Feasibility of social cognitive theory-based fall prevention intervention for people with intellectual disabilities living in group-home.

BACKGROUND: Adults with intellectual disability (ID) have a higher rate of fall events than the general population. Consequently, interventions for reducing fall events and improving health are highly required for individuals with ID. One essential step towards effectively delivering fall prevention interventions among adults with ID involves evaluating their feasibility. This study examined the feasibility of a home-based exercise intervention, supplemented with behavioural change strategies, among individuals with ID living in residential settings. METHOD: This study provided an 8-week intervention, consisting of a workshop for support workers and sessions for participants with ID, focusing on behavioural reward/s, education regarding fall prevention/exercise and exercise training. One week prior to and 1 week following such an intervention, such participants underwent measurements for (1) physical performance, (2) fall efficacy, (3) self-efficacy for activity and (4) social support. RESULTS: Participants having ID (n = 33), support workers (n = 11) and one administrator participated in this study. There were no adverse events during the intervention, and the mean adherence rate was 70.8 ± 19.5%. Two participants with ID dropped out of the programme due to a lack of interest. The participants with ID significantly improved individual physical performance, self-efficacy for activity, fall efficacy and support from friends and support workers. CONCLUSIONS: Fall prevention interventions for adults with ID living in group-homes were highly promising for eventual large-scale implementation within such communities.

Predicting the rate of oxygen uptake from step counts using ActiGraph waist-worn accelerometers in adults with Down syndrome.

BACKGROUND: Step rate predicts ambulatory intensity as reflected in the rate of oxygen uptake (VO2 ) - a measure of energy expenditure. Whether step rate as measured by an accelerometer predicts VO2 in adults with Down syndrome (DS) is unknown. We examined whether step rate predicts VO2 in adults with and without DS. We also developed an equation for predicting VO2 and examined its accuracy. METHOD: Sixteen adults with DS (6 women and 10 men; age 31 ± 15 years) and 19 adults without DS (9 women and 10 men; age 25 ± 6 years) performed standing and walking at their preferred speed, 0.8 and 1.4 m·s-1 . We measured VO2 with a portable spirometer and step rate with a triaxial accelerometer (wGT3X-BT; ActiGraph) on the non-dominant hip, using the low-frequency extension filter. We ran multilevel regression for predicting VO2 from linear and quadratic terms for step rate, group (1 = DS; 0 = non-DS), body mass, height, body mass index (BMI), leg length and sex. We estimated VO2 with the resultant equation and calculated the equation's absolute per cent error, which we compared between groups. RESULTS: VO2 was higher in persons with than without DS only at the fast walking speed (P = 0.018). DS did not predict VO2 . Step rate, step rate squared and BMI were significant predictors of VO2 (P < 0.001; R2  = 0.80). Absolute error across walking speeds was 13.5-18.8% and 11.7-13.4% for adults with and without DS, respectively, and did not differ between groups or speeds. CONCLUSIONS: Step rate, step rate squared and BMI predict VO2 in adults with and without DS. Prediction error does not differ between groups.

Do food and stress biomarkers work for wastewater-based epidemiology? A critical evaluation.

Dietary characteristics and oxidative stress are closely linked to the wellbeing of individuals. In recent years, various urinary biomarkers of food and oxidative stress have been proposed for use in wastewater-based epidemiology (WBE), in efforts to objectively monitor the food consumed and the oxidative stress experienced by individuals in a wastewater catchment. However, it is not clear whether such biomarkers are suitable for wastewater-based epidemiology. This study presents a suite of 30 urinary food and oxidative stress biomarkers and evaluates their applicability for WBE studies. This includes 22 biomarkers which were not previously considered for WBE studies. Daily per capita loads of biomarkers were measured from 57 wastewater influent samples from nine Australian catchments. Stability of biomarkers were assessed using laboratory scale sewer reactors. Biomarkers of consumption of vitamin B2, vitamin B3 and fibre, as well as a component of citrus had per capita loads in line with reported literature values despite susceptibility of degradation in sewer reactors. Consumption biomarkers of red meat, fish, fruit, other vitamins and biomarkers of stress had per capita values inconsistent with literature findings, and/or degraded rapidly in sewer reactors, indicating that they are unsuitable for use as WBE biomarkers in the traditional quantitative sense. This study serves to communicate the suitability of food and oxidative stress biomarkers for future WBE research.

