (Zn) and manganese (Mn), are vital in the development of bones, but their roles in the development of articular cartilage material behavior are not well understood. In this study, articular cartilage material properties from a hypovitaminosis D porcine model were evaluated. Pigs were produced by sows fed vitamin D deficient diets during gestation and lactation, and the offspring were subsequently fed vitamin D deficient diets for 3 weeks during the nursery period. Pigs were then assigned to dietary treatment groups with inorganic minerals only or inorganic plus organic (chelated) minerals. Humeral heads were harvested from pigs at 24 weeks of age. Linear elastic modulus and dissipated energy were measured under compression to 15% engineering strain at 1 Hz. Anatomical location within the humeral head affected elastic modulus. Diet significantly affected linear modulus and dissipated energy. The largest modulus and highest energy dissipation was in the inorganic zinc and manganese group; the lowest modulus and the least energy dissipation was in the organic (chelated) zinc and manganese group. Pairwise results between the control group and all vitamin D deficient groups were not statistically significant. Overall, these results suggest that mineral availability during rapid growth subsequent to a vitamin-D deficiency during gestation and lactation had minimal effects on articular cartilage material properties in young growing pigs. Though not statistically significant, some of the numerical differences between mineral sources suggest the potential importance of mineral availability during cartilage formation and warrant further study.

Correlation of mineral density and elastic modulus of dog dentin using µ-CT and nanoindentation.

This study sought to 1) investigate the spatial distribution of mineral density of dog dentin using µ-CT and 2) characterize the relationship between the elastic modulus and mineral density of dog dentin using nanoindentation and µ-CT. Maxillary canine teeth of 10 mature dogs were scanned with a µ-CT then sectioned in the transverse and vertical planes and tested using nanoindentation. Spatial distribution of mineral density and elastic modulus was quantified. Results demonstrated significant spatial variation in mineral density and elastic modulus. Mineral density and elastic modulus generally increased from the dentin-pulp interface to the dentino-enamel junction and from the crown base to the crown tip. Significant site dependent correlations between mineral density and elastic modulus were determined (0.021 > R2 > 0.408). The results of this study suggest that while mineral density is a mediator of elastic modulus, other mediators such as collagen content may contribute to the mechanical behavior of dog dentin.

Assessing the impact of religious resources and struggle on well-being: a report from the American Cancer Society's Study of Cancer Survivors-I.

PURPOSE: The current study examined the relationships between religious resources (i.e., certainty of belief in God and attendance at religious services), religious struggle (e.g., belief that cancer is evidence of God's punishment or abandonment), and physical and mental health-related quality of life (HRQoL), including fear of cancer recurrence (FCR), in a large, geographically and clinically diverse sample of long-term survivors of cancer. METHODS: Participants were 2021 9-year survivors of cancer from the American Cancer Society's Study of Cancer Survivors - I. Religious resources included belief in God and attendance at religious services. Items from the Brief RCOPE and the PROMIS Psychosocial Impact of Illness were combined to assess religious struggle. Survivors also completed the Fear of Cancer Recurrence Inventory, SF-12, and Meaning and Peace subscales of the FACIT-Sp. Regression models were used to predict HRQoL and FCR from religious resources and struggle. RESULTS: In multivariable models, certain belief in God predicted greater mental HRQoL (B = 1.99, p < .01), and attendance at religious services was associated with greater FCR (B = .80, p < .05) as well as better mental (B = .34, p < .01) and physical (B = .29, p < .05) HRQoL. In addition, religious struggle predicted greater FCR (B = 1.32, p < .001) and poorer mental (B = - .59, p < .001) and physical (B = - .29, p < .001) HRQoL. Many of these relationships were mediated through Meaning. CONCLUSIONS: With the exception of FCR, religious resources predicted better HRQoL outcomes in these long-term survivors of cancer. Conversely, religious struggle consistently predicted poorer HRQoL, including greater FCR. IMPLICATIONS FOR CANCER SURVIVORS: Given the documented importance of its role in coping with the cancer experience, religion/spirituality should be a consideration in every survivorship care plan. Multidisciplinary assessment and support of religious resources and identification of and referral for religious struggle are needed to ensure the well-being of most long-term survivors of cancer.

Fracture Risk Among Older Cancer Survivors Compared With Older Adults Without a History of Cancer.

