Resource factors for mental health resilience in early childhood: An analysis with multiple methodologies

Extent: 23p.Background: Given that relatively little is known about the development of resilience in early childhood, this longitudinal study aimed to identify preschool resource factors associated with young children’s mental health resilience to family adversity. Methods: A community sample of 474 young Australian children was assessed in preschool (mean age 4.59 years, 49% male), and again two years later after their transition into formal schooling. At each assessment, standard questionnaires were used to obtain ratings from both parents and teachers about the quality of children’s relationships with parents and teachers, children’s self-concept and self-control, mental health (Strengths and Difficulties Questionnaire), and family adversities (including stressful life events and socioeconomic disadvantage). Results: Greater exposure to cumulative family adversities was associated with both greater teacher- and parent-reported child mental health difficulties two years later. Multiple methodologies for operationalizing resilience were used to identify resources associated with resilient mental health outcomes. Higher quality child–parent and child-teacher relationships, and greater child self-concept and self-control were associated with resilient mental health outcomes. With the exception of child-teacher relationships, these resources were also prospective antecedents of subsequent resilient mental health outcomes in children with no pre-existing mental health difficulties. Child–parent relationships and child self-concept generally had promotive effects, being equally beneficial for children facing both low- and high-adversity. Child self-control demonstrated a small protective effect on teacher-reported outcomes, with greater self-control conferring greater protection to children under conditions of high-adversity. Conclusions: Findings suggest that early intervention and prevention strategies that focus on fostering child-adult relationship quality, self-concept, and self-control in young children may help build children’s mental health and their resilience to family adversities.Lauren R Miller-Lewis, Amelia K Searle, Michael G Sawyer, Peter A Baghurst and Darren Hedle

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort

Supranuclear eye movements and nystagmus in children: A review of the literature and guide to clinical examination, interpretation of findings and age-appropriate norms.

Abnormal eye movements in children present a significant challenge to Ophthalmologists and other healthcare professionals. Similarly, examination of supra-nuclear eye movements in children and interpretation of any resulting clinical signs can seem very complex. A structured assessment is often lacking although in many cases, simple clinical observations, combined with a basic understanding of the underlying neurology, can hold the key to clinical diagnosis. As the range of underlying diagnoses for children with abnormal eye movements is broad, recognising clinical patterns and understanding their neurological basis is also imperative for ongoing management. Here we present a review and best practice guide for a structured, methodical clinical examination of supranuclear eye movements in children, a guide to clinical interpretation and age-appropriate norms. We also detail the more common specific clinical findings and how they should be interpreted and used to guide further management. In summary, this review will encourage clinicians to combine a structured assessment and a logical interpretation of the resulting clinical signs, in order to recognise patterns of presentation and avoid unnecessary investigations and protracted delays in diagnosis and clinical care

Transduction of Brain Dopamine Neurons by Adenoviral Vectors Is Modulated by CAR Expression: Rationale for Tropism Modified Vectors in PD Gene Therapy

Gene-based therapy is a new paradigm for the treatment of Parkinson disease (PD) and offers considerable promise for precise targeting and flexibility to impact multiple pathobiological processes for which small molecule agents are not available. Some success has been achieved utilizing adeno-associated virus for this approach, but it is likely that the characteristics of this vector system will ultimately create barriers to progress in clinical therapy. Adenovirus (Ad) vector overcomes limitations in payload size and targeting. The cellular tropism of Ad serotype 5 (Ad5)-based vectors is regulated by the Ad attachment protein binding to its primary cellular receptor, the coxsackie and adenovirus receptor (CAR). Many clinically relevant tissues are refractory to Ad5 infection due to negligible CAR levels but can be targeted by tropism-modified, CAR-independent forms of Ad. Our objective was to evaluate the role of CAR protein in transduction of dopamine (DA) neurons in vivo.Ad5 was delivered to the substantia nigra (SN) in wild type (wt) and CAR transgenic animals. Cellular tropism was assessed by immunohistochemistry (IHC) in the SN and striatal terminals. CAR expression was assessed by western blot and IHC. We found in wt animals, Ad5 results in robust transgene expression in astrocytes and other non-neuronal cells but poor infection of DA neurons. In contrast, in transgenic animals, Ad5 infects SNc neurons resulting in expression of transduced protein in their striatal terminals. Western blot showed low CAR expression in the ventral midbrain of wt animals compared to transgenic animals. Interestingly, hCAR protein localizes with markers of post-synaptic structures, suggesting synapses are the point of entry into dopaminergic neurons in transgenic animals.These findings demonstrate that CAR deficiency limits infection of wild type DA neurons by Ad5 and provide a rationale for the development of tropism-modified, CAR-independent Ad-vectors for use in gene therapy of human PD

Living on a flammable planet: interdisciplinary, cross-scalar and varied cultural lessons, prospects and challenges: Table 1.

