The hypospadias-specific health-related quality of life conceptual framework: a scoping review of the literature.

PURPOSE: Health-related quality of life (HRQoL) is an important yet understudied construct for individuals with hypospadias (HS). An important barrier towards understanding HRQoL and integrating it into research and clinical care for people with HS is the absence of an underlying conceptual framework to illustrate this construct. We propose a conceptual framework for HS-specific HRQoL based upon a scoping review of the HS literature. METHODS/MATERIALS: We conducted a literature review of articles published between 1989 and 2019. Our search in Embase and Pubmed used the keyword "hypospadias" in combination with "quality of life" and "patient-reported outcomes." We used thematic analysis of the resulting publications to identify core HRQOL domains. From these results and review of HRQoL literature in other pediatric populations, we developed a conceptual framework representing HS-specific HRQoL. RESULTS: We identified five domains of HRQOL previously studied in research with youth and adults with HS: penile appearance, voiding, social interaction, sexual health, and psychological or behavioral function. We propose a model of HS-specific HRQoL comprised of these domains and their areas of overlap, based upon the findings and conceptual mapping of our literature review. CONCLUSION: This novel conceptual framework provides a foundation for understanding disease-specific HRQoL in individuals with HS and may serve as a guide for the conduct of future qualitative studies of the HS population. The overlapping biopsychosocial domains illustrate the possible effects of HS on day-to-day life. This framework may guide future surgical, clinical, and behavioral interventions that aim to improve medical care and quality of life outcomes for HS patients.

Evaluating quality of patient-reported outcome measures in patients with hypospadias.

INTRODUCTION: There is growing recognition of the importance of patient-reported outcomes (PROs) in pediatric hypospadias. We have previously presented a conceptual framework for Hypospadias-Specific Health-Related Quality of Life (HRQoL), which posited 5 domains of HRQoL in this population. The framework components (domains) included penile appearance, voiding function, social function, psychological/behavioral function, and pubertal/sexual health. In this work, we investigated the established validity and relevance of PROs within each of these domains for patients with hypospadias. MATERIALS AND METHODS: We evaluated existing measures with published psychometric data, including validation data, in the hypospadias population. We also assessed the available data on each measure according to the guidelines of the Scientific Advisory Committee of the Medical Outcomes Trust (Table) in order to establish measure quality. We also examined the power of existing validation studies according to suggested guidelines for psychometric validation and factor analysis. DISCUSSION: Available validated measures in the hypospadias population have focused primarily on penile appearance and to a lesser degree on pubertal development/sexual health. There were no validated disease-specific measures with dedicated evaluations of other key HRQoL domains including voiding-related sequelae, social function, or psychological function. In addition, no single measure addressed all of the quality guidelines posed by the Scientific Advisory Committee. CONCLUSIONS: Current generalized measures for PROs lack relevance to the experience of hypospadias patients, and disease-specific assessments are often focused on penile appearance. Improving measure quality is necessary to optimize the value of our assessments and better help our patients with hypospadias.

Time spent outside of target glucose range for young children with type 1 diabetes: a continuous glucose monitor study.

AIM: To assess the associations between demographic and clinical characteristics and sensor glucose metrics in young children with type 1 diabetes, using masked, continuous glucose monitoring data from children aged 2 to < 8 years. RESEARCH DESIGN AND METHODS: The analysis included 143 children across 14 sites in the USA, enrolled in a separate clinical trial. Eligibility criteria were: age 2 to <8 years; type 1 diabetes duration ≥3 months; no continuous glucose monitoring use for past 30 days; and HbA1c concentration 53 to <86 mmol/mol (7.0 to <10.0%). All participants wore masked continuous glucose monitors up to 14 days. RESULTS: On average, participants spent the majority (13 h) of the day in hyperglycaemia (>10.0 mmol/l) and a median of ~1 h/day in hypoglycaemia (<3.9 mmol/l). Participants with minority race/ethnicity and higher parent education levels spent more time in target range, 3.9-10.0 mmol/l, and less time in hyperglycaemia. More time in hypoglycaemia was associated with minority race/ethnicity and younger age at diagnosis. Continuous glucose monitoring metrics were similar in pump and injection users. CONCLUSIONS: Given that both hypo- and hyperglycaemia negatively impact neurocognitive development, strategies to increase time in target glucose range for young children are needed.

