Measuring Pectus Excavatum Severity, External Caliper, or Cross-Sectional Imaging: Family Perceptions.

INTRODUCTION: Patients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs. METHODS: This is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05. RESULTS: There were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04). CONCLUSIONS: From the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE.

Statin treatment reduces leucine turnover, but does not affect endogenous production of beta-hydroxy-beta-methylbutyrate (HMB).

BACKGROUND: Statins, or hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, are one of the most commonly prescribed medications for lowering cholesterol. Myopathic side-effects ranging from pain and soreness to critical rhabdomyolysis are commonly reported and often lead to discontinuation. The pathophysiological mechanism is, in general, ascribed to a downstream reduction of Coenzyme Q10 synthesis. HMG-CoA is a metabolite of leucine and its corresponding keto acid α-ketoisocaproic acid (KIC) and ß-hydroxy-ß-methylbutyrate (HMB), however, little is known about the changes in the metabolism of leucine and its metabolites in response to statins. OBJECTIVE: We aimed to investigate if statin treatment has implications on the upstream metabolism of leucine to KIC and HMB, as well as on other branched chain amino acids (BCAA). DESIGN: 12 hyperlipidemic older adults under statin treatment were recruited. The study was conducted as a paired prospective study. Included participants discontinued their statin treatment for 4 weeks before they returned for baseline measurements (before). Statin treatment was then reintroduced, and the participants returned for a second study day 7 days after reintroduction (after statin). On study days, participants were injected with stable isotope pulses for measurement of the whole-body production (WBP) of all BCAA (leucine, isoleucine and valine), along with their respective keto acids and HMB. RESULTS: We found a reduced leucine WBP (22 %, p = 0.0033), along with a reduction in valine WBP (13 %, p = 0.0224). All other WBP of BCAA and keto acids were unchanged. There were no changes in the WBP of HMB. CONCLUSIONS: Our study shows that statin inhibition of HMG-CoA reductase has an upstream impact on the turnover of leucine and valine. Whether this impairment in WBP of leucine may contribute to the known pathophysiological side effects of statins on muscle remains to be further investigated.

A pilot randomized trial of the body advocacy movement: a novel, dissonance-based intervention designed to target fear of weight gain and anti-fat bias in young adults.

The Body Advocacy Movement (BAM) is a novel, cognitive-dissonance-based intervention designed to target fatphobia and anti-fat bias as mechanisms to drive reductions in eating disorder (ED) risk. Previous dissonance-based programs (i.e. the Body Project; BP) have successfully targeted thin-ideal internalization as an intervention mechanism. As burgeoning research indicates that fatphobia and anti-fat bias may play a central role in the maintenance of ED pathology, a focused intervention designed to target these constructs could bolster prevention efforts. The aims of this pilot study include confirming acceptability and feasibility of BAM and developing preliminary estimates of its effects on intervention targets, along with benchmarking these effects against the BP intervention. BAM was found to be accepted by participants and feasible to facilitate in a peer-led model. Preliminary results from 50 participants (BAM: N = 26; BP: N = 24) reveal small-to-moderate pre-to-post intervention effects on fatphobia, anti-fat bias, thin-ideal internalization, and eating pathology, which dissipated at 8-week follow-up. The BAM intervention has the potential to supplement the existing suite of ED prevention programs by specifically targeting anti-fat bias, though additional testing in larger and more diverse samples is necessary to clarify its impact on both hypothesized risk mechanisms and ED outcomes.

Perceptions of employability related to severity of hypernasality: a pilot study.

The primary aim of this investigation was to evaluate listener auditory-perceptual assessment of employability for individuals with hypernasal speech. Using an online survey platform, listeners with managerial experience evaluated speech samples from individuals with varying hypernasal resonance disorder severity to determine auditory-perceptual judgements regarding intelligence and employability. Speech samples of individuals with hypernasal speech were rated lower on scales of intelligence and employability, and more likely to be selected for jobs with infrequent rates of communication and lower levels of responsibility. Additionally, males with hypernasal speech were perceived as less intelligent, less employable, and more likely to be selected for a job with infrequent communication in comparison to females with hypernasal speech. Results of this preliminary investigation suggest that individuals with hypernasal speech may face employment barriers. The conclusions collected from this initial investigation open the doors for further research addressing linguistic considerations and aspects of employability. This is an important consideration for individuals with either acquired or congenitally related hypernasal resonance disorder.

An In Vitro Characterization of a PCL-Fibrin Scaffold for Myocardial Repair.

Each year in the United States approximately 10,000 babies are born with a complex congenital heart defect (CHD) requiring surgery in the first year of after birth. Several of these operations require the implantation of a full-thickness heart patch; however, the current patch materials available to pediatric heart surgeons are exclusively non-living and non-degradable, which do not grow with the patient and are prone to fail due to an inability to integrate with the heart. In this work, the goal was to develop a full-thickness, tissue engineered myocardial patch (TEMP) that is made from biodegradable components, strong enough to withstand the mechanical forces of the heart wall, and able to integrate with the heart and drive neotissue formation. Here, a thick and porous electrospun PCL scaffold filled with high-salt PEGylated fibrin was developed. The scaffold was found to be mechanically sufficient for heart wall repair. Vascular cells were able to infiltrate more than halfway through the scaffold in static culture within three weeks. The scaffold maintained pluripotent stem cells for at least four days, supports viable iPSC-derived cardiomyocytes, and fostered tissue thickening in vitro. The TEMP developed here and tested in vitro is promising for the repair of structural CHD and will next be assessed in situ.

