Serum deprivation improves seeding and repopulation of acellular matrices with valvular interstitial cells

Cell-extracted valvular tissues (acellular scaffolds, or aScaffolds) offer unique advantages over synthetic polymers for cardiac valve engineering applications in that they retain extracellular matrix molecules to support cellular ingrowth. The extracellular matrix is important in directing many cellular pathways, such as adhesion, proliferation, migration, differentiation, and survival. However, repopulating this type of scaffold often requires high seeding densities or recurrent cell delivery. The optimization of valvular interstitial cell (VIC) seeding onto aScaffolds is reported herein. VICs (the most prevalent cell type in valve leaflets) have maximal growth in 15-20% serum concentrations on tissue-culture polystyrene. Interestingly, after VIC seeding onto aScaffolds, a reduction of serum content, from 15% serum to 5% or less, was found to increase significantly the number of adherent cells, as well as induce transfer of VICs from a tissue-culture polystyrene surface to the aScaffold. aScaffolds seeded and cultured with periods of reduced serum levels were shown to support and enhance VIC viability and attachment, as well as accelerate VIC migration into the aScaffold, leading to a uniformly repopulated valve leaflet construct after 4 weeks of static culture.     

Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.     

Identifying Opportunities to Improve Pain Among Patients With Serious Illness

Context

Pain is a common and distressing symptom. Pain management is a core competency for palliative care (PC) teams.

Depression or resilience? A participatory study to identify an appropriate assessment tool with Kanien’kéha (Mohawk) and Inuit in Quebec

Purpose

We present a study on selection of a psychometric scale to be clinically used among Indigenous people with depression. Our aim was to select a psychometric tool for cultural adaptation with Mohawk and Inuit in Quebec.

Methods

We selected three depression scales and three protective factor scales based on: strong validity for psychometric properties, evidence for good psychometric qualities across translations, avoidance of cognitively complex sentences, brevity, and clarity. We submitted the scales for consultation, and followed qualitative participatory methods with Mohawks of Kahnawake and Inuit from Nunavik living in an urban environment. We collected data through ten focus groups with advisory committees, and carried out a thematic analysis of the information.

Results

The advisory groups considered the measurement scales to be unsafe. The major components that hindered their acceptance were: numeric rating, self-evaluation (versus supportive interaction), and a focus on symptoms rather than supportive factors. The participants preferred the Growth and Empowerment Measure due to its empowering approach. They voiced that it is necessary to develop a culturally sensitive and safe tool which facilitates interactions between the person and the practitioner.

Conclusion

This project provides valuable information about the perspectives of local Indigenous peoples regarding mental health and factors of empowerment and resilience. The ideal tool should be flexible in terms of the content and its use as compared to the conventional psychometric strategies. A tool developed with the Indigenous perspective on wellbeing could be used in psychological and psychiatric intervention as well as in social and community services.

     

The development and validation of the hypertension evaluation of lifestyle and management knowledge scale

Hypertension knowledge is an integral component of the chronic care model. A valid scale to assess hypertension knowledge and self-management skills is needed. The hypertension evaluation of lifestyle and management (HELM) scale was developed as part of a community-based study designed to improve self-management of hypertension. Participants included 404 veterans with hypertension. Literature review and an expert panel were used to identify required skills. Items were generated and pilot tested in the target population. Validity was assessed through comparisons of performance with education, health numeracy, print numeracy, patient activation and self-efficacy, and hypertension control. The HELM knowledge scale had 14 items across 3 domains: general hypertension knowledge, lifestyle and medication management, and measurement and treatment goals. Scores were positively associated with education (0.28, P<.0001), print health literacy (0.21, P<.001), health numeracy (0.17, P<.001), and patient activation (0.12, P=.015) but no association was found with diastolic or systolic blood pressure. The HELM knowledge scores increased following the educational intervention from baseline (mean, 8.7; standard deviation, 2.2) to 12-month follow-up (mean, 9.2, standard deviation, 2.2; P<.001). We conclude that the HELM provides a valid measure of the knowledge required for patients to take an active role in the chronic disease management of hypertension.     