Global proteomic characterization of uterine histotroph recovered from beef heifers yielding good quality and degenerate day 7 embryos.

The objective was to analyze the proteomic composition of uterine flushes collected from beef heifers on day 7 after insemination. Estrus was synchronized in crossbred beef heifers by using a protocol with a controlled intravaginal drug releasing device. Heifers detected in standing estrus (within 24-48 h after removal of controlled intravaginal drug releasing device) were inseminated (estrus = day 0) with frozen-thawed semen from a single ejaculate of a bull with proven fertility. Heifers from which an embryo was recovered (after slaughter on day 7) were classified as either having a viable embryo (morula/blastocyst stage) or a degenerate embryo (arrested at the 2- to 16-cell stage). The overall recovery rate (viable and degenerate combined) was 64%. Global liquid chromatography coupled to tandem mass spectrometry proteomic analysis of the histotroph collected identified 40 high-confidence proteins present on day 7; 26 proteins in the viable group, 10 in the degenerate group, and 4 shared between both groups. Five proteins (platelet-activating factor acetylhydrolase IB subunit γ [PAFAH1B3], tubulin α-1D chain, tubulin ß-4A chain, cytochrome C, and dihydropyrimidinase-related protein-2) were unique or more abundant in the histotroph collected from animals with a viable embryo, and 1 protein (S100-A4) was more abundant in the histotroph collected from animals with a degenerate embryo. Of interest, PAFAH1B3, detected only in histotroph from the group yielding viable embryos, belongs to the group of platelet-activating factors that are known to be important for the development of the pre-implantation embryo in other species. To our knowledge this is the first report of PAFAH1B3 in relation to bovine early embryonic development.

Family involvement with the diabetes regimen in young people: the role of adolescent depressive symptoms.

AIMS: In young people with Type 1 diabetes, depressive symptoms and shared responsibility for management of diabetes impact upon diabetes management and control. However, the simultaneous effects of both depressive symptoms and parental involvement on diabetes self-care and glycaemic control have not been examined. Thus, the aim of the current study was to examine the relationships between parental involvement and adolescent depressive symptoms in predicting blood glucose monitoring and glycaemic control. METHODS: One hundred and fifty young people with Type 1 diabetes (mean age 15.3 years) and their parents completed responsibility sharing and depressive symptom assessments, meter assessment of blood glucose monitoring and HbA(1c) at baseline and then 6, 12 and 18 months. RESULTS: Parental involvement affected HbA1c through blood glucose monitoring only at low levels of adolescent depressive symptoms (score ≤ 6), which made up only 20% of the sample. In the presence of more depressive symptoms, parental involvement no longer was related to HbA1c through blood glucose monitoring. This was the relationship in the majority of the sample (80%). CONCLUSIONS: While most young people in this sample are not showing evidence of high levels of depressive symptoms, even modest levels of distress interfere with parental involvement in diabetes management. By addressing adolescent depressive symptoms, interventions promoting parental involvement in these families may be more effective.

Parent stress and child behaviour among young children with type 1 diabetes.

BACKGROUND: Parents of young children with type 1 diabetes (T1D) are responsible for executing a complex daily management regimen and are at risk for elevated levels of stress. Normative misbehaviour during the preschool years can complicate T1D management, and interpretation of behavioural concerns may vary because of child health status and parent stress. Within a paediatric transactional model framework, child characteristics (e.g. behaviour problems, metabolic control) and parent functioning (e.g. parenting stress, anxiety) likely impact one another. METHODS: Parents of 2- to 6-year-old children with T1D completed self-report measures, including the Pediatric Inventory for Parents (PIP), State-Trait Anxiety Inventory (STAI), Eyberg Child Behavior Inventory (ECBI), and 24-h Recall Interviews. Medical data were obtained by parent report and medical record review. It was hypothesized that greater parent stress and child blood glucose variability would be significantly associated with greater parent-reported child behaviour concerns. RESULTS: Moderate levels of parent stress and child behaviour problems were endorsed; however, parents perceived children's misbehaviour as problematic, particularly with relation to tasks relevant to diabetes management (e.g. bedtimes and mealtimes). Structural equation modelling indicated that greater general anxiety and paediatric parenting stress was associated with parent report of more problematic child behaviour. Blood glucose variability did not significantly contribute to this relationship. CONCLUSIONS: The stress experienced by parents of young children with chronic illness appears to relate to their perception of their children's behaviour problems. Parents' experiences with developmentally normative misbehaviour may interfere with disease management and exacerbate parents' stress and the subsequent impact on well-being. Implications for supporting parents and children with T1D are discussed.

Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish?

While the research community has accepted the value of rodent models as informative research platforms, there is less awareness of the utility of other small vertebrate and invertebrate animal models. Neuroscience is increasingly turning to smaller, non-rodent models to understand mechanisms related to neuropsychiatric disorders. Although they can never replace clinical research, there is much to be learnt from 'small brains'. In particular, these species can offer flexible genetic 'tool kits' that can be used to explore the expression and function of candidate genes in different brain regions. Very small animals also offer efficiencies with respect to high-throughput screening programs. This review provides a concise overview of the utility of models based on worm, fruit fly, honeybee and zebrafish. Although these species may have small brains, they offer the neuropsychiatric research community opportunities to explore some of the most important research questions in our field.

Mechanism of basic calcium phosphate crystal-stimulated cyclo-oxygenase-1 up-regulation in osteoarthritic synovial fibroblasts.

OBJECTIVES: Basic calcium phosphate (BCP) crystals have been implicated in the pathogenesis of OA and stimulate cyclo-oxygenase (COX) expression and PGE(2) production. This study aimed to elucidate the mechanism of COX-1 up-regulation by BCP crystals and to characterize the PGs produced in OA synovial fibroblasts (OASFs) in response to BCP crystals. METHODS: OASFs were stimulated with BCP crystals in vitro. mRNA expression was measured by real-time PCR, PG production by EIA and protein production by western blot. RESULTS: Maximal (19-fold) up-regulation of COX-1 mRNA occurred 32 h after stimulation with BCP crystals; increased COX-1 protein production was also seen. At 32 h post-stimulation with BCP crystals, PGE(2) (and prostacyclin) production was COX-1 dependent. In contrast, maximal (17-fold) up-regulation of COX-2, with corresponding COX-2-dependent PG production, occurred 4 h after BCP crystal stimulation. There was no appreciable increased production of other PGs such as PGF(2alpha), thromboxane A(2) or cyclopentanone PGs including 15d-PGJ(2). Inhibition of protein kinase C (PKC) and extracellular regulated kinase 1/2 (ERK1/2) signal transduction pathways blocked BCP crystal-induced COX-1 mRNA expression. Bafilomycin A1, an inhibitor of intra-lysosomal BCP crystal dissolution, diminished BCP crystal-induced COX-1 mRNA expression. CONCLUSIONS: These findings indicate that BCP crystals can augment PG production in OASF through induction of COX-1 and COX-2. Intra-lysosomal BCP crystal dissolution and activity of the PKC and ERK1/2 signal transduction pathways are required for BCP crystal-induced COX-1 up-regulation. These data add to the evidence suggesting that the constitutive COX-1/inducible COX-2 concept is an over-simplification and suggest that non-selective COX inhibition may be preferable to COX-2 selective inhibition in BCP crystal-associated OA.

The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling.

Eps15 represents the prototype of a family of evolutionarily conserved proteins that are characterized by the presence of the EH domain, a protein-protein interaction module, and that are involved in many aspects of intracellular vesicular sorting. Although biochemical and functional studies have implicated Eps15 in endocytosis, its function in the endocytic machinery remains unclear. Here we show that the Caenorhabditis elegans gene, zk1248.3 (ehs-1), is the orthologue of Eps15 in nematodes, and that its product, EHS-1, localizes to synaptic-rich regions. ehs-1-impaired worms showed temperature-dependent depletion of synaptic vesicles and uncoordinated movement. These phenotypes could be correlated with a presynaptic defect in neurotransmission. Impairment of EHS-1 function in dyn-1(ky51) worms, which express a mutant form of dynamin and display a temperature-sensitive locomotion defect, resulted in a worsening of the dyn-1 phenotype and uncoordination at the permissive temperature. Thus, ehs-1 and dyn-1 interact genetically. Moreover, mammalian Eps15 and dynamin protein were shown to interact in vivo. Taken together, our results indicate that EHS-1 acts in synaptic vesicle recycling and that its function might be linked to that of dynamin.