Bioreactor Design for Culturing Vascularized Engineered Tissue in Flow Conditions.

BACKGROUND: Current treatments for congenital heart defects often require surgery and implantation of a synthetic patch or baffle that becomes a fibrous scar and leads to a high number of reoperations. Previous studies in rats have shown that a pre-vascularized scaffold can integrate into the heart and result in regions of vascularized and muscularized tissue. However, increasing the thickness of this scaffold for use in human hearts requires a method to populate the thick scaffold and mature it under physiologic flow and electrical conditions. EXPERIMENT: We developed a bioreactor system that can perfuse up to six 7-mm porous scaffolds with tunable gravity-mediated flow and chronic electrical stimulation. Three polymers which have been reported to be biocompatible were evaluated for effects on the viability of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM). Bioreactor flow and electrical stimulation functions were tested, and the bioreactor was operated for up to 7 days to ensure reliability and lack of leaks in a 37C, humidified incubator. Height and flow relationships were measured for perfusion through an electrospun polycaprolactone (PCL) and gelatin scaffold previously reported by our laboratory. Culture with cells was evaluated by plating human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (hDF) on top of the scaffolds in both static and flow conditions for 2,5 and 7 days. As a proof-of concept, scaffolds were cryosectioned and cell infiltration was quantified using immunofluorescence staining. RESULTS: Neither MED610 (Stratasys), Vero (Stratasys), nor FORMLAB materials affected the viability of iPSC derived cardiomyocytes, and MED610 was chosen for manufacture due to familiarity of 3D printing from this material. The generation of electrical field stimulation from 0 to 5 volts and physiological ranges of pump capacities were verified. The relationship between height and flow was calculated for scaffolds with and without cells. Finally, we demonstrated evaluation of cell depth and structure in scaffolds cultured for 2, 5, and 7 days. CONCLUSION: The gravity-mediated flow bioreactor system we developed can be used as a platform for 3D cell culture particularly designed for perfusing vascularized tissue constructs with electrical stimulation for cardiac maturation.

Consequences of PDGFRα+ fibroblast reduction in adult murine hearts.

Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. Although fibrosis accompanies many cardiac pathologies and is generally deleterious, the role of fibroblasts in maintaining the basal ECM network and in fibrosis in vivo is poorly understood. We genetically ablated fibroblasts in mice to evaluate the impact on homeostasis of adult ECM and cardiac function after injury. Fibroblast-ablated mice demonstrated a substantive reduction in cardiac fibroblasts, but fibrillar collagen and the ECM proteome were not overtly altered when evaluated by quantitative mass spectrometry and N-terminomics. However, the distribution and quantity of collagen VI, microfibrillar collagen that forms an open network with the basement membrane, was reduced. In fibroblast-ablated mice, cardiac function was better preserved following angiotensin II/phenylephrine (AngII/PE)-induced fibrosis and myocardial infarction (MI). Analysis of cardiomyocyte function demonstrated altered sarcomere shortening and slowed calcium decline in both uninjured and AngII/PE-infused fibroblast-ablated mice. After MI, the residual resident fibroblasts responded to injury, albeit with reduced proliferation and numbers immediately after injury. These results indicate that the adult mouse heart tolerates a significant degree of fibroblast loss with a potentially beneficial impact on cardiac function after injury. The cardioprotective effect of controlled fibroblast reduction may have therapeutic value in heart disease.

Supporting the Transition to Postsecondary Institutions for Students with Mental Health Conditions: A Scoping Review.

Objective: To conduct a scoping review to identify programs and interventions to support youth with mental health conditions (MHCs) with their transition to postsecondary institution (PSI). Method: A database search of MEDLINE, PsycINFO, Embase, SocINDEX, ERIC, CINHAL, and Education Research Complete was undertaken. In this review, MHC was defined as a mental, behavioural, or emotional condition, or problematic substance use, and excluded neurodevelopmental or physical disorders. Two reviewers independently screened studies and extracted the data. Included studies are described and a risk-of-bias assessment was conducted on included studies. Results: Nine studies were included in this review, describing eight unique interventions. Sixty-two percent of interventions were nonspecific in the MHCs that they were addressing in postsecondary students. These interventions were designed to support students upon arrival to their PSIs. Peer mentorship, student engagement, goal setting, and interagency collaboration were some of the strategies employed. However, the overall quality and level of evidence in these studies was low and the effectiveness of these programs was not established. Conclusion: The volume of research identified was limited, no reliable nor policy informing conclusions can yet be made about the impact of these interventions as the evaluation methods, quality of the research methodologies, and the levels of evidence available were of low-quality. Future randomized control trials are required that are designed to target and improve transitions from secondary education to PSIs for those with MHCs.

