ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism.

Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and are among the most common neurogenetic disorders. Identifying the causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once the defect is known, researchers face the challenge of deciphering the underlying disease mechanism. Here we characterize large biallelic deletions in the region encoding the ATAD3C, ATAD3B and ATAD3A genes.

Prevalence and determinants of cessation of exclusive breastfeeding in the early postnatal period in Sydney, Australia.

Background: Optimal breastfeeding has benefits for the mother-infant dyads. This study investigated the prevalence and determinants of cessation of exclusive breastfeeding (EBF) in the early postnatal period in a culturally and linguistically diverse population in Sydney, New South Wales, Australia.

Methods: The study used routinely collected perinatal data on all live births in 2014 ( = 17,564) in public health facilities in two Local Health Districts in Sydney, Australia.

In silico analysis of five missense mutations in CYP1B1 gene in Pakistani families affected with primary congenital glaucoma.

Purpose: The purpose of this study was to characterize the five missense mutations in CYP1B1 gene identified in Pakistani families affected with primary congenital glaucoma (PCG) using various bioinformatics and protein modeling tools.

Methods: We previously reported four novel missense mutations in CYP1B1 gene segregating in consanguineous Pakistani families. These mutations were identified by direct sequencing of all coding exons, the exon-intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA from affected and unaffected family members.

Addiction stigma and the biopolitics of liberal modernity: A qualitative analysis.

Definitions of addiction have never been more hotly contested. The advance of neuroscientific accounts has not only placed into public awareness a highly controversial explanatory approach, it has also shed new light on the absence of agreement among the many experts who contest it. Proponents argue that calling addiction a 'brain disease' is important because it is destigmatising.

The impact of parental offending on offspring aggression in early childhood: a population-based record linkage study.

Purpose: To examine the impact of parental criminal offending, both paternal and maternal, on offspring aggression at age 5 years, while also considering key risk factors, including parental mental illness, child's sex, and socioeconomic disadvantage.

Methods: The sample comprised 69,116 children, with linked parental information, from the New South Wales Child Development Study, a population-based multi-agency, multi-generational record linkage study that combines information from a teacher-reported cross-sectional survey of early childhood development at age 5 years (the 2009 Australian Early Development Census; AEDC) with data obtained via administrative records from multiple sources (e.g.

Infant feeding practices and diarrhoea in sub-Saharan African countries with high diarrhoea mortality.

Background: The impacts of optimal infant feeding practices on diarrhoea have been documented in some developing countries, but not in countries with high diarrhoea mortality as reported by the World Health Organisation/United Nations Children's Fund. We aimed to investigate the association between infant feeding practices and diarrhoea in sub-Saharan African countries with high diarrhoea mortality.

Method: The study used the most recent Demographic and Health Survey datasets collected in nine sub-Saharan African countries with high diarrhoea mortality, namely: Burkina Faso (2010, N = 9,733); Demographic Republic of Congo (2013; N = 10,458); Ethiopia (2013, N = 7,251); Kenya (2014, N = 14,034); Mali (2013, N = 6,365); Niger (2013, N = 7,235); Nigeria (2013, N = 18,539); Tanzania (2010, N = 5,013); and Uganda (2010, N = 4,472).

The Impact of Antenatal Depression on Perinatal Outcomes in Australian Women.

Background: In Australia, there is limited evidence on the impact of antenatal depression on perinatal outcomes. This study investigates the association between maternal depressive symptoms during pregnancy and key perinatal outcomes, including birth weight, gestational age at birth, breastfeeding indicators and postnatal depressive symptoms.

Method: A retrospective cohort of mothers (N = 17,564) of all infants born in public health facilities within South Western Sydney Local Health District and Sydney Local Health District in 2014, in the state of New South Wales (NSW), Australia, was enumerated from routinely collected antenatal data to investigate the risk of adverse perinatal outcomes associated with maternal depressive symptoms during pregnancy.

Subcutaneous Lidocaine Infusion for Pain in Patients with Cancer.

Background: Intravenous lidocaine is effective in treating pain. Limited studies have assessed the effectiveness and safety of subcutaneous lidocaine infusions.

Methods: We conducted a retrospective review of patients with cancer who received subcutaneous lidocaine infusions for pain.

Knowledge, attitudes and practices of Australian medical students towards influenza vaccination.

Background: Annual influenza vaccination is recommended but not compulsory for healthcare workers in Australia, including medical students. A quarter of healthcare workers are estimated to have an influenza infection in any given year, with a subsequent transmission risk to colleagues and patients. During clinical placements, medical students are also at risk of influenza.

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles.

The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought.

Pre-existing risk factors for in-hospital death among older patients could be used to initiate end-of-life discussions rather than Rapid Response System calls: A case-control study.

Aim: To investigate associations between clinical parameters - beyond the evident physiological deterioration and limitations of medical treatment - with in-hospital death for patients receiving Rapid Response System (RRS) attendances.