Stomaching the pain of spinal fusion: gastrointestinal discomfort is as severe as back pain in 50% of adolescent idiopathic scoliosis patients following posterior spinal fusion.

PURPOSE: There have been no prospective studies investigating gastrointestinal (GI) symptoms of patients with adolescent idiopathic scoliosis (AIS) following posterior spinal fusion (PSF). The purpose of this study was to evaluate the incidence and severity of self-reported GI symptoms following PSF. METHODS: In all, 40 AIS patients undergoing PSF were prospectively enrolled between March 2015 and October 2016. Patients completed a survey on each postoperative, inpatient day regarding nausea, emesis, constipation, abdominal pain and back pain, rating their pain on a scale of 1 to 10. RESULTS: Abdominal pain (50%), emesis (63%), nausea (65%) and constipation (68%) were experienced by the majority of patients. Of those reporting back pain, the mean pain level during the postoperative period was 5.1 (0.2 to 9.6). Of those reporting abdominal pain, the mean pain level during the postoperative period was 5.5 (1.4 to 8.6), which was not different than the severity of their back-pain levels (mean = 6.0, p = 0.31). CONCLUSIONS: Gastrointestinal issues in AIS patients following PSF are common. Abdominal pain was as severe as the back pain for half of the patients. LEVEL OF EVIDENCE: II.

Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease.

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have gut dysbiosis and intestinal bacterial overgrowth. AIM: To test the hypothesis that endotoxemia is associated with the histological severity of nonalcoholic fatty liver disease (NAFLD) and determine factors associated with endotoxemia. METHODS: The endotoxemia markers lipopolysaccharide-binding protein (LBP) and endotoxin levels were measured in 237 NAFLD patients 1 day before liver biopsy. Biomarkers of liver injury and transient elastography were performed as additional markers of disease severity. RESULTS: A total of 114/237 (48%) patients had NASH and 80/237 (34%) had F2-4 fibrosis. LBP was correlated with lobular inflammation (P=.001), while both LBP (P=.0004) and endotoxin levels (P=0.008) were correlated with fibrosis. LBP was also correlated with cytokeratin-18 fragments (P=.002) and aspartate aminotransferase-to-alanine aminotransferase ratio (P=.006), and both LBP (P=.019) and endotoxin (P=.006) were correlated with liver stiffness measurement by transient elastography. LBP was increased in patients with NASH (15.3±4.6 vs 13.8±3.3 µg/mL; P=.005) and F2-4 fibrosis (15.4±4.4 vs 14.0±3.7 µg/mL; P=.008). Interestingly, patients harbouring the TM6SF2 rs58542926 T allele that predispose to NAFLD/NASH had higher LBP level. By multivariate analysis, gender, higher body mass index and glycated haemoglobin, and TM6SF2 variants were independent factors associated with increased LBP level. CONCLUSIONS: Endotoxemia is positively associated with NASH and significant fibrosis. The association between TM6SF2 and endotoxemia warrants further investigations. The findings may shed light on the pathogenesis of NASH and inform a novel treatment target.

Carotid Webs and Recurrent Ischemic Strokes in the Era of CT Angiography.

BACKGROUND AND PURPOSE: Carotid webs may cause recurrent ischemic stroke. We describe the prevalence, demographics, clinical presentation, imaging features, histopathology, and stroke risk associated with this under-recognized lesion. MATERIALS AND METHODS: A carotid web was defined on CTA as a thin intraluminal filling defect along the posterior wall of the carotid bulb just beyond the carotid bifurcation on oblique sagittal section CTA that was seen as a septum on axial CTA. Using a prospective case series from April 2013 to April 2014, we describe the demographics, spectrum of imaging features on CTA, and histopathology of these carotid webs. From a retrospective analysis of patients at our center from May 2012 to April 2013 who had a baseline head and neck CTA followed by a brain MR imaging within 1-2 days of the CTA, we determine the period prevalence of carotid webs and the prevalence of ipsilateral stroke on imaging. RESULTS: In the prospective series, the mean age was 50 years (range, 41-55 years); 5/7 patients were women. Recurrent stroke was seen in 5/7 (71.4%) patients with the carotid web; time to recurrence ranged from 1 to 97 months. Histopathology suggested a high probability of fibromuscular dysplasia. In the retrospective series, carotid webs were seen in 7/576 patients for a hospital-based-period prevalence of 1.2% (95% CI, 0.4%-2.5%). Two of these 7 patients had acute stroke in the vascular territory of the carotid web. CONCLUSIONS: A carotid web may contribute to recurrent ischemic stroke in patients with no other determined stroke mechanism. Intimal variant fibromuscular dysplasia is the pathologic diagnosis in most cases. The prevalence of carotid web is low, while the optimal management strategy remains unknown.