Importance: The number of cancer survivors living in the US is projected to be 26.1 million by 2040. Cancer survivors may be at increased risk of bone fractures, but research is limited in several important ways. Objective: To investigate the associations of cancer diagnoses, including time since diagnosis and stage at diagnosis, with risks of pelvic, radial, and vertebral fractures (separately and combined) among older cancer survivors and compared with fracture risk among older adults without a history of cancer. Secondarily, to examine differences in risk of fracture stratified by modifiable behaviors, treatment, and cancer type. Design, Setting, and Participants: This longitudinal cohort study used data from 92 431 older adults in the US Cancer Prevention Study II Nutrition Cohort linked with 1999 to 2017 Medicare claims. Data were analyzed from July 15, 2021, to May 3, 2022. Exposures: Cancer history, time since cancer diagnosis, and stage at cancer diagnosis. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for the risk of pelvic, radial, vertebral, and total frailty-related fractures were estimated using multivariate Cox proportional hazards regression. Stratification was used for secondary aims. Results: Among 92 431 participants (mean [SD] age, was 69.4 [6.0] years, 51 820 [56%] women, and 90 458 [97.9%] White], 12 943 participants experienced a frailty-related bone fracture. Compared with participants without a history of cancer, cancer survivors who were diagnosed 1 to less than 5 years earlier with advanced stage cancer had higher risk of fracture (HR, 2.12; 95% CI, 1.75-2.58). The higher fracture risk in cancer survivors with recent advanced stage diagnosis (vs no cancer) was driven largely by vertebral (HR, 2.46; 95% CI, 1.93-3.13) and pelvic (HR, 2.46; 95% CI, 1.84-3.29) fracture sites. Compared with cancer survivors who did not receive chemotherapy, survivors who received chemotherapy were more likely to have a fracture; this association was stronger within 5 years of diagnosis (HR, 1.31; 95% CI, 1.09-1.57) than 5 or more years after diagnosis (HR, 1.22; 95% CI, 0.99-1.51). Although the HR for risk of fracture was lower among physically active cancer survivors 5 or more years after diagnosis (HR, 0.76; 95% CI, 0.54-1.07), this result was not statistically significant, whereas current smoking was significantly associated with higher risk of fracture (HR, 2.27; 95% CI, 1.55-3.33). Conclusions and Relevance: Findings from this cohort study suggest that older adults with a history of cancer may benefit from clinical guidance on prevention of frailty-related fractures. If study findings are replicated, fracture prevention programs for survivors might include referrals for physical activity with cancer exercise professionals and smoking cessation programs.

Morphological quantification of the maxillary canine tooth in the domestic dog (Canis lupus familiaris).

Canine tooth shape is known to vary with diet and killing behavior in wild animals and the relationship between form and function is driven in part by selective pressure. However, comparative investigation of the domestic dog (Canis lupus familiaris) is of interest. How do they compare to their wild counterparts? This study sought to quantify and characterize the morphology of the canine tooth in the domestic dog, and to provide a preliminary investigation into the variance in canine tooth morphology across individual dogs of varying breeds. Three-dimensional (3D) models generated from micro-computed tomography (µ-CT) studies of 10 mature maxillary canine teeth from the domesticated dog (Canis lupus familiaris) were used to quantify key morphological features and evaluate variance among dogs. Results show that, utilizing modern imaging and model building software, the morphology of the canine tooth can be comprehensively characterized and quantified. Morphological variables such as second moment of area and section modulus (geometrical parameters related to resistance to bending), as well as aspect ratio, ridge sharpness, cusp sharpness and enamel thickness are optimized in biomechanically critical areas of the tooth crown to balance form and function. Tooth diameter, second moment of area, section modulus, cross sectional area, tooth volume and length as well as enamel thickness are highly correlated with body weight. In addition, we found preliminary evidence of morphological variance across individual dogs. Quantification of these features provide insight into the balance of form and function of the canine tooth in wild and domesticated canids. In addition, results suggest that variance between dogs exist in some morphological features and most morphological features are highly correlated with body weight.

Effect of osmolarity and displacement rate on cartilage microfracture clusters failure into two regimes.

Articular cartilage is a poroviscoelastic (PVE) material with remarkable resistance to fracture and fatigue failure. Cartilage failure mechanisms and material properties that govern failure are incompletely understood. Because cartilage is partially comprised of negatively charged glycosaminoglycans, altering solvent osmolarity can influence PVE relaxations. Therefore, this study aims to use osmolarity as a tool to provide additional data to interpret the role of PVE relaxations and identify cartilage failure regimes. Cartilage fracture was induced using a 100 µm radius spheroconical indenter at controlled displacement rates under three different osmolarity solvents. Secondarily, contact pressure (CP) and strain energy density (SED) were estimated to cluster data into two failure regimes with an expectation maximization algorithm. Critical displacement, critical load, critical time, and critical work to fracture increased with increasing osmolarity at a slow displacement rate whereas no significant effect was observed at a fast displacement rate. Clustering provided two distinct failure regimes, with regime (I) at lower normalized thickness (contact radius divided by sample thickness), and regime (II) at higher normalized thickness. Varied CP and SED in regime (I) suggest that failure in the regime is strain-governed. Constant CP and SED in regime (II) suggests that failure in the regime is dominantly governed by stress. These regimes can be interpreted as ductile versus brittle, or using a pressurized fragmentation interpretation. These findings demonstrated fundamental failure properties and postulate failure regimes for articular cartilage.

