Changes in BMI and waist circumference in Scottish adults: use of repeated cross-sectional surveys to explore multiple age groups and birth-cohorts

Objective: To document changes in body mass index (BMI) and waist circumference (WC) over a 10-year period 1998-2008, in representative surveys of adults.<p></p> Subjects: Adults aged 18-72 in the Scottish Health Surveys conducted in 1998, 2003 and 2008 were divided, separately for men and women, into eleven 5-year age bands. ‘Synthetic birth-cohorts’ were created by dividing participants into thirteen 5-years-of-birth bands (n=20,423). Weight, height and waist circumference were objectively measured by trained observers.<p></p> Results: Subjects with data available on BMI/waist circumference were 7743/6894 in 1998, 5838/4437 in 2003 and 4688/925 in 2008 with approximately equal gender distributions. Mean BMI and waist were both greater in successive surveys in both men and women. At most specific ages, people were consistently heavier in 2008 than in 1998 by about 1-1.5 BMI units, and waist circumferences were greater, by about 2-6 cm in men and 5-7 cm in women. Greater increases were seen at younger ages between 1998 and 2003 than between 2003 and 2008, however increases continued at older ages, particularly in waist. All birth-cohorts observed over the 10 years 1998-2008 showed increases in both BMI and waist, most marked in the younger groups. The 10-year increases in waist within birth-cohorts (mean 7.4 cm (8.1%) in men and 8.6 cm (10.9%) in women) were more striking than BMI (mean 1.8 kg/m2 (6.6%) in men and 1.5 kg/m2 (6.4%) in women) were particularly steep in older women.<p></p> Conclusion: People were heavier and fatter in 2003 than those of the same age in 1998, with less marked increases in WC between 2003 and 2008 than 1998 and 2003. There were proportionally greater increases in waist circumference than BMI, especially in older women. This suggests a disproportionate increase in body fat, compared to muscle, particularly among older women.<p></p&gt

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Ultrasound assisted casting of an AM60 based metal matrix nanocomposite, its properties, and recyclability

An AM60 magnesium alloy nanocomposite reinforced with 1 wt % of AlN nanoparticles was prepared using an ultrasound (US) assisted permanent-mould indirect-chill casting process. Ultrasonically generated cavitation and acoustic streaming promoted de-agglomeration of particle clusters and distributed the particles throughout the melt. Significant grain refinement due to nucleation on the AlN nanoparticles was accompanied by an exceptional improvement in properties: yield strength increased by 103%, ultimate tensile strength by 115%, and ductility by 140%. Although good grain refinement was observed, the large nucleation undercooling of 14 K limits further refinement because nucleation is prevented by the formation of a nucleation-free zone around each grain. To assess the industrial applicability and recyclability of the nanocomposite material in various casting processes, tests were performed to determine the effect of remelting on the microstructure. With each remelting, a small percentage of effective AlN nanoparticles was lost, and some grain growth was observed. However, even after the third remelting, excellent strength and ductility was retained. According to strengthening models, enhanced yield strength is mainly attributed to Hall-Petch strengthening caused by the refined grain size. A small additional contribution to strengthening is attributed to Orowan strengthening

Liver biopsy-based validation, confirmation and comparison of the diagnostic performance of established and novel non-invasive non-alcoholic fatty liver disease indexes:Results from a large multi-center study