Evidence for behavioral sensitization to cocaine in preweanling rat pups

While chronic intermittent administration of stimulants often induces behavioral sensitization in adulthood, stimulant sensitization has rarely been reported prior to weaning [around postnatal day (P) 21]. Consistent pairing of drug administration with the test context often facilitates sensitization in adults, yet young animals have been typically returned to the home cage immediately post-injection. To determine whether promoting context-dependent sensitization might facilitate expression of sensitization in preweanlings, Sprague-Dawley rats were injected daily from P14 to P20 with 0, 5, 15, or 30 mg/kg cocaine HC1 and placed for 30 min in either the experimental chamber or home cage. On P21 (test day), subjects were challenged with either 15 mg/kg cocaine or saline prior to placement in the experimental chamber. Significant sensitization of cocaine-induced stereotyped head movements was evident in animals given 15 or 30 mg/kg chronically in the experimental chamber, but not when these same doses were given in the home cage. Less consistent evidence for cocaine-induced sensitization was seen when examining locomotion, although trends for sensitization of this behavior were seen in animals chronically injected in either the test chamber or home cage. Thus, preweanlings can exhibit cocaine sensitization, particularly in terms of stereotypy, when tested shortly after the chronic exposure period, with expression of this sensitization being facilitated by pairing the chronic injections with the test context. Received: 19 November 1996/Final version: 10 December 1997     

Promotion of healthy weights at preschool public health vaccination clinics in Calgary: an obesity surveillance program

OBJECTIVE: To evaluate the acceptability and feasibility of a surveillance program of overweight and obesity in preschool children in Calgary, and to provide advice for families to promote healthy weights. PARTICIPANTS AND SETTING: Children (mean age 4.9+/-0.6 years) attending pilot-site clinics in September 2002 and all clinics in Calgary between February 2003-December 2003 (n=7048). INTERVENTION: The growth assessment protocol and resources supported a three-pronged approach to promote healthy weights (healthy eating, active living and positive body image). Public health nurses were trained in standardized measurement techniques and information resources. Links with physicians were made to facilitate continuity of care. Children's weight and height measurements were plotted on the Weight-for-Stature growth chart and used to identify children as obese (> or =95th percentile), healthy weight (> or =5th, <95th) or underweight (<5th). Subsequent analysis calculated the Body Mass Index (BMI)-for-Age to identify overweight children (> or =85th, <95th percentile). The protocol was pilot tested and subsequently implemented in all Calgary public health clinics. OUTCOMES: The majority (98%) of parents were either very happy or happy with information received during the visit. Public health nurse counselling confidence significantly improved after the pilot (p<0.001). Data indicated that 9% of children were obese, 15% were overweight and 3% were underweight. INTERPRETATION: This approach to identifying children's weight status appeared satisfactory to stakeholders, maximized use of existing resources to establish a surveillance program for Calgary, and provided an opportunity to give parents health-promoting advice on healthy weights.     

Designing scaffolds for valvular interstitial cells: cell adhesion and function on naturally derived materials

Valvular interstitial cells (VICs) possess many properties that make them attractive for use in the construction of a tissue-engineered valve; however, we have found that the surfaces to which VICs will adhere and spread are limited. For example, VICs adhere and spread on collagen and laminin-coated surfaces, but display altered morphology and do not proliferate. Interestingly, fibronectin (FN) was one adhesion protein that facilitated VIC adhesion and proliferation. Yet VICs did not spread on surfaces modified with RGD, a ubiquitous cell-adhesive peptide, nor with other FN-specific peptide sequences such as EILDV and PHSRN. Hyaluronic acid (HA) is a highly elastic polysaccharide that is involved in natural valve morphogenesis and possesses binding interactions with FN. Hyaluronic acid was modified to form photopolymerizable hydrogels, and VICs were found to spread and proliferate on HA-based gels, forming a confluent monolayer on the gels within 4 days. Modified HA retained its ability to specifically bind FN, allowing for the formation of gels containing both HA and FN. Valvular interstital cells cultured on HA surfaces displayed significantly increased production of extracellular matrix proteins, indicating that HA-based scaffolds may provide useful biological cues to stimulate heart valve tissue formation.