The Benefit of Detecting Reduced Intracellular B12 Activity through Newborn Screening Remains Unclear

Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable

Post-mortem magnetic resonance imaging with computed tomography-guided biopsy for foetuses and infants: a prospective, multicentre, cross-sectional study

BACKGROUND: Post-mortem imaging has been suggested as an alternative to conventional autopsy in the prenatal and postnatal periods. Noninvasive autopsies do not provide tissue for histological examination, which may limit their clinical value, especially when infection-related morbidity and mortality are suspected. METHODS: We performed a prospective, multicentre, cross-sectional study to compare the diagnostic performance of post-mortem magnetic resonance imaging with computed tomography-guided biopsy (Virtopsy®) with that of conventional autopsy in foetuses and infants. Cases referred for conventional autopsy were eligible for enrolment. After post-mortem imaging using a computed tomography scanner and a magnetic resonance imaging unit, computed tomography-guided tissue sampling was performed. Virtopsy results were compared with conventional autopsy in determining the likely final cause of death and major pathologies. The primary outcome was the proportion of cases for which the same cause of death was determined by both methods. Secondary outcomes included the proportion of false positive and false negative major pathological lesions detected by virtopsy and the proportion of computed tomography-guided biopsies that were adequate for histological examination. RESULTS: Overall, 101 cases (84 fetuses, 17 infants) were included. Virtopsy and autopsy identified the same cause of death in 91 cases (90.1%, 95% CI 82.7 to 94.5). The sensitivity and specificity of virtopsy for determining the cause of death were 96.6% (95% CI 90.6 to 98.8) and 41.7% (95% CI 19.3 to 68.0), respectively. In 32 cases (31.7%, 95% CI 23.4 to 41.3), major pathological findings remained undetected by virtopsy, and in 45 cases (44.6%, 95% CI 35.2 to 54.3), abnormalities were diagnosed by virtopsy but not confirmed by autopsy. Computed tomography-guided tissue sampling was adequate for pathological comments in 506 of 956 biopsies (52.7%) and added important diagnostic value in five of 30 cases (16.1%) with an unclear cause of death before autopsy compared with postmortem imaging alone. In 19 of 20 infective deaths (95%), biopsies revealed infection-related tissue changes. Infection was confirmed by placental examination in all fetal cases. CONCLUSIONS: Virtopsy demonstrated a high concordance with conventional autopsy for the detection of cause of death but was less accurate for the evaluation of major pathologies. Computed tomography-guided biopsy had limited additional diagnostic value. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01888380)

Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991-2003: methods and characterization of participants

Summary.: Objectives: The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was designed to investigate the health effects from long-term exposure to air pollution. Methods: The health assessment at recruitment (1991) and at the first reassessment (2001-3) consisted of an interview about respiratory health, occupational and other exposures, spirometry, a methacholine bronchial challenge test, end-expiratory carbon monoxide (CO) measurement and measurement for atopy. A bio bank for DNA and blood markers was established. Heart rate variability was measured using a 24-hour ECG (Holter) in a random sample of participants aged 50years and older. Concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and particulates in ambient air have been monitored in all study areas since 1991. Residential histories collected over the 11year follow-up period coupled with GIS modelling will provide individual long-term air pollutant exposure estimates. Results: Of 9651 participants examined in 1991, 8715 could be traced for the cohort study and 283 died. Basic information about health status was obtained for 8047 individuals (86% of alive persons), 6528 individuals (70%) agreed to the health examination and 5973 subjects (62%) completed the entire protocol. Non-participants in the reassessment were on average younger than participants and more likely to have been smokers and to have reported respiratory symptoms in the first assessment. Average weight had increased by 5.5kg in 11years and 28% of smokers in 1991 had quit by the time of the reassessmen

A school-based physical activity program to improve health and fitness in children aged 6–13 years ("Kinder-Sportstudie KISS"): study design of a randomized controlled trial [ISRCTN15360785]

