Comparison of Two Brief Parent-Training Interventions for Child Distress During Parent-Administered Needle Procedures

This randomized clinical trial employed a 2-group (general child behavior management training vs. distraction for pain management training) design across repeated parent-administered needle procedures. Forty-seven children with a chronic illness requiring recurrent injections were observed at baseline and 2 intervention sessions. Videotaped observations of parent–child interactions were coded for child behavioral distress and parents' use of behavior management strategies. Across groups, many children displayed minimal to no distress at baseline. Among participants with significant distress, neither intervention group displayed consistently decreased procedural distress or increased use of child behavior management strategies.     

Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors

Objective: To determine the effects of maternal citrulline supplementation on fetal growth and placental efficiency in a rat model of intrauterine growth restriction (IUGR) induced by maternal protein restriction.

Methods: Pregnant Sprague–Dawley rats were randomly assigned to three groups: NP (receiving a control 20% protein diet), LP (a 4% protein diet), or LP-CIT (an LP diet along with L-citrulline, 2?g/kg/d in drinking water). On the 15th and 21st day of gestation (GD15 and GD21, respectively), dams underwent a C-section, by which fetuses and placentas were extracted. The expression of genes involved in placental growth and angiogenesis was studied by quantitative RT-PCR.

Results: Maternal citrulline supplementation increased fetal weight at GD21, and fetal weight/placental weight ratio, an index of placental efficiency, from mid gestation (p?Igf2-P0, a placenta-specific variant of insulin-like growth factor 2 (Igf2) gene, and Vegf and Flt-1, involved in angiogenic pathways, was enhanced in the LP-CIT group (versus NP, p?p?p?Igf2-P0, Vegf, and Flt-1, respectively).

Conclusions: In a model of IUGR induced by protein deprivation, citrulline enhances fetal growth, placental efficiency, and the expression of genes involved in angiogenesis. The relevance of such effect in human pregnancies complicated by IUGR warrants further study.     

Broad human immunodeficiency virus (HIV)-specific T cell responses to conserved HIV proteins in HIV-seronegative women highly exposed to a single HIV-infected partner

Eighteen highly exposed but persistently seronegative (HEPS) women (HW) and their human immunodeficiency virus (HIV) type 1-seropositive male partners were studied for HIV-specific T cells and other host factors. Circulating HIV-specific T cells were measured by interferon-gamma enzyme-linked immunospot assays, using recombinant vaccinia virus vectors expressing HIV proteins. Nine (50%) of the HW and all HIV-seropositive persons had HIV-specific T cell responses. Only 2 (22%) of the HEPS responders recognized Env, compared with 94% of HIV-seropositive persons. A high percentage (75%) of the HW with HIV-specific T cell responses reported recent HIV exposure. Remarkably, however, long-lived HIV-specific T cells were detected in 2 HW who had an extended period (>3.9 years) of no HIV exposure. These findings have important implications for HIV vaccine design.     

Efficient and non-toxic gene transfer to cardiomyocytes using novel generation amplicon vectors derived from HSV-1

OBJECTIVE: The feasibility of gene transfer to myocardial tissue using viral vectors was investigated over the last few years. In this study we report gene transfer using a recently described improved of Herpes simplex virus (HSV-1)-derived amplicon vectors and demonstrate that these vectors are a powerful and potentially very interesting tool for gene transfer into neonatal primary as well as in adult cardiac myocytes. METHODS AND RESULTS: Non-pathogenic HSV-1 amplicon vectors simultaneously expressing GFP and LacZ were constructed using a novel helper system that yields essentially helper-free vector particles. These vectors were used to infect either cultured primary neonatal rat cardiomyocytes or adult cardiac tissue. Transgenic expression was quantified using a FACS (GFP) or X-gal staining (LacZ). Infection of primary cardiomyocytes showed efficient transduction even at very low multiplicity of infection (MOI), and expression increased with the infectious dose. By investigating release of lactate dehydrogenase (LDH) or spontaneous beating of the cells, we failed to detect cytotoxic effects in cardiomyocytes infected at high MOI. Thin slices of adult cardiac tissue placed in medium containing vectors also showed very good levels of transduction, without any evidence of toxic effects. CONCLUSIONS: Helper-free amplicon vectors very efficiently transduce genes into cardiomyocytes. Our results indicate similar or better transduction efficiencies than those reported using other vector systems. Furthermore, the very high transgenic capacity of amplicon vectors (up to 150 kbp) makes these vectors a unique and very suitable system to transduce large genomic sequences into cardiomyocytes.     