Atomic scale investigation of non-equilibrium segregation of boron in a quenched Mo-free martensitic steel.

B-added low carbon steels exhibit excellent hardenability. The reason has been frequently attributed to B segregation at prior austenite grain boundaries, which prevents the austenite to ferrite transformation and favors the formation of martensite. The segregation behavior of B at prior austenite grain boundaries is strongly influenced by processing conditions such as austenitization temperatures and cooling rates and by alloying elements such as Mo, Cr, and Nb. Here an local electrode atom probe was employed to investigate the segregation behavior of B and other alloying elements (C, Mn, Si, and Cr) in a Cr-added Mo-free martensitic steel. Similar to our previous results on a Mo-added steel, we found that in both steels B is segregated at prior austenite grain boundaries with similar excess values, whereas B is neither detected in the martensitic matrix nor at martensite-martensite boundaries at the given cooling rate of 30K/s. These results are in agreement with the literature reporting that Cr has the same effect on hardenability of steels as Mo in the case of high cooling rates. The absence of B at martensite-martensite boundaries suggests that B segregates to prior austenite grain boundaries via a non-equilibrium mechanism. Segregation of C at all boundaries such as prior austenite grain boundaries and martensite-martensite boundaries may occur by an equilibrium mechanism.

Guided mass spectrum labelling in atom probe tomography.

Atom probe tomography (APT) is a valuable near-atomic scale imaging technique, which yields mass spectrographic data. Experimental correctness can often pivot on the identification of peaks within a dataset, this is a manual process where subjectivity and errors can arise. The limitations of manual procedures complicate APT experiments for the operator and furthermore are a barrier to technique standardisation. In this work we explore the capabilities of computer-guided ranging to aid identification and analysis of mass spectra. We propose a fully robust algorithm for enumeration of the possible identities of detected peak positions, which assists labelling. Furthermore, a simple ranking scheme is developed to allow for evaluation of the likelihood of each possible identity being the likely assignment from the enumerated set. We demonstrate a simple, yet complete work-chain that allows for the conversion of mass-spectra to fully identified APT spectra, with the goal of minimising identification errors, and the inter-operator variance within APT experiments. This work chain is compared to current procedures via experimental trials with different APT operators, to determine the relative effectiveness and precision of the two approaches. It is found that there is little loss of precision (and occasionally gain) when participants are given computer assistance. We find that in either case, inter-operator precision for ranging varies between 0 and 2 "significant figures" (2σ confidence in the first n digits of the reported value) when reporting compositions. Intra-operator precision is weakly tested and found to vary between 1 and 3 significant figures, depending upon species composition levels. Finally it is suggested that inconsistencies in inter-operator peak labelling may be the largest source of scatter when reporting composition data in APT.

Combining structural and chemical information at the nanometer scale by correlative transmission electron microscopy and atom probe tomography.

In many cases, the three-dimensional reconstructions from atom probe tomography (APT) are not sufficiently accurate to resolve crystallographic features such as lattice planes, shear bands, stacking faults, dislocations or grain boundaries. Hence, correlative crystallographic characterization is required in addition to APT at the exact same location of the specimen. Also, for the site-specific preparation of APT tips containing regions of interest (e.g. grain boundaries) correlative electron microscopy is often inevitable. Here we present a versatile experimental setup that enables performing correlative focused ion beam milling, transmission electron microscopy (TEM), and APT under optimized characterization conditions. The setup was designed for high throughput, robustness and practicability. We demonstrate that atom probe tips can be characterized by TEM in the same way as a standard TEM sample. In particular, the use of scanning nanobeam diffraction provides valuable complementary crystallographic information when being performed on atom probe tips. This technique enables the measurement of orientation and phase maps as known from electron backscattering diffraction with a spatial resolution down to one nanometer.

Effects of meal composition on postprandial incretin, glucose and insulin responses after surgical and medical weight loss.

BACKGROUND: Meal tolerance tests are frequently used to study dynamic incretin and insulin responses in the postprandial state; however, the optimal meal that is best tolerated and suited for hormonal response following surgical and medical weight loss has yet to be determined. OBJECTIVE: To evaluate the tolerability and effectiveness of different test meals in inducing detectable changes in markers of glucose metabolism in individuals who have undergone a weight loss intervention. METHODS: Six individuals who underwent surgical or medical weight loss (two Roux-en-Y gastric bypass, two sleeve gastrectomy and two medical weight loss) each completed three meal tolerance tests using liquid-mixed, solid-mixed and high-fat test meals. The tolerability of each test meal, as determined by the total amount consumed and palatability, as well as fasting and meal-stimulated glucagon-like peptide, glucose-dependent insulinotropic polypeptide, insulin and glucose were measured. RESULTS: Among the six individuals, the liquid-mixed meal was better and more uniformly tolerated with a median meal completion rate of 99%. Among the four bariatric surgical patients, liquid-mixed meal stimulated on average a higher glucagon-like peptide (percent difference: 83.7, 89), insulin secretion (percent difference: 155.1, 158.7) and glucose-dependent insulinotropic polypeptide (percent difference: 113.5, 34.3) compared with solid-mixed and high-fat meals. CONCLUSIONS: The liquid-mixed meal was better tolerated with higher incretin and insulin response compared with the high-fat and solid-mixed meals and is best suited for the evaluation of stimulated glucose homeostasis.

Small bowel resection induces long-term changes in the enteric microbiota of mice.

PURPOSE: The enteric microbiome is known to play a major role in healthy gut homeostasis and several disease states. It may also contribute to both the intestinal recovery and complications that occur in patients with short bowel syndrome. The extent and nature of alterations to the gut microbiota following intestinal resection, however, are not well studied in a controlled setting. The purpose of this investigation is to characterize the effects of massive small bowel resection on the murine enteric microflora. METHODS: Wild-type C57BL6 mice, following a week of acclamation to a liquid rodent diet, underwent either 50% proximal small bowel resection (SBR) or a sham operation. Mice were sacrificed, and enteric contents from the small bowel, cecum, and stool were harvested at 7 and 90 days post-operatively. DNA was isolated, and the V3-V5 regions of the 16s rRNA gene amplified and pyrosequenced on a Roche 454 platform. Sequences were clustered into operation taxonomic units and classified. Communities were then analyzed for diversity and phylogenic composition. RESULTS: In the long-term group, the microbes inhabiting the ileum of mice undergoing SBR and sham operation differed significantly at the genus level (p < 0.001). Small bowel contents collected before and after SBR also differed significantly (p = 0.006). This was driven by an increase in Lactobacillus and decrease in Enterobacteriaceae species in mice undergoing SBR. No difference was seen in the long-term stool or in stool, cecal, or ileal contents in the short-term. No difference in microbial community diversity was found in any group. CONCLUSION: Bowel resection induces long-term changes in the microbial community of the murine ileum, but not at more distal sites of the gastrointestinal tract. The increase in Lactobacillus encountered small bowel of resected mice correlates with limited previous studies. These changes may reflect an adaptive response of the microbiota to maximize energy extraction, but further studies are needed to establish the role played by this altered community.

Atomic-scale quantification of grain boundary segregation in nanocrystalline material.

Grain boundary segregation leads to nanoscale chemical variations that can alter a material's performance by orders of magnitude (e.g., embrittlement). To understand this phenomenon, a large number of grain boundaries must be characterized in terms of both their five crystallographic interface parameters and their atomic-scale chemical composition. We demonstrate how this can be achieved using an approach that combines the accuracy of structural characterization in transmission electron microscopy with the 3D chemical sensitivity of atom probe tomography. We find a linear trend between carbon segregation and the misorientation angle ω for low-angle grain boundaries in ferrite, which indicates that ω is the most influential crystallographic parameter in this regime. However, there are significant deviations from this linear trend indicating an additional strong influence of other crystallographic parameters (grain boundary plane, rotation axis). For high-angle grain boundaries, no general trend between carbon excess and ω is observed; i.e., the grain boundary plane and rotation axis have an even higher influence on the segregation behavior in this regime. Slight deviations from special grain boundary configurations are shown to lead to unexpectedly high levels of segregation.

Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B--a prospective cohort study with paired transient elastography examinations.

BACKGROUND: Metabolic syndrome is a known risk factor of cirrhosis in chronic hepatitis B (CHB). AIM: To investigate the effects of coincidental metabolic syndrome on liver fibrosis progression in treatment-naïve CHB patients. METHODS: A total of 1466 CHB patients underwent liver stiffness measurement (LSM) by transient elastography in 2006-2008; 663 patients remained treatment-naïve and had second LSM in 2010-2012. Liver fibrosis progression was defined as an increase in LSM ≥30% at the second assessment. The impact of coincidental metabolic syndrome and its factors on liver fibrosis progression were evaluated after adjustment for viral load and hepatitis activity. RESULTS: At baseline, the mean age was 43 ± 12 years, 55% were males, serum alanine aminotransferase (ALT) was 44 ± 40 IU/L, HBV DNA was 4.0 ± 2.0 log IU/mL and LSM was 6.3 ± 3.6 kPa. Metabolic syndrome was diagnosed in 80 (12%) and 142 (21%) patients at baseline and follow-up visit, respectively; 84 (13%) and 22 (3%) patients had coincidental and resolved metabolic syndrome respectively. After an interval of 44 ± 7 months, 107 (16%) patients developed liver fibrosis progression. Coincidental metabolic syndrome [adjusted odds ratio (aOR) 2.0, 95% confidence interval (CI) 1.1-3.5, P = 0.015], central obesity (aOR 2.0, 95% CI 1.0-4.1, P = 0.05) and low level of high-density lipoprotein cholesterol (aOR 1.9, 95% CI 1.0-3.7, P = 0.04) were associated with liver fibrosis progression independent of change in viral load and ALT level. The effects of coincidental metabolic syndrome were most apparent in the immune-tolerant phase. CONCLUSION: Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B infection, independent of viral load and hepatitis activity.

PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome.

BACKGROUND: The rs738409 GG variant in patatin-like phospholipase 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if it contributes to the development of NAFLD through affecting dietary pattern. AIM: To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD. METHODS: Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food-frequency questionnaire. RESULTS: The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern. CONCLUSIONS: The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.

Non-invasive algorithm of enhanced liver fibrosis and liver stiffness measurement with transient elastography for advanced liver fibrosis in chronic hepatitis B.

BACKGROUND: The accuracy of Enhanced Liver Fibrosis (ELF; ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) in assessing liver fibrosis in chronic hepatitis B (CHB) is to be determined. AIM: To derive and validate a combined ELF-liver stiffness measurement (LSM) algorithm to predict advanced fibrosis in CHB patients. METHODS: Using the data of a previously reported cohort of 238 CHB patients, an ALT-based LSM algorithm for liver fibrosis was used as a training cohort to evaluate the performance of ELF against liver histology. The best combined ELF-LSM algorithm was then validated in new cohort of 85 CHB patients not previously reported. RESULTS: In the training cohort, LSM has better performance of diagnosing advanced (≥F3) fibrosis (area under the receiver operating characteristics curve [AUROC] 0.83, 95% confidence interval [CI 0.76-0.91] than ELF (AUROC 0.69, 95% CI 0.63-0.75). The optimal cut-off values of ELF were 8.4 to exclude advanced fibrosis, and 10.8 to confirm advanced fibrosis. In the training cohort, an ELF ≤ 8.4 had a sensitivity of 95% to exclude advanced fibrosis; an ELF > 10.8 had a specificity of 92% to confirm advanced fibrosis. In the combined algorithm, low ELF or low LSM could be used to exclude advanced fibrosis as both of them had high sensitivity (≥90%). To confirm advanced fibrosis, agreement between high ELF and high LSM could improve the negative predictive value specificity (from 65% and 74% to 80%). CONCLUSIONS: An Enhanced Liver Fibrosis - liver stiffness measurement algorithm could improve the accuracy of prediction of either ELF or LSM alone. Liver biopsy could be correctly avoided in approximately 60% of patients.