Individual-level behavioral interventions to support optimal development of children with sickle cell disease: A systematic review

This review aimed to identify and describe individual-level behavioral interventions for children 0–18 years of age with sickle cell disease (SCD). PRISMA guidelines were followed at each stage of this review. Twenty-seven studies were included, representing six intervention types: disease knowledge (n = 7), self-management (n = 7), pain management (n = 4), school functioning (n = 4), cognitive health (n = 4), and mental health (n = 2). Most interventions targeted older children (5+ years), while only two examined interventions for children 0–3 years. This review suggests that offering education about disease knowledge, self-management, and pain management interventions can be beneficial for this population. Future research is needed to understand interventions to support young children and the impact of SCD on development.     

<Emphasis Type="Italic">FAM13A</Emphasis> and <Emphasis Type="Italic">POM121C</Emphasis> are candidate genes for fasting insulin: functional follow-up analysis of a genome-wide association study

Aims/hypothesis

By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs).

Methods

Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes.

Results

Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs3822072), the FSI-increasing allele associated with lower FAM13A expression and FAM13A expression associated with a beneficial metabolic profile including decreased WAT lipolysis (regression coefficient, R?=??0.50, p?=?5.6?×?10^?7). Knockdown of FAM13A increased lipolysis by ~1.5-fold and the expression of LIPE (encoding hormone-sensitive lipase, a rate-limiting enzyme in lipolysis). At the chromosome 7 locus (rs1167800), the FSI-increasing allele associated with lower POM121C expression. Consistent with an insulin-sensitising function, POM121C expression associated with systemic insulin sensitivity (R?=??0.22, p?=?2.0?×?10^?2), adipocyte insulin sensitivity (R?=?0.28, p?=?3.4?×?10^?3) and adipose hyperplasia (R?=??0.29, p?=?2.6?×?10^?2). POM121C knockdown decreased expression of all adipocyte-specific markers by 25–50%, suggesting that POM121C is necessary for adipogenesis.

Conclusions/interpretation

Gene expression and adipocyte functional studies support the notion that FAM13A and POM121C control adipocyte lipolysis and adipogenesis, respectively, and might thereby be involved in genetic control of systemic insulin sensitivity.

     

Intergenerational service-learning across levels and disciplines:"one size (does not) fit all"

Service-learning is increasingly becoming an avenue used in a variety of disciplines to provide students with real-life experience regarding aging and older adults. Developing and implementing meaningful service-learning experiences, however, requires consideration both of the discipline-specific content to be addressed, as well as the varied backgrounds (educational and personal) and levels (freshman to graduate) of the students who will be participating. Intergenerational service-learning is not a one-size-fits-all endeavor. Drawing on the experiences of intergenerational service-learning programs at three institutions (representing three disciplines-Gerontology, Nursing, and Occupational Therapy), this paper focuses on the discipline-specific challenges of building a quality intergenerational service-learning program, as well as the associated challenges of developing appropriate intergenerational service-learning experiences for a range of student levels with varied backgrounds.     

Self-Expandable nitinol stent for cardiovascular applications: canine and human experience

The initial experimental and clinical experience with the cardiovascular self-expandable Nitinol stent (vascular and coronary versions) is described. The stent is designed as a helical coil with two terminal balls that are used for restraining it on the delivery catheter. Upon release, the stent self-expands immediately. A temporary stent version continues with a long wire that can be removed by pulling it as a straight wire through a small profile catheter. The stent uncoils in its own groove upon removal, a relatively atraumatic procedure. The stents have been studied in dogs and in peripheral arteries in patients. The results show a transient nonocclusive proliferative response to the stent that is maximal at 3–6 mo. The removability of the permanent stent has been proven in dogs. The preliminary results in patients are encouraging and demonstrate its feasibility for permanent and potentially temporary arterial support. © 1994 Wiley-Liss,Inc..     

Implications of new petrographic analysis for the Olmec "mother culture" model

Petrographic analysis of Formative Mexican ceramics by J. B. Stoltman et al. (see the companion piece in this issue of PNAS) refutes a recent model of Olmec "one-way" trade. In this paper, we address the model's more fundamental problems of sampling bias, anthropological implausibility, and logical non sequiturs. No bridging argument exists to link motifs on pottery to the social, political, and religious institutions of the Olmec. In addition, the model of unreciprocated exchange is implausible, given everything that the anthropological and ethnohistoric records tell us about non-Western societies of that general sociopolitical level.     

Stakeholder involvement in the systematic optimisation of two school-based relationships and sex education interventions,Project Respect and Positive Choices

Background

There is increasing emphasis on involving intended beneficiaries and other stakeholders in the development of public health interventions to maximise acceptability and remove barriers to adoption, implementation, and maintenance before costly implementation. Yet the processes whereby key actors are engaged in intervention development are rarely reported, and frameworks for carrying out such work remain limited. We outline our approach to involving stakeholders in the optimisation of two school-based relationships and sex education programmes (Project Respect and Positive Choices) and reflect on the challenges of co-producing with teachers, students, and other partners.

Relationship between gastrointestinal and dysmenorrheic symptoms at menses

The relationship between gastrointestinal (GI) symptoms and uterine cramping pain at menses, controlling for affective states and prostaglandin synthesis inhibitor use, was examined. A total of 53 women completed a daily diary of symptoms, stool characteristics, and medication use for three consecutive menstrual cycles. There were significant across-women and within-woman relationships between stomach pain, nausea, and uterine cramping pain, but not between cramping pain and constipation, diarrhea, or stool characteristics. These results support the presence of a similar mechanism in the generation of distressing GI symptoms and uterine cramping pain at menses. © 1996 John Wiley & Sons, Inc.     

Disopyramide is an effective inhibitor of mutant HERG K+ channels involved in variant 1 short QT syndrome

The recently identified idiopathic short QT syndrome (SQTS) is associated with an increased risk of arrhythmia and sudden death. The use of implantable cardioverter defibrillators helps to protect SQTS patients from ventricular fibrillation; however, pharmacological treatments to normalise the QT interval are limited: thus far only quinidine has been found to be effective in a subset of patients, with the SQT1 variant. SQT1 is associated with an amino acid substitution (N588K) in the KCNH2-encoded HERG K(+) channel that reduces HERG current (I(HERG)) inactivation and sensitivity to drug block. We demonstrate here that the N588K-HERG mutation only slightly attenuates I(HERG) blockade by the Class Ia antiarrhythmic drug disopyramide (1.5-fold elevation of IC(50)), compared to quinidine (3.5-fold elevation of IC(50)) and the Class III antiarrhythmic drug E-4031 (11.5-fold elevation of IC(50)). Thus, of the drugs studied to date, disopyramide is the one least affected by the SQT1 HERG mutation. Disopyramide is associated with QT prolongation in normal use and our findings provide a rational basis for its evaluation as a treatment for SQT1.