A mathematical model of signalling molecule-mediated processes during regeneration of osteochondral defects after chondrocyte implantation.

Treating bone-cartilage defects is a fundamental clinical problem. The ability of damaged cartilage to self-repair is limited due to its avascularity. Left untreated, these defects can lead to osteoarthritis. Details of osteochondral defect repair are elusive, but animal models indicate healing occurs via an endochondral ossification-like process, similar to that in the growth plate. In the growth plate, the signalling molecules parathyroid hormone-related protein (PTHrP) and Indian Hedgehog (Ihh) form a feedback loop regulating chondrocyte hypertrophy, with Ihh inducing and PTHrP suppressing hypertrophy. To better understand this repair process and to explore the regulatory role of signalling molecules on the regeneration process, we formulate a reaction-diffusion mathematical model of osteochondral defect regeneration after chondrocyte implantation. The drivers of healing are assumed to be chondrocytes and osteoblasts, and their interaction via signalling molecules. We model cell proliferation, migration and chondrocyte hypertrophy, and matrix production and conversion, spatially and temporally. We further model nutrient and signalling molecule diffusion and their interaction with the cells. We consider the PTHrP-Ihh feedback loop as the backbone mechanisms but the model is flexible to incorporate extra signalling mechanisms if needed. Our mathematical model is able to represent repair of osteochondral defects, starting with cartilage formation throughout the defect. This is followed by chondrocyte hypertrophy, matrix calcification and bone formation deep inside the defect, while cartilage at the surface is maintained and eventually separated from the deeper bone by a thin layer of calcified cartilage. The complete process requires around 48 months. A key highlight of the model demonstrates that the PTHrP-Ihh loop alone is insufficient and an extra mechanism is required to initiate chondrocyte hypertrophy, represented by a critical cartilage density. A parameter sensitivity study reveals that the timing of the repair process crucially depends on parameters, such as the critical cartilage density, and those describing the actions of PTHrP to suppress hypertrophy, such as its diffusion coefficient, threshold concentration and degradation rate.

Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria.

Successful diagnosis, screening, and elimination of malaria critically depend on rapid and sensitive detection of this dangerous infection, preferably transdermally and without sophisticated reagents or blood drawing. Such diagnostic methods are not currently available. Here we show that the high optical absorbance and nanosize of endogenous heme nanoparticles called "hemozoin," a unique component of all blood-stage malaria parasites, generates a transient vapor nanobubble around hemozoin in response to a short and safe near-infrared picosecond laser pulse. The acoustic signals of these malaria-specific nanobubbles provided transdermal noninvasive and rapid detection of a malaria infection as low as 0.00034% in animals without using any reagents or drawing blood. These on-demand transient events have no analogs among current malaria markers and probes, can detect and screen malaria in seconds, and can be realized as a compact, easy-to-use, inexpensive, and safe field technology.

Friendship chemistry: An examination of underlying factors☆.

Interpersonal chemistry refers to a connection between two individuals that exists upon first meeting. The goal of the current study is to identify beliefs about the underlying components of friendship chemistry. Individuals respond to an online Friendship Chemistry Questionnaire containing items that are derived from interdependence theory and the friendship formation literature. Participants are randomly divided into two subsamples. A principal axis factor analysis with promax rotation is performed on subsample 1 and produces 5 factors: Reciprocal candor, mutual interest, personableness, similarity, and physical attraction. A confirmatory factor analysis is conducted using subsample 2 and provides support for the 5-factor model. Participants with agreeable, open, and conscientious personalities more commonly report experiencing friendship chemistry, as do those who are female, young, and European/white. Responses from participants who have never experienced chemistry are qualitatively analyzed. Limitations and directions for future research are discussed.

Undetected eating disorders among adolescent psychiatric inpatients.