BACKGROUND: Childhood obesity is the result of a long lasting imbalance between energy intake and energy expenditure. A major contributing factor is physical inactivity which is closely linked to bone health, cardiovascular disease risk, fitness and psychological factors. The school seems to provide an excellent setting to enhance levels of physical activity (PA). However, there is insufficient data from previous school-based intervention trials on how to enhance overall PA. It is also unknown whether an intervention aimed at increasing PA is effective in improving the children's health. The purpose of this paper is to outline the design of a school-based randomized, controlled trial (RCT) aiming to increase overall PA and to improve fitness and health in 6- to 13-year-old children. METHODS/DESIGN: 15 schools were randomized to the intervention (n = 9) or the control (n = 6) group, stratified by geographic region (urban vs. rural) and by age (1(st )and 5(th )grade). Participation was given for all children in the intervention group since in this group the intervention was part of the normal school curriculum. The intervention during one academic year consisted of: 1. two additional physical education classes per week given by trained physical education teachers adding up to a total of five PA classes per week, 2. short PA breaks (2–5 min each) during academic lessons, 3. PA home work, and 4. adaptation of recreational areas around the school. All children underwent anthropometric measurements, blood pressure assessment, fitness testing, measurement of PA and they filled out questionnaires. At least 70% of all children agreed to blood sampling and measurements of body composition and bone mineral measurements by dual energy x-ray absorptiometry. The primary endpoints of the study after one year were an increase in total PA by accelerometry, an increase in aerobic fitness measured by the 20 m shuttle run, a decrease in percent body fat derived from skinfold measurements and an increase in quality of life as assessed by the child health questionnaire in the intervention group compared to the control group. Secondary outcomes were overall fitness, differences in body composition including body fat distribution, cardiovascular risk factors, psychosocial health, bone mineral content and density of femur, lumbar spine and total body and food intake. DISCUSSION: Our preliminary data suggest that the children were representative of Swiss children with respect to sex, socio-demographic status, and body mass index. Short-term results can be expected by the beginning of 2007. We hypothesized that our intervention will lead to an increase in PA, fitness and overall health. Based on our data, we aim to provide important information regarding the influence of such an intervention on these outcome measures in school-aged children and to provide nationwide guidelines to improve PA in children

Topology of the microsomal glycerol-3-phosphate acyltransferase Gpt2p/Gat1p of Saccharomyces cerevisiae

All glycerophospholipids are made from phosphatidic acid, which, according to the traditional view, is generated at the cytosolic surface of the ER. In yeast, phosphatidic acid is synthesized de novo by two acyl-CoA dependent acylation reactions. The first is catalyzed by one of the two homologous glycerol-3-phosphate acyltransferases Gpt2p/Gat1p and Sct1p/Gat2p, the second by one of the two 1-acyl-sn-glycerol-3-phosphate acyltransferases Slc1p and Ale1p/Slc4p. To study the biogenesis and topology of Gpt2p we observed the location of dual topology reporters inserted after various transmembrane helices. Moreover, using microsomes, we probed the accessibility of natural and substituted cysteine residues to a membrane impermeant alkylating agent and tested the protease sensitivity of various epitope tags inserted into Gpt2p. Finally, we assayed the sensitivity of the acyltransferase activity to membrane impermeant agents targeting lysine residues. By all these criteria we find that the most conserved motifs of Gpt2p and its functionally relevant lysines are oriented towards the ER lumen. Thus, the first step in biosynthesis of phosphatidic acid in yeast seems to occur in the ER lumen and substrates may have to cross the ER membrane

Stereotactic Image-Guided Microwave Ablation of Hepatocellular Carcinoma using a computer-assisted navigation system.

BACKGROUND & AIMS Ablation plays an important role in the treatment of hepatocellular carcinoma. Because image-guided navigation technology has recently entered the clinical setting, we aimed to analyze its safety, therapeutic and procedural efficiency. METHODS Retrospective analysis of patients treated with stereotactic image-guided microwave ablation between 01/2015 and 12/2017. Interventions were performed using computertomography-guidance with needle trajectory, ablation planning and automatic single-marker patient registration. Needle placement and ablation coverage was controlled by image fusion under general anesthesia with jet-ventilation. RESULTS In total 174 ablations were performed in 88 patients during 119 interventions. Mean age was 66 (46-84) years, 74 (84.1%) were men and 74% were Child Pugh Class A. Median tumor size was 16 (4-45) mm, 62.2% were BCLC A. Median lateral and longitudinal error of needle placement were 3.2 (0.2-14.1) and 1.6 (0-15.8) mm. Median one tumor (1-4) was ablated per session. One patient developed a Dindo IIIb (0.8%) complication, 6 minor complications. After re-ablation of 12 lesions, an efficacy rate of 96.3% was achieved. Local tumor progression was 6.3% (11/174). Close proximity to major vessels was significantly correlated with local tumor progression (p<0.05). Median overall follow-up was 17.5 months after intervention and 24 months after initial diagnosis. BCLC stage, child class and previous treatment were significantly correlated with overall survival (p<0.05). CONCLUSION Stereotactic image-guided microwave ablation is a safe and efficient treatment for HCC offering a curative treatment approach in general and in particular for lesions not detectable on conventional imaging or untreatable due to difficult anatomic locations. This article is protected by copyright. All rights reserved

The Benefit of Detecting Reduced Intracellular B12 Activity through Newborn Screening Remains Unclear

Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable