Inhibition of the glycaemic response by onion : a comparison between lactose-tolerant and lactose-intolerant adults

This document is the Accepted Manuscript of the following article: R Hoffman, G Ranjbar and A M Madden, ‘Inhibition of the glycaemic response by onion: a comparison between lactose-tolerant and lactose-intolerant adults’, European Journal of Clinical Nutritin, (2016), 70: 1089-1091. The Version of Record is available online at doi: 10.1038/ejcn.2016.44.This pilot study compared inhibition of the glycaemic response to glucose by a dietary source of quercetin glucosides (onion) in lactose-tolerant adults (n = 12) and lactose-intolerant adults (n = 12). We hypothesised that lactose-intolerant people (who do not express lactase) will retain intact quercetin glucosides that can inhibit glucose uptake via the glucose transporter SGLT1 whereas lactose-tolerant people (who do express lactase) will hydrolyse quercetin glucosides to free quercetin which does not inhibit glucose uptake. In a glucose tolerance test, reduction of peak glucose levels by an onion meal was higher in lactose-intolerant people than lactose-tolerant people (44.2% versus 19.3%, p = 0.04). Incremental area under the blood glucose curve was reduced more in lactose-intolerant people, but was not statistically significantly (54.5% versus 42.1%, p = 0.42). A diet containing quercetin glucosides may be of greater benefit for glycaemic control in lactose-intolerant people than in lactose-tolerant people.Peer reviewedFinal Accepted Versio

Effectiveness of early intervention programs for parents of preterm infants: a meta-review of systematic reviews

Background: Various intervention programs exist for parents of preterm babies and some systematic reviews (SRs) have synthesised the evidence of their effectiveness. These reviews are, however, limited to specific interventions, components, or outcomes, and a comprehensive evidence base is lacking. The aim of this meta-review was to appraise and meta-synthesise the evidence from existing SRs to provide a comprehensive evidence base on the effectiveness of interventions for parents of preterm infants on parental and infant outcomes. Methods: We conducted a comprehensive search of the following databases to identify relevant SRs: Cochrane library, Web of science, EMBASE, CINAHL, British Nursing Index, PsycINFO, Medline, ScienceDirect, Scopus, IBSS, DOAJ, ERIC, EPPI-Centre, PROSPERO, WHO Library. Additional searches were conducted using authors’ institutional libraries, Google Scholar, and the reference lists of identified reviews. Identified articles were screened in two stages against an inclusion criteria with titles and abstracts screened first followed by full-text screening. Selected SRs were appraised using the AMSTAR tool. Extracted data using a predesigned tool were synthesised narratively examining the direction of impact on outcomes. Results: We found 11 SRs eligible for inclusion that synthesised a total of 343 quantitative primary studies. The average quality of the SRs was ‘medium’. Thirty four interventions were reported across the SRs with considerable heterogeneity in the structural framework and the targeted outcomes that included maternal-infant dyadic, maternal/parental, and infant outcomes. Among all interventions, Kangaroo Care (KC) showed the most frequent positive impact across outcomes (n = 19) followed by Mother Infant Transaction Program (MITP) (n = 14). Other interventions with most consistent positive impact on infant outcomes were Modified-Mother Infant Transaction Program (M-MITP) (n = 6), Infant Health and Development Program (IHDP) (n = 5) and Creating Opportunities for Parent Empowerment (COPE) (n = 5). Overall, interventions with both home and facility based components showed the most frequent positive impact across outcomes. Conclusions: Neonatal care policy and planning for preterm babies should consider the implementation of interventions with most positive impact on outcomes. The heterogeneity in interventions and outcomes calls for the development and implementation of an integrated program for parents of preterm infants with a clearly defined global set of parental and infant outcomes

Protocol of trans-Tasman feasibility randomised controlled trial of the Younger Women's Wellness After Breast Cancer (YWWACP) lifestyle intervention.

BACKGROUND: Younger women (defined as those < 50 years who are likely pre-menopausal at time of diagnosis) with breast cancer often experience persistent treatment-related side effects that adversely affect their physical and psychological wellbeing. The Women's Wellness After Cancer Program (WWACP) was adapted and piloted in Australia to address these outcomes in younger women. The aims of this feasibility study are to determine (1) the potential to translate the Younger WWACP (YWWACP) intervention to a broader population base in Aotearoa/New Zealand and Australia, and (2) the potential for success of a larger, international, phase ΙΙΙ, randomised controlled trial. METHODS: This bi-national, randomised, single-blinded controlled trial involves two main study sites in Aotearoa/New Zealand (Kōwhai study) and Australia (EMERALD study). Young women aged 18 to 50 years who completed intensive treatment (surgery, chemotherapy, and/or radiotherapy) for breast cancer in the previous 24 months are eligible. The potential to translate the YWWACP to women in these two populations will be assessed according to several feasibility outcomes. These include examining intervention accessibility, acceptability and uptake; intervention sustainability and adherence; the prevalence components of the intervention in the control group; intervention efficacy; participants' perception of measurement burden; the effectiveness of planned recruitment strategies; and trial methods and procedures. The studies collectively aim to enrol 60 participants in the intervention group and 60 participants in the control group (total = 120 participants). DISCUSSION: Ethical approval has been received from the Southern Health and Disability Ethics Committee (Kōwhai ref: 19/STH/215), and UnitingCare Human Research Ethics Committee (EMERALD ref: 202103). This study will provide important data on the feasibility of the refined YWWACP in the trans-Tasman context. This study will account for and harmonise cross-country differences to ensure the success of a proposed international grant application for a phase ΙΙΙ randomised controlled trial of this program to improve outcomes in younger women living with breast cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): Kōwhai ACTRN12620000260921 , registered on 27 February 2020. EMERALD ACTRN12621000447853 , registered on 19 April 2021