AIM: The aim of this study was to identify the prevalence of undetected eating disorders (EDs) among adolescent psychiatric inpatients and to investigate the association between clinical, psychiatric, and sociocultural factors and EDs. METHODS: Between January and December 2018, patients aged 12-18 years, hospitalized for inpatient-level treatment were given the self-assessment questionnaires of the Eating Attitudes Test-26 (EAT-26), the Contour Drawing Figure Rating Scale (CDFRS), the Child Behaviour Check List, and Sociocultural Attitudes Toward Appearance Questionnaire-4 after their routine unstructured clinical diagnostic assessment on admission by a psychiatrist. Patients were reassessed after reviewing the psychometric assessment results. RESULTS: The prevalence of EDs among 117 psychiatric inpatients was 9.4%, all were female and all diagnosed with unspecified feeding and eating disorder. We showed that 63.6% of patients with EDs was diagnosed after the screening and not with the routine clinical interview. EAT-26 scores were weakly correlated with affective (r = 0.314, p = .001), anxious (r = 0.231, p = .012), somatic (r = 0.258, p = .005), and impulsive maladaptive behaviours (r = 0.272, p = .003). A formal ED diagnosis was positively associated with media pressure, (OR:1.660, 95% CI: 1.105-2.495) and oppositional defiance (OR: 1.391, 95% CI: 1.005-1.926), and negatively with conduct problems (OR: 0.695, 95% CI: 0.500-0.964). The CDFRS results were not different between the ED and non-ED groups. CONCLUSIONS: Our study suggests EDs remain a prevalent yet often overlooked diagnosis in adolescent psychiatric inpatients. Health care providers should screen for EDs in inpatient psychiatric settings as a part of routine assessment to improve the identification of disordered eating behaviours that often begin during adolescence.

Brief report: how anxiously withdrawn preadolescents think about friendship.

Previous research suggests that anxiously withdrawn preadolescents demonstrate success in forming friendships, yet these friendships tend to be of lesser quality. Drawing on Selman's (1980) theory of interpersonal understanding, we compared levels of friendship understanding between anxiously withdrawn preadolescents and a sample of non-withdrawn age mates. Fifth graders (N = 116; 58% girls; mean age = 10.33 yrs) completed same-sex friendship and social behavior nominations, as well as a semi-structured clinical interview assessing understanding of various friendship issues in response to a hypothetical friendship dilemma. Results suggest that anxiously withdrawn preadolescents demonstrated lower levels of friendship understanding for some, but not all, friendship issues that may be related to friendship quality. The findings suggest that social cognitive assessments of friendship may be useful in understanding the friendship successes and difficulties of anxiously withdrawn preadolescents.

Brief report: engagement in sport and identity status.

Drawing on identity development theory, the connection between engagement in sport and identity status was examined. First-year undergraduates (n = 116 sport-involved youth; 67% women; mean age = 18.58 yrs) completed measures of interpersonal and ideological identity status (achievement, moratorium, diffusion, foreclosure), along with behavioral (breadth, intensity) and psychological (e.g., enjoyment, competence) indicators of sport engagement. Using structural equation modeling, we examined the relation between latent sport engagement and identity status in interpersonal and ideological domains. As hypothesized, latent sport engagement predicted greater interpersonal (but not ideological) identity achievement. Consistent with identity development theory, an additional specific relation was observed between lower breadth of sport involvement and higher interpersonal identity achievement. Results demonstrate the value of examining behavioral and psychological indicators of sport engagement jointly, and support a growing body of research linking sport and positive youth development.

A mathematical model of cartilage regeneration after chondrocyte and stem cell implantation - I: the effects of growth factors.

Autologous chondrocyte implantation is a cell-based therapy for treating chondral defects. The procedure begins by inserting chondrocytes into the defect region. The chondrocytes initiate healing by proliferating and depositing extracellular matrix, which allows them to migrate into the defect until it is completely filled with new cartilage. Mesenchymal stem cells can be used instead of chondrocytes with similar long-term results. The main differences are at early times since mesenchymal stem cells must first differentiate into chondrocytes before cartilage is formed. To better understand this repair process, we present a mathematical model of cartilage regeneration after cell therapy. We extend our previous work to include the cell-cell interaction between mesenchymal stem cells and chondrocytes via growth factors. Our results show that matrix formation is enhanced at early times in the presence of growth factors. This study reinforces the importance of mesenchymal stem cell and chondrocyte interaction in the cartilage healing process as hypothesised in experimental studies.

A mathematical model of cartilage regeneration after chondrocyte and stem cell implantation - II: the effects of co-implantation.

We present a mathematical model of cartilage regeneration after cell therapy, to show how co-implantation of stem cells (mesenchymal stem cells) and chondrocytes into a cartilage defect can impact chondral healing. The key mechanisms involved in the regeneration process are simulated by modelling cell proliferation, migration and differentiation, nutrient diffusion and Extracellular Matrix (ECM) synthesis at the defect site, both spatially and temporally. In addition, we model the interaction between mesenchymal stem cells and chondrocytes by including growth factors. In Part I of this work, we have shown that matrix formation was enhanced at early times when mesenchymal stem cell-to-chondrocyte interactions due to the effects of growth factors were considered. In this article, we show that the additional effect of co-implanting mesenchymal stem cells and chondrocytes further enhances matrix production within the first year in comparison to implanting only chondrocytes or only mesenchymal stem cells. This could potentially reduce healing time allowing the patient to become mobile sooner after surgery.

