Craniofacial structures and dental development in three patients with Nager syndrome

In Finland, 3 patients have been diagnosed with Nager syndrome (NS) during the last 17 years. Thus the incidence for NS in Finland is 3:1,000,000. The craniofacial structures and dental development of these patients were studied clinically and radiographically at the age of 3-4 years, and compared to age-matched controls and to the norms of the Finnish population. The striking structural finding was a severely short, retrognathic and posteriorly rotated mandible. Especially the ramus was deficient; its height was, on average, less than one-third of that of the control group. All children were tracheostomized neonatally. At the age of 3-4, the lower pharyngeal airway was still severely obstructed or completely closed. Nasopharyngeal airway was wide and the soft palate was missing in all patients. All patients had a complete deciduous dentition, but agenesis of permanent teeth (ranging from 2-10 missing teeth) was observed in each patient. Accelerated dental development was found in two subjects. Condylar ankylosis or severely limited mouth opening were observed.The present findings give new information and quantify earlier observations of craniofacial structures and dental development in NS. Analysis of facial structures suggests that if surgical intervention is needed to enable better breathing, the goal of the structural correction should be aimed at the most deficient structure, namely the ramus height. As a result of severe dentofacial deviation, a treatment process through the growth requires multidisciplinary teamwork of surgeons, pediatrists, orthodontists and prosthodontists.     

Common protective and diverse smooth muscle cell effects of AAV-mediated angiopoietin-1 and -2 expression in rat cardiac allograft vasculopathy

Angiopoietin-1 (Ang1) and Ang2 regulate the maintenance of normal vasculature by direct endothelial and indirect smooth muscle cell (SMC) effects. Dysfunction of vascular wall cells is considered central in cardiac allograft vasculopathy (CAV), where inflammation and arterial injury initiate subsequent intimal SMC proliferation. In this study, we investigated the effect of exogenous Ang1 and Ang2 in chronically rejecting rat cardiac allografts by intracoronary adeno-associated virus (AAV)-mediated gene transfer. Bioluminescent imaging of AAV-transfected syngeneic grafts revealed gradual and stable transgene expression in graft cardiomyocytes. In cardiac allografts, both AAV-Ang1 and AAV-Ang2 decreased inflammation and increased antiapoptotic Bcl-2 mRNA and Bcl-2/Bax ratio at 8 weeks. Only AAV-Ang2 decreased the development of CAV, whereas AAV-Ang1 activated arterial SMC and increased PDGF-A mRNA in the allograft. Collectively, our results show that exogenous Ang1 and Ang2 have similar antiinflammatory and antiapoptotic effects in cardiac allografts. Prolonged AAV-mediated Ang1 transgene expression also induced SMC activation, whereas AAV-Ang2 lacked the SMC activating effects and decreased CAV. Our results thus highlight the common protective and diverse SMC effects of Ang1 and Ang2 in cardiac allograft microenvironment and the importance of timing of angiopoietins to achieve therapeutic effects.     

Validating the Children’s Medicines Use Questionnaire (CMUQ) in Australia

Objective: To pilot test the validity and reliability of the English version of the Children’s Medicines Questionnaire (CMUQ) and to explore the attitudes of Australian caregivers towards the use of medicines in children. Setting: Survey of Australian parents and primary care givers of children 0–15 years. Methods: The questionnaire was translated from Finnish to English then back-translated to ensure semantic equivalence. A total of 153 parents/main caregiver of a child aged 0–15 years were recruited via convenience sampling. Construct validity of the attitudinal section of the CMUQ was performed using exploratory factor analysis. Reliability was assessed using the Cronbach’s alpha coefficient as a marker of internal consistency. Three focus groups were conducted to explore participants’ attitudes towards medicating children and to triangulate quantitative data. Main outcome measure: Construct validity and internal reliability of the CMUQ. Results: Factor analysis generated a parsimonious four factor solution explaining 50% of variance in the data. The four subscales representing the four factor solution each returned a Cronbach’s Alpha coefficient >0.6, indicating good internal consistency. Participants in focus groups were satisfied with the structure and content of the questionnaire. There were 5 emergent themes through focus group discussions with parents and primary care givers of children, regarding the perception of medicines use in children. These included, ‘concerns about the negative effects of medicines’, ‘medicines are useful, necessary and safe in treating illnesses in children’, ‘the body’s natural processes are sufficient in fighting illness’, ‘over the counter medicines are effective and useful in treating illness’, ‘perception of alternative medicines use in children’. Conclusions: The CMUQ is a valid and reliable tool to measure parents’ medicine use for their children in an Australian sample. Although small modifications should be made, this instrument will be valuable in informing the development of medicines information for this cohort in the future.     