Validating the International Classification of Functioning, Disability and Health Comprehensive Core Set for Rheumatoid Arthritis from the patient perspective: a qualitative study

OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for Rheumatoid Arthritis (RA) from the patient perspective. METHODS: Patients with RA were interviewed about their problems in daily functioning. Interviews were tape recorded and transcribed verbatim. Interview texts were divided into meaning units. The concepts contained in these meaning units were linked to the ICF according to 10 established linking rules. Of the transcribed data, 15% were analyzed and linked by a second health professional. The degree of agreement was calculated using the kappa statistic. RESULTS: Twenty-one patients were interviewed. Two hundred twenty different concepts contained in 367 meaning units were identified in the qualitative analysis of the interviews and linked to 109 second-level ICF categories. Of the 76 second-level categories from the ICF RA Core Set, 63 (83%) were also found in the interviews. Twenty-five second-level categories, which are not part of the current ICF RA Core Set, were identified in the interviews. The result of the kappa statistic for agreement was 0.62 (95% boot-strapped confidence interval 0.59-0.66). CONCLUSION: The validity of the ICF RA Core Set was supported by the perspective of individual patients. However, some additional issues raised in this study but not covered in the current ICF RA Core Set need to be investigated.     

Characterization of a possible amyloidogenic precursor in glutamine-repeat neurodegenerative diseases

Several neurodegenerative diseases are linked to expanded repeats of glutamine residues, which lead to the formation of amyloid fibrils and neuronal death. The length of the repeats correlates with the onset of Huntington's disease, such that healthy individuals have <38 residues and individuals with >38 repeats exhibit symptoms. Because it is difficult to obtain atomic-resolution structural information for poly(l-glutamine) (polyQ) in aqueous solution experimentally, we performed molecular dynamics simulations to investigate the conformational behavior of this homopolymer. In simulations of 20-, 40-, and 80-mer polyQ, we observed the formation of the "alpha-extended chain" conformation, which is characterized by alternating residues in the alpha(L) and alpha(R) conformations to yield a sheet. The structural transition from disordered random-coil conformations to the alpha-extended chain conformation exhibits modest length and temperature dependence, in agreement with the experimental observation that aggregation depends on length and temperature. We propose that fibril formation in polyQ may occur through an alpha-sheet structure, which was proposed by Pauling and Corey. Also, we propose an atomic-resolution model of how the inhibitory peptide QBP1 (polyQ-binding peptide 1) may bind to polyQ in an alpha-extended chain conformation to inhibit fibril formation.     

Safety and tolerability of oral daily and intermittent ibandronate are not influenced by age

OBJECTIVE: The risk of osteoporosis increases exponentially with age. Elderly patients, who are often frail, have declining functional status and take multiple medications, and require osteoporosis therapies that are not only effective, but also very well tolerated. Ibandronate is a potent nitrogen-containing bisphosphonate that can be given intermittently with extended between-dose intervals. Oral daily and intermittent ibandronate (interval between doses > 2 mo) was found to significantly reduce the risk of new morphometric vertebral fractures by 62% and 50%, respectively, compared with calcium and vitamin D supplementation alone. We investigated the effect of age on the safety profile of oral daily and intermittent ibandronate, with particular emphasis on the upper gastrointestinal (GI) safety profile of ibandronate. METHODS: A predefined subgroup analysis examined the tolerability of oral ibandronate in women aged < 70 and > or = 70 years. RESULTS: The incidence of adverse events in patients aged > or = 70 years receiving oral daily and intermittent ibandronate was similar and comparable to placebo. The incidence of upper GI adverse events, including dyspepsia and esophagitis, was also similar between the 2 treatment groups and placebo. CONCLUSION: Older patients (> or = 70 yrs) receiving oral daily and intermittent ibandronate are at no greater risk of adverse events than older patients receiving placebo. Older patients were at no greater risk of upper GI adverse events than younger patients or patients receiving placebo. As a result of the good efficacy and tolerability observed in this trial, a once-monthly oral regimen of ibandronate is in late-stage clinical development.