Emergency department evaluation and treatment of hand injuries.

This article focuses on disorders of the hand most commonly presented to the practitioner in an emergency setting. An initial review of functional anatomy is followed by discussions of the clinical findings and treatment of fractures, tendon injuries, infections, nailbed injuries, high-pressure injection injuries, and nerve injuries. The information presented in this article provides a basis for proper evaluation, diagnosis, and treatment of hand injuries.

Improving medical risk factor reporting on birth certificates in Alabama.

BACKGROUND: In 1995, a program was begun at the University of South Alabama (USA) to improve the reporting of medical risk factors on birth certificates. METHODS: Data on medical risk factors for USA Hospital and the remainder of the state for 1994 and 1996 were examined to observe the effects of the USA Medical Center program. RESULTS: The number of medical risk factors reported changed markedly between 1994 and 1996 for most items and changed hardly at all for the remainder of the state. The changes for selected factors from 1994 to 1996 were as follows: anemia, 19 (0.4% of all birth certificates) to 489 (12.3%); acute or chronic lung disease, 1 (<0.1%) to 405 (10.2%); cardiac disease, 10 (0.2%) to 99 (2.5%); diabetes, 111 (2.6%) to 160 (4.0%); genital herpes, 3 (0.1%) to 81 (2.0%); and hemoglobinopathy, 0 (0%) to 166 (4.2%). Changes in other factors were similar. CONCLUSIONS: The USA Medical Center program has significantly increased the frequency and percent of birth certificates indicating medical risk factors.

Informatic selection of a neural crest-melanocyte cDNA set for microarray analysis.

With cDNA microarrays, it is now possible to compare the expression of many genes simultaneously. To maximize the likelihood of finding genes whose expression is altered under the experimental conditions, it would be advantageous to be able to select clones for tissue-appropriate cDNA sets. We have taken advantage of the extensive sequence information in the dbEST expressed sequence tag (EST) database to identify a neural crest-derived melanocyte cDNA set for microarray analysis. Analysis of characterized genes with dbEST identified one library that contained ESTs representing 21 neural crest-expressed genes (library 198). The distribution of the ESTs corresponding to these genes was biased toward being derived from library 198. This is in contrast to the EST distribution profile for a set of control genes, characterized to be more ubiquitously expressed in multiple tissues (P < 1 x 10(-9)). From library 198, a subset of 852 clustered ESTs were selected that have a library distribution profile similar to that of the 21 neural crest-expressed genes. Microarray analysis demonstrated the majority of the neural crest-selected 852 ESTs (Mel1 array) were differentially expressed in melanoma cell lines compared with a non-neural crest kidney epithelial cell line (P < 1 x 10(-8)). This was not observed with an array of 1,238 ESTs that was selected without library origin bias (P = 0.204). This study presents an approach for selecting tissue-appropriate cDNAs that can be used to examine the expression profiles of developmental processes and diseases.

Nerve growth factor facilitates conditioned taste aversion learning in normal rats.

Chronic intracerebroventricular (i.c.v.) infusion of 3.2 micrograms/day of nerve growth factor (NGF) in normal rats elevated choline acetyltransferase (ChAT) activity of the striatum, medial septum, and basal forebrain and improved performance of a conditioned taste aversion (CTA) task. Relative to bovine serum albumin (BSA) or Cytochrome C treatments, NGF treatment facilitated acquisition and prolonged extinction of a lithium chloride (LiCl)-induced saccharin aversion. This facilitation was evident at saccharin/LiCl intervals ranging up to 1 h. Also, NGF treatment did not increase reactivity to LiCl-induced illness and neither shifted detection thresholds nor altered hedonic reactions to taste stimuli, indicating that NGF did not produce simple changes in sensory function. NGF treatments that elevate ChAT also facilitate memory of CTA in normal, adult rats.