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Osteochondritis dissecans (OCD) is a chronic disease of the articular cartilage characterized by focal lesions of subchondral bone and overlaying cartilage. Through the growing number of reports describing the high prevalence of OCD in some families, the subcategory termed familial OCD (FOCD) was established. With the development of genetic approaches such as genome-wide association studies and sequencing, aggrecan (ACAN) has been identified as one of the genes of interest associated with FOCD. Aggrecan is a crucial protein for the preservation and function of cartilage. However, due to FOCD being characterized relatively recently, there is a paucity of literature on the subject. The purpose of this review is to explore the relationship between ACAN mutations and familial OCD as well as to explore current treatment options and avenues for future research. In vitro and animal studies have shown the importance of ACAN in the preservation of cartilage. However, the only human ACAN mutation related to OCD ever identified is a V2303M mutation in the G3 domain. Multiple treatments have been superficially explored, and some options such as growth hormone (GH) and gonadotrophin-releasing hormone agonists (GnRHa) show potential. Thus, further research on FOCD in needed to identify other ACAN mutations and determine optimal treatment modalities for this patient population.

Background Despite it being known that subchondral bone affects the viscoelasticity of cartilage, there has been little research into the mechanical properties of osteochondral tissue as a whole system. This study aims to unearth new knowledge concerning the dynamic behaviour of human subchondral bone and how energy is transferred through the cartilage-bone interface. Methods Dynamic mechanical analysis was used to determine the frequency-dependent (1–90 Hz) viscoelastic properties of the osteochondral unit (cartilage-bone system) as well as isolated cartilage and bone specimens extracted from human femoral heads obtained from patients undergoing total hip replacement surgery, with a mean age of 78 years (N = 5, n = 22). Bone mineral density (BMD) was also determined for samples using micro-computed tomography as a marker of tissue health. Results Cartilage storage and loss moduli along with bone storage modulus were found to increase logarithmically (p p − 1, while the loss stiffness was determined to be frequency-independent at 78.84 ± 2.48 N.mm− 1. Notably, a statistically significant (p p = 0.09). Conclusions The viscoelastic properties of the cartilage-bone core were significantly different to the tissues in isolation (p

Study Design An observational descriptive study based on a single cohort of patients. Objective To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in adolescent idiopathic scoliosis (AIS) patients. Summary of Background Data Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathology of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex compared with outside the curve in AIS patients. Methods Facet spinal tissue was collected perioperatively from three sites, the concave and convex side at the curve apex and from outside the curve (noncurve) from three AIS female patients aged 13–16 years. Spinal tissue was analyzed by micro–computed tomography to determine bone mineral density (BMD) and trabecular structure. Primary osteoblasts were cultured from concave, convex, and noncurve facet bone chips. The phenotype of osteoblasts was determined by assessment of cellular proliferation, cellular metabolism (alkaline phosphatase and Seahorse Analyzer), bone nodule mineralization (Alizarin red assay), and the mRNA expression of Wnt signaling genes (quantitative reverse transcriptase polymerase chain reaction). Results Convex facet tissue exhibited greater BMD and trabecular thickness, compared with concave facet tissue. Osteoblasts at the convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralized bone nodules, compared with concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts, compared with noncurve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts, compared with either concave or noncurve. Conclusions Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in AIS patients. Level of Evidence Level IV, Prognostic.

Background: Cannabis use is prevalent among adolescents, and many report using in attempts to alleviate negative mood and anxiety. Abstinence from substances such as alcohol and tobacco has been reported to improve symptoms of anxiety and depression. Few studies have examined the effect of cannabis abstinence on symptoms of anxiety and depression.Objective: To test the effect of 4 weeks of continuous cannabis abstinence on depressive and anxious symptoms.Methods: Healthy, non-treatment seeking adolescents who used cannabis at least weekly (n = 179) were randomized to either 4 weeks of cannabis abstinence achieved through a contingency management paradigm (CB-Abst) or cannabis use monitoring without an abstinence requirement (CB-Mon). Abstinence was assessed by self-report verified with quantitative assay of urine for cannabinoids. Anxiety and depressive symptoms were assessed weekly with the Mood and Anxiety Symptom Questionnaire (MASQ).Results: Symptoms of depression and anxiety decreased throughout the study for all participants (MASQ-AA: stnd beta = −0.08, p = 0.01, MASQ-GDA: stnd beta = −0.11, p = 0.003, MASQ-GDD: stnd beta = −0.08, p = 0.02) and did not differ significantly between randomization groups (p's > 0.46). Exploratory analyses revealed a trend that abstinence may be associated with greater improvement in symptoms of anxiety and depression among those using cannabis to cope with negative affect and those with potentially hazardous levels of cannabis use.Conclusions: Among adolescents who use cannabis at least weekly, 4 weeks of cannabis abstinence was not associated with a significant change in anxiety or depressive symptoms compared to continued use. For recreational cannabis users who may be concerned about reducing their use for fear of increased symptoms of anxiety and depression, findings suggest that significant symptom worsening may not occur within the first 4 weeks of abstinence. Further studies are needed in clinical populations where anxiety and depression symptoms are measured more frequently and for a longer period of abstinence. Future studies are also needed to determine whether there are subgroups of adolescents who are uniquely impacted by sustained cannabis abstinence.

