Plusoptix photoscreener use for paediatric vision screening in Flanders and Iran

Purpose Photoscreening assesses risk factors for amblyopia, as an alternative to measurement of visual acuity (VA) to detect amblyopia, on the premise that its early correction could prevent development of amblyopia. We studied implementations of Plusoptix photoscreening in existing population-based screening in Flanders and Iran. Methods In Flanders, VA is measured at age 3, 4 and 6, photoscreening was added to existing screening at age 1 and 2.5 years in 2013. In Iran, VA is measured at ages 3-6 years, photoscreening was added at ages 3-6 years between 2011-2016. Plusoptix use was analyzed in the literature for detection of risk factors for amblyopia and amblyopia itself, for ages 0-3 and for 4-6. A questionnaire, containing seven domains: existing vision screening, addition of photoscreening, implementation in screening program, training, attendance, diagnosis and treatment, and costs was distributed. In Iran, screening procedures were observed on site. Results Implementation of Plusoptix photoscreening was mainly analyzed from questionnaires and interviews, its effectiveness from literature data. In Flanders, of 56,759 children photoscreened at age one (81% of children born in 2013), 9.2% had been referred,13% of these were treated, mostly with glasses, resulting in an increase of 4-year old children wearing glasses from 4.7% to 6.4%. In Iran, 90% of children aged 3-6 years participated in vision screening in 2016, but only those who failed the vision test were subjected to photoscreening. Conclusions In Flanders, the use of Plusoptix photoscreening at ages 1 and 2.5 resulted in an increase of children wearing glasses, but it remains unknown how many cases of amblyopia have been prevented. Studies are needed to determine the relation between size and sort of refractive error and strabismus, and the increased chance to develop amblyopia

Design of a web-based LBS framework addressing usability, cost, and implementation constraints

This research investigates barriers that prevent Location Based Services (LBS) from reaching its full potential. The different constraints, including poor usability, lack of positioning support, costs, and integration difficulties are highlighted. A framework was designed incorporating components based on existing and new technologies that could help address the constraints of LBS and increase end-user acceptance. This research proposes that usability constraints can be addressed by adapting a system to user characteristics which are inferred on the basis of captured user context and interaction data. A prototype LBS system was developed to prove the feasibility and benefit of the framework design, demonstrating that constraints of positioning, cost, and integration can be overcome. Volunteers were asked to use the system, and to answer questions in relation to their proficiency and experience. User-feedback showed that the proposed combination of functionality was well-received, and the prototype was appealing to many users. Ground-truths from the survey were related back to data captured with a user monitoring component in order to investigate whether users can be classified according to their context and how they interact. The results have shown that statistically significant relationships exist, and that by using the C4.5 decision-tree, computer proficiency can be estimated within one class-width in 76.7% of the cases. These results suggest that it may be possible to build a user-model to estimate computer proficiency on the basis of user-interaction data. The user model could then used to improve usability through adaptive user-specific customisations

Consistency of metabolic responses and appetite sensations under postabsorptive and postprandial conditions

The present study aimed to investigate the reliability of metabolic and subjective appetite responses under fasted conditions and following consumption of a cereal-based breakfast. Twelve healthy, physically active males completed two postabsorption (PA) and two postprandial (PP) trials in a randomised order. In PP trials a cereal based breakfast providing 1859 kJ of energy was consumed. Expired gas samples were used to estimate energy expenditure and fat oxidation and 100 mm visual analogue scales were used to determine appetite sensations at baseline and every 30 min for 120 min. Reliability was assessed using limits of agreement, coefficient of variation (CV), intraclass coefficient of correlation and 95% confidence limits of typical error. The limits of agreement and typical error were 292.0 and 105.5 kJ for total energy expenditure, 9.3 and 3.4 g for total fat oxidation and 22.9 and 8.3 mm for time-averaged AUC for hunger sensations, respectively over the 120 min period in the PP trial. The reliability of energy expenditure and appetite in the 2 h response to a cereal-based breakfast would suggest that an intervention requires a 211 kJ and 16.6 mm difference in total postprandial energy expenditure and time-averaged hunger AUC to be meaningful, fat oxidation would require a 6.7 g difference which may not be sensitive to most meal manipulations

Postprandial Energy Metabolism in the Regulation of Body Weight: Is there a Mechanistic Role for Dietary Calcium?

