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MicroRNA-9 represses sirtuin 1 (SIRT1) in human keratinocytes

The protein deacetylase sirtuin 1 (SIRT1) is an established regulator of diverse physiological processes and one of several promising targets for pharmacologic modulation of ageing and longevity. In normal human keratinocytes, SIRT1 has been shown to inhibit proliferation and promote differentiation. MicroRNAs (miRNAs), small non-coding RNA molecules that negatively regulate gene expression, have been shown to regulate SIRT1 expression in several cell types. Using western blotting, we show that miR-9 represses SIRT1 expression in the HaCaT human keratinocytes. The attenuation of SIRT1 levels in response to ectopic miR-9 occurred in a dose-dependent manner. As miR-9 expression is known to be under epigenetic control, the effect of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) was examined. Levels of mature miR-9 increased 8-fold following TSA treatment of HaCaT keratinocytes. Expression of the primary transcripts from which miR-9 is derived was also raised in HaCaT keratinocytes exposed to TSA, with a 7-fold elevation of pri-miR-9-1 and 4-fold increase of pri-miR-3. In contrast the DNA methyl transferase inhibitor 5-deoxy-azacytidine (DAC) had little effect on miR-9 or primary miR-9 expression. Together, our findings point to a role for chromatin remodelling in regulating miR-9 levels in human keratinocytes and in turn modulation of SIRT1 expression by miR-9

Macronutrient Balance and Dietary Glycemic Index in Pregnancy Predict Neonatal Body Composition

The influence of maternal macronutrient balance and dietary glycemic index (GI) on neonatal body composition has received little study. We hypothesized that the overall quantity and quality of macronutrients, particularly carbohydrate, in the maternal diet could have trimester-specific effects on neonatal growth and body composition in women at risk of gestational diabetes. Maternal diet was assessed using 3-day food records in mid (n = 96) and late (n = 88) pregnancy as part of the GI Baby 3 study. Neonatal body composition was assessed by air-displacement plethysmography within 48 h of birth, adjusted for length, and expressed as fat mass index (FMI) and fat-free mass index (FFMI). In mid pregnancy, higher maternal intake of carbohydrate energy was negatively correlated with infant FFMI (p = 0.037). In late pregnancy, higher dietary GI was associated with lower FFMI (p = 0.010) and higher carbohydrate energy predicted lower FMI (p = 0.034). Higher fat intake (%E) and saturated fat, but not protein, also predicted neonatal body composition (higher FFMI in mid pregnancy and higher FMI in late pregnancy). Depending on pregnancy stage, a high carbohydrate-low fat diet, particularly from high glycemic sources, may reduce neonatal indices of both lean mass and adiposity

Telemetry tails: a practical method for attaching animal-borne devices to small vertebrates in the field

Context. Continued miniaturisation of tracking technology increases its utility in animal applications. However, species morphology often dictates the type of animal-borne device (ABD) that can be used, and how it is attached. The morphology of species within Peramelemorphia preclude them from the standard collar attachment of ABDs for terrestrial mammals. Aims. This paper describes a method for the tail-mount attachment of ABDs, and deployment results for Peramelemorphia across arid, semi-arid and temperate Australia to (a) test the performance of attachments and ABDs in the field and (b) discuss the animal welfare considerations for this attachment method. Methods. Tail-mount attachment of ABDs were field-tested on a total of 80 greater bilbies (Macrotis lagotis), and 14 long-nosed bandicoots (Perameles nasuta). Key results. Time to natural detachment (TTND) was between 2 and 52 days, with 65.74% (142 of 216) remaining on until manual removal. For ABDs that were manually removed, attachments were retained for up to 94 days. The method used for tail-mount attachment of ABDs to long-nosed bandicoots resulted in significantly shorter TTND compared with the method used for bilbies, and environmental factors (high temperatures and rainfall) had a negative effect on TTND. Tail-mount attached global positioning system (GPS) sensors collected large quantities of accurate data, with a maximum fix success rate of 83.38%. Damage to GPS (antenna breakage and water ingress) during deployment, however, impacted performance. In environments with frequent rainfall and waterlogged soils, the tape on a small proportion (6.25%) of (n = 192)attachments to bilbies caused tail injury. All injuries were resolvable, with most requiringminimal to no veterinary intervention. Key conclusions. Attachment longevity can be affectedby how the ABD is mounted to the tail, the species and the deployment environment. Theenvironment can also affect which adhesive tapes are suitable for ABD attachment. However, thismethod is highly modifiable, practical for field application and can have long retention timesrelative to other temporary methods. Implications. This ABD tail-mount attachment methodadds another tool to the telemetry tool-kit, with all the benefits of a low-tech, low-cost, passivedrop-off type attachment. This method has demonstrated practicality for Peramelemorphia, withpotential application to other suitable small vertebrates

Lower glycemic load meals reduce diurnal glycemic oscillations in women with risk factors for gestational diabetes