Psychoneurotic symptoms and alexithymia in coeliac disease

Objective. Depression, psychological problems and the impairment of quality of life are reported to occur in untreated coeliac disease. Alexithymia (“no words for feelings”) is associated with various gastrointestinal disorders. The aim of this study was to evaluate whether patients with coeliac disease suffer from psychoneurotic symptoms or alexithymia, and whether a gluten-free diet has an impact on the symptoms. Material and methods. The Crown-Crisp Experiential Index (CCEI) and its six subscales were applied to measure neurotic psychopathology, and the 20-item version of the Toronto Alexithymia Scale (TAS-20) and its 3-factor scales to measure alexithymia. The testing was carried out in 20 consecutive adult patients with biopsy-proven coeliac disease before and after one year of treatment on a gluten-free diet. The data were compared with those obtained earlier in non-coeliac Finnish subjects. Results. Somatic anxiety was higher in coeliac disease patients before the introduction of the gluten-free diet than after adhering to the diet. Otherwise, the diet had no significant impact on the CCEI scores. The patients were not suffering from alexithymia, but the TAS-20 score improved significantly during the follow-up. The scores did not differ from those published in the Finnish population. Conclusions. Psychological problems were not common in adult coeliac disease patients. Gluten-free diet had only a minor influence on the symptoms. Common knowledge about coeliac disease and the readily available gluten-free products may have had an impact on these results.     

Transforming growth factor-beta activation in the lung: focus on fibrosis and reactive oxygen species

Transforming growth factor-betas (TGF-beta) regulate a wide variety of cellular functions in normal development and are involved in both tissue homeostasis and disease pathogenesis. The regulation of the TGF-beta family of growth factors is unique because they are targeted to the extracellular matrix in a biologically inactive form. The release from pericellular matrices and the activation of TGF-beta are important mechanisms in several pathophysiologic conditions. Reactive oxygen species (ROS) can activate TGF-beta either directly or indirectly via the activation of proteases. In addition, TGF-beta itself induces ROS production as part of its signal-transduction pathway. The lung is a unique organ, because its structures act as boundaries between gaseous and aqueous phases, allowing the utilization of inhaled oxygen. However, this renders pulmonary tissues vulnerable to the toxic effects of inhaled air. The oxidant pathways are especially relevant in the lung, where TGF-beta is known to have a role in tissue repair and connective tissue turnover. In pulmonary fibrosis, TGF-beta activation is considered as a hallmark of disease progression. More recently, the oxidative effects of cigarette smoking have been found to activate TGF-beta in chronic obstructive pulmonary disease (COPD), a disease consisting of emphysema, airway fibrosis, and focal lung fibrosis.     

Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions

Breast cancer is the most common cancer in women in developed countries and has a well-established genetic component. Germline mutations in a network of genes encoding BRCA1, BRCA2, and their interacting partners confer hereditary susceptibility to breast cancer. Abraxas directly interacts with the BRCA1 BRCT (BRCA1 carboxyl-terminal) repeats and contributes to BRCA1-dependent DNA damage responses, making Abraxas a candidate for yet unexplained disease susceptibility. Here, we have screened 125 Northern Finnish breast cancer families for coding region and splice-site Abraxas mutations and genotyped three tagging single-nucleotide polymorphisms within the gene from 991 unselected breast cancer cases and 868 female controls for common cancer-associated variants. A novel heterozygous alteration, c.1082G>A (Arg361Gln), that results in abrogated nuclear localization and DNA response activities was identified in three breast cancer families and in one additional familial case from an unselected breast cancer cohort, but not in healthy controls (P = 0.002). On the basis of its exclusive occurrence in familial cancers, disease cosegregation, evolutionary conservation, and disruption of critical BRCA1 functions, the recurrent Abraxas c.1082G>A mutation connects to cancer predisposition. These findings contribute to the concept of a BRCA-centered tumor suppressor network and provide the identity of Abraxas as a new breast cancer susceptibility gene.     

Singaporean nurses' provision of guidance to parents on non-pharmacological postoperative pain-relief methods: An educational intervention study

This study examined the impact of an educational intervention (booklet distribution and lectures) on Singaporean nurses' provision of guidance to parents on the use of non-pharmacological methods of pain relief for their child's postoperative pain. Using a quasi-experimental one-group pre- and post-test study design, 134 and 112 registered nurses completed the questionnaires pre- and post-test, respectively. More than 75% of the nurses "always" guided parents to use breathing techniques, relaxation, positioning, comforting/reassurance, helping with activities of daily living, and creating a comfortable environment in the pretest and touch, presence, and distraction in addition to the aforementioned methods in the post-test. The nurses' provision of guidance to parents on all non-pharmacological methods increased, but statistically significant increases only were found in relation to massage and positive reinforcement. The results suggested that the educational intervention had some impact on nurses' provision of guidance to parents on the use of non-pharmacological methods of pain relief for children's postoperative pain. Continuing education in pain management should be provided to nurses in order to equip them with the knowledge to improve their practice.