There has been much interest in the mechanisms by which calcium may attenuate weight gain or accelerate body fat loss. This review focuses on postprandial energy metabolism and indicates that dietary calcium increases whole body fat oxidation after single and multiple meals. There is, as yet, no conclusive evidence for a greater diet induced thermogenesis, an increased lipolysis or suppression of key lipogenic enzyme systems. There is however convincing evidence that higher calcium intakes promote a modest energy loss through increased fecal fat excretion. Overall, there is a role for dietary calcium in human energy metabolism. Future studies need to define threshold intakes for metabolic and gastrointestinal outcomes

Long-term follow-up of retinal degenerations associated with LRAT mutations and their comparability to phenotypes associated with RPE65 mutations

Purpose: To investigate the natural history in patients with LRAT-associated retinal degenerations (RDs), in the advent of clinical trials testing treatment options. Methods: A retrospective cohort of 13 patients with LRAT-RDs. Results: Twelve patients from a genetic isolate carried a homozygous c.12del mutation. One unrelated patient carried a homozygous c.326G>T mutation. The mean follow-up time was 25.3 years (SD 15.2; range 4.8-53.5). The first symptom was nyctalopia (n = 11), central vision loss (n = 1), or light-gazing (n = 1), and was noticed in the first decade of life. Seven patients (54%) reached low vision (visual acuity < 20/67), four of whom reaching blindness (visual acuity < 20/400), respectively, at mean ages of 49.9 (SE 5.4) and 59.9 (SE 3.1) years. The fundus appearance was variable. Retinal white dots were seen in six patients (46%). Full-field electroretinograms (n = 11) were nondetectable (n = 2; ages 31-60), reduced in a nonspecified pattern (n = 2; ages 11-54), or showed rod-cone (n = 6; ages 38-48) or cone-rod (n = 1; age 29) dysfunction. Optical coherence tomography (n = 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second (n = 1) and sixth decade of life (n = 2), and profound chorioretinal degeneration from the eighth decade of life (n = 1). Conclusions: LRAT-associated phenotypes in this cohort were variable and unusual, but generally milder than those seen in RPE65-associated disease, and may be particularly amenable to treatment. The window of therapeutic opportunity can be extended in patients with a mild phenotype. Translational Relevance: Knowledge of the natural history of LRAT-RDs is essential in determining the window of opportunity in ongoing and future clinical trials for novel therapeutic options

Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG

Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study

Introduction: Guidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia. Methods: A prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured. Results: Of 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bedside characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 mu g/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia. The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R-2 = 0.278, P = 0.007). Conclusions: PCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.Immunogenetics and cellular immunology of bacterial infectious disease

Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG

Blockade of the BLT1-LTB4 axis does not affect mast cell migration towards advanced atherosclerotic lesions in LDLr-/- mice

Mast cells have been associated with the progression and destabilization of advanced atherosclerotic plaques. Reducing intraplaque mast cell accumulation upon atherosclerosis progression could be a potent therapeutic strategy to limit plaque destabilization. Leukotriene B4 (LTB4) has been reported to induce mast cell chemotaxis in vitro. Here, we examined whether antagonism of the LTB4-receptor BLT1 could inhibit mast cell accumulation in advanced atherosclerosis. Expression of genes involved in LTB4 biosynthesis was determined by single-cell RNA sequencing of human atherosclerotic plaques. Subsequently, Western-type diet fed LDLr-/- mice with pre-existing atherosclerosis were treated with the BLT1-antagonist CP105,696 or vehicle control three times per week by oral gavage. In the spleen, a significant reduction in CD11b+ myeloid cells was observed, including Ly6Clo and Ly6Chi monocytes as well as dendritic cells. However, atherosclerotic plaque size, collagen and macrophage content in the aortic root remained unaltered upon treatment. Finally, BLT1 antagonism did not affect mast cell numbers in the aortic root. Here, we show that human intraplaque leukocytes may be a source of locally produced LTB4. However, BLT1-antagonism during atherosclerosis progression does not affect either local mast cell accumulation or plaque size, suggesting that other mechanisms participate in mast cell accumulation during atherosclerosis progression.Biopharmaceutic