The current gold standard technique for treatment of anterior cruciate ligament (ACL) injury is reconstruction with autograft. These treatments have a relatively high failure and re-tear rate. To overcome this, tissue engineering and additive manufacturing are being used to explore the potential of 3D scaffolds as autograft substitutes. However, mechanically optimal polymers for this have yet to be identified. Here, we use 3D printing technology and various materials with the aim of fabricating constructs better matching the mechanical properties of the native ACL. A fused deposition modeling (FDM) 3D printer was used to microfabricate dog bone-shaped specimens from six different polymers&mdash, PLA, PETG, Lay FOMM 60, NinjaFlex, NinjaFlex-SemiFlex, and FlexiFil&mdash, at three different raster angles. The tensile mechanical properties of these polymers were determined from stress&ndash, strain curves. Our results indicate that no single material came close enough to successfully match reported mechanical properties of the native ACL. However, PLA and PETG had similar ultimate tensile strengths. Lay FOMM 60 displayed a percentage strain at failure similar to reported values for native ACL. Furthermore, raster angle had a significant impact on some mechanical properties for all of the materials except for FlexiFil. We therefore conclude that while none of these materials alone is optimal for mimicking ACL mechanical properties, there may be potential for creating a 3D-printed composite constructs to match ACL mechanical properties. Further investigations involving co-printing of stiff and elastomeric materials must be explored.

Improving cardiovascular fitness may buffer against age-related cognitive decline and mitigate dementia risk by staving off brain atrophy. However, it is unclear if such effects reflect factors operating in childhood (neuroselection) or adulthood (neuroprotection). Using data from 807 members of the Dunedin Study, a population-representative birth cohort, we investigated associations between cardiovascular fitness and structural brain integrity at age 45, and the extent to which associations reflected possible neuroselection or neuroprotection by controlling for childhood IQ. Higher fitness, as indexed by VO2Max, was not associated with average cortical thickness, total surface area, or subcortical gray matter volume including the hippocampus. However, higher fitness was associated with thicker cortex in prefrontal and temporal regions as well as greater cerebellar gray matter volume. Higher fitness was also associated with decreased hippocampal fissure volume. These associations were unaffected by the inclusion of childhood IQ in analyses. In contrast, a higher rate of decline in cardiovascular fitness from 26 to 45 years was not robustly associated with structural brain integrity. Our findings are consistent with a neuroprotective account of adult cardiovascular fitness but suggest that effects are not uniformly observed across the brain and reflect contemporaneous fitness more so than decline over time.

Introduction Electronic cigarette (e-cigarette) use prevalence is increasing among U.S. adolescents and adults but recent longitudinal data for college/university students are scarce. Furthermore, the extent that e-cigarette use is associated with the onset of cigarette smoking and the factors that lead to the uptake of e-cigarettes in college students has not been explored. Methods 3757 participants from a Mid-Atlantic university (women: 66%; White: 45%; Black: 21%; Asian: 19%; Hispanic/Latino: 6%) were surveyed in 2014 and again in 2015. Results Among participants reporting never smoking at time 1, those who had ever tried e-cigarettes or were currently using e-cigarettes (at least one use in past 30 days) were more likely to have ever tried cigarettes by time 2 relative to individuals who had not used e-cigarettes. Ever use of e-cigarettes (but not current use) also increased participants' likelihood of being current cigarette smokers at time 2. Among initial never users of e-cigarettes or cigarettes, males and ever marijuana users had an increased probability of trying e-cigarettes by time 2. Furthermore, less perseverance (an index of impulsivity) and ever use of other tobacco products increased initial never users' chances of trying both cigarettes and e-cigarettes by time 2. Conclusions Given that never-smoking participants who had tried e-cigarettes were more likely to initiate cigarette use later, limiting young adults' access to these products may be beneficial. As the long-term health implications of e-cigarette use become clearer, predictors of e-cigarette use could help identify future populations likely to use and abuse these products.

Additive manufacturing (AM) has emerged over the past four decades as a cost-effective, on-demand modality for fabrication of geometrically complex objects. The ability to design and print virtually any object shape using a diverse array of materials, such as metals, polymers, ceramics and bioinks, has allowed for the adoption of this technology for biomedical applications in both research and clinical settings. Current advancements in tissue engineering and regeneration, therapeutic delivery, medical device fabrication and operative management planning ensure that AM will continue to play an increasingly important role in the future of healthcare. In this review, we outline current biomedical applications of common AM techniques and materials.