Does Love Influence Athletic Performance? The Perspectives of Olympic Athletes.

In this brief report, we provide an initial account of the association between love and athletic performance from the perspective of Olympic athletes. We posit that Romantic Passionate Love (RPL) and athletic performance may both involve the reward-motivation system of the brain. Based on this premise, we explored whether activation in one domain (love) might influence the other (sport). Our investigation was framed using Sternberg's triangular theory of love. Twenty Olympic athletes representing different sports were interviewed at the Games. Most athletes (n = 15) reported that their performance was better while in love; however, qualitative responses suggested that the benefits were correlated with rather than resulting from RPL. Although the athletes were provided with a definition of RPL and affirmed that their relationship met the criteria, interview responses reflected companionate rather than passionate love, suggesting that RPL may be differentially conceptualized across cultures. The study provides preliminary data that may be used to inform and refine future work on this topic.

Epidemiology of substance-exposed pregnancies at one Great Lakes hospital that serves a large number of American Indians.

OBJECTIVE: The purpose of this research was to determine the prevalence of substance-exposed pregnancies at a hospital in the Great Lakes region of the U.S. METHOD: Data were collected via retrospective chart abstractions of patients who were seen for delivery at one Great Lakes region hospital during a 1-year period who were given at least one of the International Classification of Diseases codes related to substance use. RESULTS: A total of 342 medical records were included in the analysis, and, while much race/ethnicity data were missing, a large percentage of those in our analysis identified as American Indian. The prevalence of substance-exposed pregnancies at this hospital during a 1-year period was 34.5%. The majority (84.8%) were tobacco users, and many were found to have multiple substance exposures. Also, 48.5% were found to have a mental health diagnosis in addition to substance use. CONCLUSIONS: Data from this project can be used in prevention efforts, including preconception care for women at risk for substance use and mental health issues.

Development of ambulatory arterio-venous carbon dioxide removal (AVCO2R): the downsized gas exchanger prototype for ambulation removes enough CO2 with low blood resistance.

We are developing an ultra compact gas exchanger to allow ambulation during arterial-venous CO2 removal (AVCO2R). The ambulatory AVCO2R gas exchanger (135 ml prime volume and 1.3 M2 gas exchange surface area) is made of polymethylpentene hollow fibers. The gas exchanger was attached to sheep carotid artery (12F) and jugular vein (14F) by percutaneous cannulae for 6 hours (n = 5). Device CO2 removal was measured and calculated at a constant blood flow rate of 1 L/min coupled with varying sweep gas from 1 to 15 L/min, and at constant sweep gas flow of 2 L/min coupled with varying blood flow from 0.5 to 1.25 L/min to determine capacity of CO2 removal at Pa CO2 = 40-50 mm Hg. Blood gases, CO2 removal and hemodynamics were recorded at 0, 3, and 6 hours. CO2 removal increased with sweep gas flow rate and with increase of device blood flow. Hemodynamics remained unchanged throughout study. Gas exchanger resistance remained stable at 2.3 +/- 0.53 mm Hg/L/min. CO2 removal with 1 L/min blood flow and 2 L/min sweep gas was 110 +/- 12 then stabilized at 85 +/- 14 mL/min to 6 hours. The compact ambulatory AVCO2R gas exchanger achieves stable, near total CO2 removal for at least 6 hours with a simple arteriovenous shunt.

Adolescent peer interaction and trait surgency weaken medial prefrontal cortex responses to failure.

Adolescent risk taking has been known to increase in the presence of peers. We hypothesized that peer interaction reduces the activation of the medial prefrontal cortex (mPFC) that is required for self-regulation of reward-driven behavior. We also expected that mPFC activity would be reduced more in those with greater surgency, a composite trait of behavioral approach, sensation seeking and positive affect. In our study, 20 15-year-old boys played a simulated driving video game alone and in the presence of peers who were encouraged to call out advice while we recorded the feedback-related negativity (FRN) event-related potential in response to an impending car crash. FRN amplitude was reduced both as a function of peer presence and increased surgency. More importantly, we also calculated intracerebral current source density at the time of the FRNs, and found that both greater surgency and peer presence are associated with reduced activity specifically in the mPFC. Riskier performance resulting in more car crashes resulted from the presence of peers only as an interaction with surgency, this interaction being related strongly to reduced activity in the ventromedial PFC.