Background: Non-invasive tools (NIT) for non-alcoholic fatty liver disease (NAFLD) screening or diagnosis need to be thoroughly validated using liver biopsies.Purpose: To externally validate NITs designed to differentiate the presence or absence of liver steatosis as well as more advanced disease stages, to confirm fully validated indexes (n = 7 NITs), to fully validate partially validated indexes (n = 5 NITs), and to validate for the first time one new index (n = 1 NIT).Methods: This is a multi-center study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven NAFLD (n = 374, including 237 patients with non-alcoholic steatohepatitis (NASH)) and Controls (n = 81) were recruited. A complete validation analysis was performed to differentiate the presence of NAFLD vs. Controls, NASH vs. NAFL, histological features of NASH, and fibrosis stages.Results: The index of NASH (ION) demonstrated the highest differentiation ability for the presence of NAFLD vs. Controls, with the area under the curve (AUC) being 0.894. For specific histological characterization of NASH, no NIT demonstrated adequate performance, while in the case of specific features of NASH, such as hepatocellular ballooning and lobular inflammation, ION demonstrated the best performance with AUC being close to or above 0.850. For fibrosis (F) classification, the highest AUC was reached by the aspartate aminotransferase to platelet ratio index (APRI) being ~0.850 yet only with the potential to differentiate the severe fibrosis stages (F3, F4) vs. mild or moderate fibrosis (F0–2) with an AUC > 0.900 in patients without T2DM. When we excluded patients with morbid obesity, the differentiation ability of APRI was improved, reaching AUC = 0.802 for differentiating the presence of fibrosis F2–4 vs. F0–1. The recommended by current guidelines index FIB-4 seemed to differentiate adequately between severe (i.e., F3–4) and mild or moderate fibrosis (F0–2) with an AUC = 0.820, yet this was not the case when FIB-4 was used to classify patients with fibrosis F2–4 vs. F0–1. Trying to improve the predictive value of all NITs, using Youden's methodology, to optimize the suggested cut-off points did not materially improve the results.Conclusions: The validation of currently available NITs using biopsy-proven samples provides new evidence for their ability to differentiate between specific disease stages, histological features, and, most importantly, fibrosis grading. The overall performance of the examined NITs needs to be further improved for applications in the clinic

Liver biopsy-based validation, confirmation and comparison of the diagnostic performance of established and novel non-invasive non-alcoholic fatty liver disease indexes:Results from a large multi-center study

Background: Non-invasive tools (NIT) for non-alcoholic fatty liver disease (NAFLD) screening or diagnosis need to be thoroughly validated using liver biopsies.Purpose: To externally validate NITs designed to differentiate the presence or absence of liver steatosis as well as more advanced disease stages, to confirm fully validated indexes (n = 7 NITs), to fully validate partially validated indexes (n = 5 NITs), and to validate for the first time one new index (n = 1 NIT).Methods: This is a multi-center study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven NAFLD (n = 374, including 237 patients with non-alcoholic steatohepatitis (NASH)) and Controls (n = 81) were recruited. A complete validation analysis was performed to differentiate the presence of NAFLD vs. Controls, NASH vs. NAFL, histological features of NASH, and fibrosis stages.Results: The index of NASH (ION) demonstrated the highest differentiation ability for the presence of NAFLD vs. Controls, with the area under the curve (AUC) being 0.894. For specific histological characterization of NASH, no NIT demonstrated adequate performance, while in the case of specific features of NASH, such as hepatocellular ballooning and lobular inflammation, ION demonstrated the best performance with AUC being close to or above 0.850. For fibrosis (F) classification, the highest AUC was reached by the aspartate aminotransferase to platelet ratio index (APRI) being ~0.850 yet only with the potential to differentiate the severe fibrosis stages (F3, F4) vs. mild or moderate fibrosis (F0–2) with an AUC > 0.900 in patients without T2DM. When we excluded patients with morbid obesity, the differentiation ability of APRI was improved, reaching AUC = 0.802 for differentiating the presence of fibrosis F2–4 vs. F0–1. The recommended by current guidelines index FIB-4 seemed to differentiate adequately between severe (i.e., F3–4) and mild or moderate fibrosis (F0–2) with an AUC = 0.820, yet this was not the case when FIB-4 was used to classify patients with fibrosis F2–4 vs. F0–1. Trying to improve the predictive value of all NITs, using Youden's methodology, to optimize the suggested cut-off points did not materially improve the results.Conclusions: The validation of currently available NITs using biopsy-proven samples provides new evidence for their ability to differentiate between specific disease stages, histological features, and, most importantly, fibrosis grading. The overall performance of the examined NITs needs to be further improved for applications in the clinic

Liver biopsy-based validation, confirmation and comparison of the diagnostic performance of established and novel non-invasive non-alcoholic fatty liver disease indexes:Results from a large multi-center study