Methods: Retrospective case-control analysis of clinical parameters for 328 patients aged 60 years and above at their last RRS call during admission to a single teaching hospital in the 2012-2013 calendar years. Generalised estimating equation modelling was used to compare the deceased with a randomly selected sample of those who had RRS calls and survived admission (controls), matched by age group, sex, and hospital ward.

Closing the Aboriginal child injury gap: targets for injury prevention.

Objective: To describe the leading mechanisms of hospitalised unintentional injury in Australian Aboriginal children and identify the injury mechanisms with the largest inequalities between Aboriginal and non-Aboriginal children.

Methods: We used linked hospital and mortality data to construct a whole of population birth cohort including 1,124,717 children (1,088,645 non-Aboriginal and 35,749 Aboriginal) born in the state of New South Wales (NSW), Australia, between 1 July 2000 and 31 December 2012. Injury hospitalisation rates were calculated per person years at risk for injury mechanisms coded according to the ICD10-AM classification.

Mixed gonococcal infections in a high-risk population, Sydney, Australia 2015: implications for antimicrobial resistance surveillance?

Objectives: Previous studies have shown that mixed-strain gonococcal infections can occur. However, it remains unclear whether such infections impact upon the reliability of Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance. In this study, we aimed to resolve this question by intensively sampling isolates from gonorrhoea-positive specimens in a high-risk population in Sydney, Australia.

Examining Intervention Design: Lessons from the Development of Eight Related Malaria Health Care Intervention Studies.

-Rigorous evidence of "what works" to improve health care is in demand, but methods for the development of interventions have not been scrutinized in the same ways as methods for evaluation. This article presents and examines intervention development processes of eight malaria health care interventions in East and West Africa. A case study approach was used to draw out experiences and insights from multidisciplinary teams who undertook to design and evaluate these studies.

Computational Model of the Arterial and Venous Needle During Hemodialysis.

Arteriovenous fistulae (AVF) are the favored choice of vascular access but still have poor long-term success. Hemodynamic parameters play an important role in vascular health and have been linked to the development of intimal hyperplasia (IH), a pathological growth of the blood vessel initiated by injury. This study aimed to investigate the hemodynamics surrounding the arterial needle (AN) and venous needle (VN), using computational fluid dynamics.

Mangrove response to environmental change in Australia's Gulf of Carpentaria.

Across their range, mangroves are responding to coastal environmental change. However, separating the influence of human activities from natural events and processes (including that associated with climatic fluctuation) is often difficult. In the Gulf of Carpentaria, northern Australia (Leichhardt, Nicholson, Mornington Inlet, and Flinders River catchments), changes in mangroves are assumed to be the result of natural drivers as human impacts are minimal.

Phenotype of sarcopenic obesity in older individuals with a history of falling.

Background: Although sarcopenic obesity is associated with disability in middle-aged community-dwelling individuals, the phenotype of sarcopenic obesity in people 65 and older, especially those with a history of falls, remain unknown. To fill this knowledge gap, the goal of this study was to obtain a comprehensive phenotype of sarcopenic obesity in this high-risk population.

Methods: Cross-sectional study of 680 subjects (mean age=79±9, 65% female) assessed between 2009 and 2013 at the Falls and Fractures Clinic, Nepean Hospital (Penrith, Australia).

CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular and pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of which TDP-43 is a major component, are a characteristic pathological feature of most ALS and FTD patients. Here we use genome-wide linkage analysis in a large ALS/FTD kindred to identify a novel disease locus on chromosome 16p13.

Binding of transcription factor GabR to DNA requires recognition of DNA shape at a location distinct from its cognate binding site.

Mechanisms for transcription factor recognition of specific DNA base sequences are well characterized and recent studies demonstrate that the shape of these cognate binding sites is also important. Here, we uncover a new mechanism where the transcription factor GabR simultaneously recognizes two cognate binding sites and the shape of a 29 bp DNA sequence that bridges these sites. Small-angle X-ray scattering and multi-angle laser light scattering are consistent with a model where the DNA undergoes a conformational change to bend around GabR during binding.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

Impaired 2-AG Signaling in Hippocampal Glutamatergic Neurons: Aggravation of Anxiety-Like Behavior and Unaltered Seizure Susceptibility.

Background: Postsynaptically generated 2-arachidonoylglycerol activates the presynaptic cannabinoid type-1 receptor, which is involved in synaptic plasticity at both glutamatergic and GABAergic synapses. However, the differential function of 2-arachidonoylglycerol signaling at glutamatergic vs GABAergic synapses in the context of animal behavior has not been investigated yet.

Methods: Here, we analyzed the role of 2-arachidonoylglycerol signaling selectively in hippocampal glutamatergic neurons.

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues.

Reasons underlying behaviour of motorcyclists disregarding traffic regulations in urban areas of Indonesia.

Over the last decade, motorcycle use has been rapidly increasing in Indonesia as have violations of traffic rules committed by motorcyclists. This study aims to explore the impacts of motorcyclists' attitudes, habits, preferences, and travel patterns on their behaviour in disregarding traffic regulations in three cities in Indonesia. The theory of planned behaviour and structural equation modelling are employed to explore these relationships.