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification

Decadal-timescale estuarine geomorphic change under future scenarios of climate and sediment supply

© The Authors, 2009. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Estuaries and Coasts 33 (2010): 15-29, doi:10.1007/s12237-009-9244-y.Future estuarine geomorphic change, in response to climate change, sea-level rise, and watershed sediment supply, may govern ecological function, navigation, and water quality. We estimated geomorphic changes in Suisun Bay, CA, under four scenarios using a tidal-timescale hydrodynamic/sediment transport model. Computational expense and data needs were reduced using the morphological hydrograph concept and the morphological acceleration factor. The four scenarios included (1) present-day conditions; (2) sea-level rise and freshwater flow changes of 2030; (3) sea-level rise and decreased watershed sediment supply of 2030; and (4) sea-level rise, freshwater flow changes, and decreased watershed sediment supply of 2030. Sea-level rise increased water levels thereby reducing wave-induced bottom shear stress and sediment redistribution during the wind-wave season. Decreased watershed sediment supply reduced net deposition within the estuary, while minor changes in freshwater flow timing and magnitude induced the smallest overall effect. In all future scenarios, net deposition in the entire estuary and in the shallowest areas did not keep pace with sea-level rise, suggesting that intertidal and wetland areas may struggle to maintain elevation. Tidal-timescale simulations using future conditions were also used to infer changes in optical depth: though sea-level rise acts to decrease mean light irradiance, decreased suspended-sediment concentrations increase irradiance, yielding small changes in optical depth. The modeling results also assisted with the development of a dimensionless estuarine geomorphic number representing the ratio of potential sediment import forces to sediment export forces; we found the number to be linearly related to relative geomorphic change in Suisun Bay. The methods implemented here are widely applicable to evaluating future scenarios of estuarine change over decadal timescales.This study was supported by the US Geological Survey’s Priority Ecosystems Science program, CALFED Bay/ Delta Program, and the University of California Center for Water Resources

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Effects of self-management, education and specific exercises, delivered by health professionals, in patients with osteoarthritis of the knee

<p>Abstract</p> <p>Background</p> <p>An education self-management program for people with osteoarthritis (OA) of the knee was designed to be delivered by health professionals, incorporating their knowledge and expertise. Improvement in quality of life, health status and pain in response to this program has previously been demonstrated in an uncontrolled pilot study. To more rigorously test the effectiveness of the program we will undertake a randomised controlled trial of people with OA of the knee offering specific self-administered exercises and education, in accordance with the principles of self-management.</p> <p>Aim: To determine whether an education self management program for subjects with Osteoarthritis (OA) of the knee (OAK program) implemented by health professionals in a primary health care setting can achieve and maintain clinically meaningful improvements compared standard medical management in a control group.</p> <p>Methods</p> <p>The effects of standard medical management will be compared with the effects of the OAK program in a single-blind randomized study.</p> <p><it>Participants: </it>146 male and female participants with established OA knee will be recruited. Volunteers with coexistent inflammatory joint disease or serious co-morbidities will be excluded.</p> <p><it>Interventions: </it>Participants will be randomized into either intervention or control groups (delayed start). The intervention group will complete the OA knee program and both groups will be followed for 6 months.</p> <p><it>Measurements: </it>Assessments will be at baseline, 8 weeks and 6 months. SF-36, WOMAC and VAS pain questionnaires will be completed. Isometric quadriceps and hamstring strength will be measured using a dynamometer; knee range of movement using a goniometer; and physical function will be determined by a modified timed up and go test. Data will be analysed using repeated measures ANOVA.</p> <p>Discussion</p> <p>While there is evidence to support the effectiveness of SM programs for people with hypertension, diabetes and asthma, the evidence available for treatment of arthritis remains equivocal. The aim of this study is to determine the effectiveness of a disease specific self-management program for people with OA knee.</p> <p>The study design includes all the important features of a clinical experimental study to minimize bias so the results of the study will provide a high level of evidence. People with OA of the knee have identified pain and problems with daily activities as the most important problems associated with their condition. The outcome measures selected specifically address these issues and have demonstrated validity and are responsive within the range of change expected in response to the intervention. Hence the results of the study will reflect their priorities.</p> <p>The results of the study will provide evidence to guide clinicians and funding bodies seeking to establish priorities regarding the provision of this disease specific program.</p> <p>Trial registration</p> <p>ACTR number: 12607000080426</p