Carious lesions in permanent dentitions are reduced in remote Indigenous Australian children taking part in a non-randomised preventive trial

We tested the effect of an annual caries preventive intervention, delivered by a fly-in/fly-out oral health professional team, with Indigenous children residing in a remote Australian community. Around 600 Indigenous children aged 5 to 17 years were invited to participate at baseline, of who 408 had caregiver consent. One hundred and ninety-six consented to the epidemiological examination and intervention (Intervention group) and 212 consented to the epidemiological examination only (Comparison group). The intervention, which occurred annually, comprised placement of fissure sealants on suitable teeth, and application of povidone-iodine and fluoride varnish to the whole dentition, following completion of any necessary restorative dental treatment. Standard diet and oral hygiene advice were provided. Caries increment (number of tooth surfaces with new dental caries) in both deciduous and permanent dentitions was measured at the 2-year follow-up. Comparison group children had significantly higher number of new surfaces with advanced caries in the permanent dentition than the Intervention group (IRR = 1.61; 95% CI: 1.02-2.54; p = 0.04); with a preventive fraction of 43%. The effect of intervention remained significant with children in the Comparison group developing significantly more advanced caries lesions in the permanent dentition than the Intervention group children in the adjusted multivariable analysis (IRR = 2.21; 95% CI: 1.03-4.71). Indigenous children exposed to the intervention had less increment in advanced dental caries in the permanent dentition than those not exposed to the intervention.Ratilal Lalloo, Santosh K. Tadakamadla, Jeroen Kroon, Lisa M. Jamieson, Robert S. Ware, Newell W. Johnso

Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea

Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Understanding the genetics of adult-onset dilated cardiomyopathy: what a clinician needs to know

There is increasing understanding of the genetic basis to dilated cardiomyopathy and in this review, we offer a practical primer for the practising clinician. We aim to help all clinicians involved in the care of patients with dilated cardiomyopathy to understand the clinical relevance of the genetic basis of dilated cardiomyopathy, introduce key genetic concepts, explain which patients and families may benefit from genetic testing, which genetic tests are commonly performed, how to interpret genetic results, and the clinical applications of results. We conclude by reviewing areas for future research in this dynamic field.[GRAPHICS]

Truncating Variants in Titin Independently Predict Early Arrhythmias in Patients With Dilated Cardiomyopathy

10.1016/j.jacc.2017.03.530Journal of the American College of Cardiology69192466-246

An evaluation of an Eye Tracker as a Device for Computer Input

Since humans direct their visual attention by means of eye movements, a device which monitors eye movements should be a natural “pick” device for selecting objects visually present on a monitor. The results from an experimental investigation of an eye tracker as a computer input device are presented. Three different methods were used to select the object looked at; these were a button press, prolonged fixation or “dwell” and an on screen select button. The results show that an eye tracker can be used as a fast selection device providing that the target size is not too small. If the targets are small speed declines and errors increase rapidly