Objective Maternal glycemia plays a key role in fetal growth. We hypothesized that lower glycemic load (GL) meals (lower glycemic index, modestly lower carbohydrate) would substantially reduce day-long glucose variability in women at risk of gestational diabetes mellitus (GDM). Research design and methods A crossover study of 17 women (mean±SD age 34.8±4 years; gestational weeks 29.3±1.3; body mass index 23.8±4.7 kg/m2) who consumed a low GL or a high GL diet in random order, 1-day each, over 2 consecutive days. Diets were energy-matched and fiber-matched with 5 meals per 24 hours. All food was provided. Continuous glucose monitoring was used to assess diurnal glycemia. Results Maternal glucose levels were 51% lower on the low GL day with lower incremental area under the curve (iAUC±SEM 549±109 vs 1120±198 mmol/L min, p=0.015). Glycemic variability was significantly lower on the low GL day, as demonstrated by a lower average SD (0.7±0.1 vs 0.9±0.1, p<0.001) and lower mean amplitude of glycemic excursions (2.1±0.2 vs 2.7±0.2 mmol/L, p<0.001). Conclusions A lower GL meal plan in pregnancy acutely halves day-long maternal glucose levels and reduces glucose variability, providing further evidence to support the utility of a low GL diet in pregnancy

Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds

PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL

How South Pacific mangroves may respond to predicted climate change and sea level rise

In the Pacific islands the total mangrove area is about 343,735 ha, with largest areas in Papua New Guinea, Solomon Islands, Fiji and New Caledonia. A total of 34 species of mangroves occur, as well as 3 hybrids. These are of the Indo-Malayan assemblage (with one exception), and decline in diversity from west to east across the Pacific, reaching a limit at American Samoa. Mangrove resources are traditionally exploited in the Pacific islands, for construction and fuel wood, herbal medicines, and the gathering of crabs and fish. There are two main environmental settings for mangroves in the Pacific, deltaic and estuarine mangroves of high islands, and embayment, lagoon and reef flat mangroves of low islands. It is indicated from past analogues that their close relationship with sea-level height renders these mangrove swamps particularly vulnerable to disruption by sea-level rise. Stratigraphic records of Pacific island mangrove ecosystems during sea-level changes of the Holocene Period demonstrate that low islands mangroves can keep up with a sea-level rise of up to 12 cm per 100 years. Mangroves of high islands can keep up with rates of sea-level rates of up to 45 cm per 100 years, according to the supply of fluvial sediment. When the rate of sea-level rise exceeds the rate of accretion, mangroves experience problems of substrate erosion, inundation stress and increased salinity. Rise in temperature and the direct effects of increased CO2 levels are likely to increase mangrove productivity, change phenological patterns (such as the timing of flowering and fruiting), and expand the ranges of mangroves into higher latitudes. Pacific island mangroves are expected to demonstrate a sensitive response to the predicted rise in sea-level. A regional monitoring system is needed to provide data on ecosystem changes in productivity, species composition and sedimentation. This has been the intention of a number of programs, but none has yet been implemented

Informing investment to reduce inequalities: a modelling approach

Background: Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives: To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and methods: Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results: Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions: Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for reducing inequalities were regulatory and tax options. Interventions focused on individual agency were much less likely to impact on inequalities, even when targeted at the most deprived communities

The development of a new measure of quality of life in the management of gastro-oesophageal reflux disease: the Reflux Questionnaire.

INTRODUCTION This paper reports on the development of a new measure of health-related quality of life for use among patients with gastro-oesophageal reflux disease (GORD), funded as part of the REFLUX trial. This is a large UK multi centre trial that aims to compare the clinical and cost effectiveness of minimal access surgery with best medical treatment for patients with GORD within the NHS. Method Potential items were identified via a series of interviews and focus groups carried out with patients who were receiving/had received medical or surgical treatment for GORD. The final measure consisted of 31 items covering 7 categories (Heartburn; Acid reflux; Wind; Eating and swallowing; Bowel movements; Sleep; Work, physical and social activities). The measure produced two outputs: a quality of life score (RQLS) and five Reflux symptom scores. Reliability (internal consistency), criterion validity with the SF-36 and, sensitivity to change in terms of relationship with reported change in prescribed medication were assessed amongst a sample of 794 patients recruited into the trial. RESULTS The measure was shown to be internally consistent, to show criterion validity with the SF-36 and sensitive to changes in patients use of prescribed medication at baseline and 3 month follow-up. DISCUSSION The Reflux questionnaire is a new self-administered questionnaire for use amongst patients with GORD. Initial findings suggest that the new measure is valid, reliable, acceptable to respondents and simple to administer in both a clinical and research context

The influence of föhn winds on annual and seasonal surface melt on the Larsen C Ice Shelf, Antarctica

Abstract. Warm, dry föhn winds are observed over the Larsen C Ice Shelf year-round and are thought to contribute to the continuing weakening and collapse of ice shelves on the eastern Antarctic Peninsula (AP). We use a surface energy balance (SEB) model, driven by observations from two locations on the Larsen C Ice Shelf and one on the remnants of Larsen B, in combination with output from the Antarctic Mesoscale Prediction System (AMPS), to investigate the year-round impact of föhn winds on the SEB and melt from 2009 to 2012. Föhn winds have an impact on the individual components of the surface energy balance in all seasons and lead to an increase in surface melt in spring, summer and autumn up to 100 km away from the foot of the AP. When föhn winds occur in spring they increase surface melt, extend the melt season and increase the number of melt days within a year. Whilst AMPS is able to simulate the percentage of melt days associated with föhn with high skill, it overestimates the total amount of melting during föhn events and non-föhn events. This study extends previous attempts to quantify the impact of föhn on the Larsen C Ice Shelf by including a 4-year study period and a wider area of interest and provides evidence for föhn-related melting on both the Larsen C and Larsen B ice shelves. </jats:p