Vitamin D deficiency and anatomical region alters porcine growth plate properties.

Ossification of growth plate cartilage mediates longitudinal extension of long bones. Biomechanical and biochemical disruptions of growth plate function may lead to abnormal bone growth. In humans and animals, severe dietary vitamin D deficiency can lead to rickets which features growth plate widening, resulting in abnormalities in growth. However, effects of marginal vitamin D deficiencies on growth plates are not well understood. The purpose of this study was to examine the effects of a vitamin D deficient diet in the 26-day nursery phase on mechanical properties (ultimate normal stress, ultimate shear stress, ultimate strain, and tangent modulus) of porcine growth plate. Standard uniaxial tensile tests were applied on bone-growth plate-bone sections and the total stress was decomposed into normal stress and shear stress. Ultimate shear stress and ultimate strain traits were lower in the vitamin D deficient group than in the control. Regional differences were observed in all four variables. Ultimate normal stress was higher in the anterior region, which was consistent with a previous study. Sex differences were detected in ultimate normal stress, which was higher in females than in males. Interestingly, the classical finding of growth plate widening seen in severe vitamin D deficiency was not observed in the pigs with marginal vitamin D deficiency utilized in this study.

Structure-function relationships in dog dentin.

Investigations into teeth mechanical properties provide insight into physiological functions and pathological changes. This study sought to 1) quantify the spatial distribution of elastic modulus, hardness and the microstructural features of dog dentin and to 2) investigate quantitative relationships between the mechanical properties and the complex microstructure of dog dentin. Maxillary canine teeth of 10 mature dogs were sectioned in the transverse and vertical planes, then tested using nanoindentation and scanning electron microscopy (SEM). Microstructural features (dentin area fraction and dentinal tubule density) and mechanical properties (elastic modulus and hardness) were quantified. Results demonstrated significant anisotropy and spatial variation in elastic modulus, hardness, dentin area fraction and tubule density. These spatial variations adhered to a consistent distribution pattern; hardness, elastic modulus and dentin area fraction generally decreased from superficial to deep dentin and from crown tip to base; tubule density generally increased from superficial to deep dentin. Poor to moderate correlations between microstructural features and mechanical properties (R2 = 0.032-0.466) were determined. The results of this study suggest that the other constituents may contribute to the mechanical behavior of mammalian dentin. Our results also present several remaining opportunities for further investigation into the roles of organic components (e.g., collagen) and mineral content on dentin mechanical behavior.

Age-related health deficits and five-year mortality among older, long-term cancer survivors.

INTRODUCTION: Geriatric assessment evaluates multiple domains of health that, together, are superior to using chronologic age for predicting outcomes, such as hospitalization and mortality among patients with cancer. Most studies have not included comparison groups of individuals without cancer and assessed domains around the time of initial cancer diagnosis. Further, the potential for brief, self-reported measures to capture deficits that similarly predict mortality has not been well examined. This study compared age-related health deficit prevalence between older, long-term cancer survivors and individuals without a cancer history, and estimated associations between deficits and mortality risk among survivors. MATERIALS AND METHODS: Analyses included participants in the Cancer Prevention Study (CPS)-II Nutrition Cohort who were cancer-free at enrollment in 1992/1993 and completed the Patient Reported Outcome Measurement Information System® (PROMIS®) global health questionnaire in 2011. Age-related deficits in five domains (comorbidities, functional status, mental health, malnutrition/weight loss, and social support) were self-reported. Cancer information was self-reported and confirmed via medical records or state cancer registries. Vital status through 2016 and cause of death was ascertained by linkage with the National Death Index. RESULTS: Analyses included 9979 participants (median age = 80) diagnosed with invasive cancer 5-20 years prior to completing the 2011 survey and 63,578 participants without a cancer history (median age = 79). Overall deficits in the five domains were similar among long-term cancer survivors and controls. However, survivors of specific cancer types - non-Hodgkin lymphoma (NHL), lung, and kidney cancer - were more likely to report deficits in mental health and functional status than the control group. Among all survivors, each domain was independently associated with all-cause mortality, particularly functional status (hazard ratio [HR] = 2.02; 95% confidence interval [CI]: 1.80-2.27) and mental health (HR = 1.84; 95% CI: 1.65-2.04). Mortality risk increased with the number of deficits. DISCUSSION: These results suggest that, several years after treatment, NHL, lung, and kidney cancer survivors are still more likely to experience age-related deficits compared to other similarly-aged individuals. Furthermore, results show that shorter, self-reported physical and mental health assessments, such as the PROMIS® global health questions, are predictive of mortality among older, long-term cancer survivors and, therefore, may be useful in clinical and research settings.