Background: Non-invasive tools (NIT) for non-alcoholic fatty liver disease (NAFLD) screening or diagnosis need to be thoroughly validated using liver biopsies.Purpose: To externally validate NITs designed to differentiate the presence or absence of liver steatosis as well as more advanced disease stages, to confirm fully validated indexes (n = 7 NITs), to fully validate partially validated indexes (n = 5 NITs), and to validate for the first time one new index (n = 1 NIT).Methods: This is a multi-center study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven NAFLD (n = 374, including 237 patients with non-alcoholic steatohepatitis (NASH)) and Controls (n = 81) were recruited. A complete validation analysis was performed to differentiate the presence of NAFLD vs. Controls, NASH vs. NAFL, histological features of NASH, and fibrosis stages.Results: The index of NASH (ION) demonstrated the highest differentiation ability for the presence of NAFLD vs. Controls, with the area under the curve (AUC) being 0.894. For specific histological characterization of NASH, no NIT demonstrated adequate performance, while in the case of specific features of NASH, such as hepatocellular ballooning and lobular inflammation, ION demonstrated the best performance with AUC being close to or above 0.850. For fibrosis (F) classification, the highest AUC was reached by the aspartate aminotransferase to platelet ratio index (APRI) being ~0.850 yet only with the potential to differentiate the severe fibrosis stages (F3, F4) vs. mild or moderate fibrosis (F0–2) with an AUC > 0.900 in patients without T2DM. When we excluded patients with morbid obesity, the differentiation ability of APRI was improved, reaching AUC = 0.802 for differentiating the presence of fibrosis F2–4 vs. F0–1. The recommended by current guidelines index FIB-4 seemed to differentiate adequately between severe (i.e., F3–4) and mild or moderate fibrosis (F0–2) with an AUC = 0.820, yet this was not the case when FIB-4 was used to classify patients with fibrosis F2–4 vs. F0–1. Trying to improve the predictive value of all NITs, using Youden's methodology, to optimize the suggested cut-off points did not materially improve the results.Conclusions: The validation of currently available NITs using biopsy-proven samples provides new evidence for their ability to differentiate between specific disease stages, histological features, and, most importantly, fibrosis grading. The overall performance of the examined NITs needs to be further improved for applications in the clinic

Towards elucidating carnosic acid biosynthesis in Lamiaceae: Functional characterization of the three first steps of the pathway in Salvia fruticosa and Rosmarinus officinalis

Carnosic acid (CA) is a phenolic diterpene with anti-tumour, anti-diabetic, antibacterial and neuroprotective properties that is produced by a number of species from several genera of the Lamiaceae family, including Salvia fruticosa (Cretan sage) and Rosmarinus officinalis (Rosemary). To elucidate CA biosynthesis, glandular trichome transcriptome data of S. fruticosa were mined for terpene synthase genes. Two putative diterpene synthase genes, namely SfCPSand SfKSL, showing similarities to copalyl diphosphate synthase and kaurene synthase-like genes, respectively, were isolated and functionally characterized. Recombinant expression in Escherichia coli followed by in vitro enzyme activity assays confirmed that SfCPS is a copalyl diphosphate synthase. Coupling of SfCPS with SfKSL, both in vitro and in yeast, resulted in the synthesis miltiradiene, as confirmed by 1D and 2D NMR analyses (1H, 13C, DEPT, COSY H-H, HMQC and HMBC). Coupled transient in vivo assays of SfCPS and SfKSL in Nicotiana benthamiana further confirmed production of miltiradiene in planta. To elucidate the subsequent biosynthetic step, RNA-Seq data of S. fruticosa and R. officinalis were searched for cytochrome P450 (CYP) encoding genes potentially involved in the synthesis of the first phenolic compound in the CA pathway, ferruginol. Three candidate genes were selected, SfFS, RoFS1 and RoFS2. Using yeast and N. benthamiana expression systems, all three where confirmed to be coding for ferruginol synthases, thus revealing the enzymatic activities responsible for the first three steps leading to CA in two Lamiaceae genera

Insight on genes affecting tuber development in potato upon <i>Potato spindle tuber viroid</i> (PSTVd) infection

Potato (Solanum tuberosum L) is a natural host of Potato spindle tuber viroid (PSTVd) which can cause characteristic symptoms on developing plants including stunting phenotype and distortion of leaves and tubers. PSTVd is the type species of the family Pospiviroidae, and can replicate in the nucleus and move systemically throughout the plant. It is not well understood how the viroid can affect host genes for successful invasion and which genes show altered expression levels upon infection. Our primary focus in this study is the identification of genes which can affect tuber formation since viroid infection can strongly influence tuber development and especially tuber shape. In this study, we used a large-scale method to identify differentially expressed genes in potato. We have identified defence, stress and sugar metabolism related genes having altered expression levels upon infection. Additionally, hormone pathway related genes showed significant up- or down-regulation. DWARF1/DIMINUTO, Gibberellin 7-oxidase and BEL5 transcripts were identified and validated showing differential expression in viroid infected tissues. Our study suggests that gibberellin and brassinosteroid pathways have a possible role in tuber development upon PSTVd infection