Objectif: Mener une étude de la portée afin d'identifier les programmes et interventions qui soutiennent les jeunes souffrant de troubles de santé mentale (TSM) dans leur transition à une institution post-secondaire (IPS). Méthode: Une recherche des bases de données MEDLINE, PsycINFO, Embase, SocINDEX, ERIC, CINHAL, et Education Research Complete a été entreprise. Dans cette revue, les TSM étaient définis comme un trouble mental, comportemental ou émotionnel, ou une utilisation de substances problématique et excluaient les troubles neurodéveloppementaux ou physiques. Deux réviseurs ont examiné indépendamment les études et extrait les données. Les études incluses sont décrites et une évaluation du risque de biais a été menée sur les études incluses. Résultats: Neuf études ont été incluses dans cette revue, qui décrivaient huit interventions uniques. Soixante-deux pour cent des interventions étaient non spécifiques dans les TSM qu'ils abordaient chez les élèves du post-secondaire. Ces interventions étaient conçues pour soutenir les élèves à leur arrivée à leur IPS. Le mentorat par les pairs, l'engagement des élèves, l'établissement de buts, et la collaboration inter-agence étaient certaines des stratégies employées. Toutefois, la qualité globale et le niveau des données probantes de ces études étaient faibles et l'efficacité de ces programmes n'a pas été établie. Conclusion: Le volume de recherche identifié était limité, rien de fiable ni aucune politique éclairant les conclusions ne peut encore révéler l'impact de ces interventions comme méthodes d'évaluation, la qualité des méthodologies de recherche, et les niveaux des données probantes disponibles étaient de faible qualité. Il faut de futurs essais randomisés contrôlés qui sont conçus pour cibler et améliorer les transitions de l'éducation secondaire aux IPS pour ceux qui souffrent de TSM.

A Prevascularized Polyurethane-Reinforced Fibrin Patch Improves Regenerative Remodeling in a Rat Right Ventricle Replacement Model.

Congenital heart defects (CHDs) affect 1 in 120 newborns in the United States. Surgical repair of structural heart defects often leads to arrhythmia and increased risk of heart failure. The laboratory has previously developed an acellular fibrin patch reinforced with a biodegradable poly(ether ester urethane) urea mesh that result in improved heart function when tested in a rat right ventricle wall replacement model compared to fixed pericardium. However, this patch does not drive significant neotissue formation. The patch materials are modified here and this patch is prevascularized with human umbilical vein endothelial cells and c-Kit+ human amniotic fluid stem cells. Rudimentary capillary-like networks form in the fibrin after culture of cell-encapsulated patches for 3 d in vitro. Prevascularized patches and noncell loaded patch controls are implanted onto full-thickness heart wall defects created in the right ventricle of athymic nude rats. Two months after surgery, defect repair with prevascularized patches results in improved heart function and the patched heart area exhibited greater vascularization and muscularization, less fibrosis, and increased M2 macrophage infiltration compared to acellular patches.

Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering.

Fibrin has been used clinically for wound coverings, surgical glues, and cell delivery because of its affordability, cytocompatibility, and ability to modulate angiogenesis and inflammation. However, its rapid degradation rate has limited its usefulness as a scaffold for 3D cell culture and tissue engineering. Previous studies have sought to slow the degradation rate of fibrin with the addition of proteolysis inhibitors or synthetic crosslinkers that require multiple functionalization or polymerization steps. These strategies are difficult to implement in vivo and introduce increased complexity, both of which hinder the use of fibrin in research and medicine. Previously, we demonstrated that additional crosslinking of fibrin gels using bifunctionalized poly(ethylene glycol)-n-hydroxysuccinimide (PEG-NHS) slows the degradation rate of fibrin. In this study, we aimed to further improve the longevity of these PEG-fibrin gels such that they could be used for tissue engineering in vitro or in situ without the need for proteolysis inhibitors. It is well documented that increasing the salinity of fibrin precursor solutions affects the resulting gel morphology. Here, we investigated whether this altered morphology influences the fibrin degradation rate. Increasing the final sodium chloride (NaCl) concentration from 145 mM (physiologic level) to 250 mM resulted in fine, transparent high-salt (HS) fibrin gels that degrade 2-3 times slower than coarse, opaque physiologic-salt (PS) fibrin gels both in vitro (when treated with proteases and when seeded with amniotic fluid stem cells) and in vivo (when injected subcutaneously into mice). Increased salt concentrations did not affect the viability of encapsulated cells, the ability of encapsulated endothelial cells to form rudimentary capillary networks, or the ability of the gels to maintain induced pluripotent stem cells. Finally, when implanted subcutaneously, PS gels degraded completely within one week while HS gels remained stable and maintained viability of seeded dermal fibroblasts. To our knowledge, this is the simplest method reported for the fabrication of fibrin gels with tunable degradation properties and will be useful for implementing fibrin gels in a wide range of research and clinical applications.