Living with fire is a challenge for human communities because they are influenced by socio-economic, political, ecological and climatic processes at various spatial and temporal scales. Over the course of 2 days, the authors discussed how communities could live with fire challenges at local, national and transnational scales. Exploiting our diverse, international and interdisciplinary expertise, we outline generalizable properties of fire-adaptive communities in varied settings where cultural knowledge of fire is rich and diverse. At the national scale, we discussed policy and management challenges for countries that have diminishing fire knowledge, but for whom global climate change will bring new fire problems. Finally, we assessed major fire challenges that transcend national political boundaries, including the health burden of smoke plumes and the climate consequences of wildfires. It is clear that to best address the broad range of fire problems, a holistic wildfire scholarship must develop common agreement in working terms and build across disciplines. We must also communicate our understanding of fire and its importance to the media, politicians and the general public. This article is part of the themed issue ‘The interaction of fire and mankind’

Flavonoid profiling and transcriptome analysis reveals new gene–metabolite correlations in tubers of Solanum tuberosum L.

Anthocyanin content of potato tubers is a trait that is attracting increasing attention as the potential nutritional benefits of this class of compound become apparent. However, our understanding of potato tuber anthocyanin accumulation is not complete. The aim of this study was to use a potato microarray to investigate gene expression patterns associated with the accumulation of purple tuber anthocyanins. The advanced potato selections, CO97216-3P/PW and CO97227-2P/PW, developed by conventional breeding procedures, produced tubers with incomplete expression of tuber flesh pigmentation. This feature permits sampling pigmented and non-pigmented tissues from the same tubers, in essence, isolating the factors responsible for pigmentation from confounding genetic, environmental, and developmental effects. An examination of the transcriptome, coupled with metabolite data from purple pigmented sectors and from non-pigmented sectors of the same tuber, was undertaken to identify these genes whose expression correlated with elevated or altered polyphenol composition. Combined with a similar study using eight other conventional cultivars and advanced selections with different pigmentation, it was possible to produce a refined list of only 27 genes that were consistently differentially expressed in purple tuber tissues compared with white. Within this list are several new candidate genes that are likely to impact on tuber anthocyanin accumulation, including a gene encoding a novel single domain MYB transcription factor

Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma

Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration. Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy. Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit

Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma

Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations.Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration.Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy.Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit

Television viewing, food preferences, and food habits among children: A prospective epidemiological study

<p>Abstract</p> <p>Background</p> <p>Obesity has increased since the early 1980s, and despite numerous attempts, effective strategies to counter this worldwide epidemic are lacking. Food preferences are established early in life and are difficult to change later. There is therefore a need to identify factors that influence the development of food preferences. Our aim was therefore, to investigate cross-sectional and prospective associations between TV viewing habits and food preferences and habits, respectively. We hypothesized that more TV viewing was associated with less healthy concomitant and future food preferences and food habits.</p> <p>Methods</p> <p>Data are from the Danish part of European Youth Heart Study (EYHS) I and II, a prospective cohort study conducted among 8-10-year-old and 14-16-year-old Danes in 1997-98. Six years later 2003-04 the 8-10-year-olds were followed up at age 14-16 years, and a new group of 8-10-year olds were included. Data were analysed using mixed linear regression analysis. Cross-sectional analyses included 697 8-10-year-olds and 495 14-16-year-olds. Prospective analyses included 232 pupils with complete data at baseline and follow-up. Associations between TV viewing habits and the sum of healthy food preferences (ΣHFP), and the sum of healthy food habits (ΣHFH), respectively, were examined.</p> <p>Results</p> <p>Inverse cross-sectional associations between TV viewing (h/day) and both ΣHFP and ΣHFH were present for both the 8-10-year-old and the 14-16-year-old boys and girls. The frequency of meals in front of the TV (times/week) was also inversely associated with ΣHFP among 8-10-year-old boys, and with ΣHFH in all sex- and age groups. Among girls, baseline TV viewing (h/day) was directly associated with adverse development in the ΣHFP during follow-up. The concomitant 6-year changes in ΣHFH and TV viewing (h/day) were inversely associated in boys.</p> <p>Conclusions</p> <p>Long time spent on TV viewing, and possibly to a lesser degree, frequent consumption of meals during TV viewing, seem to be associated with generally having unhealthy food preferences and food habits among school-aged children. These associations, however, were not generally persistent after 6 years of follow-up.</p