Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease

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An exploration of the disease burden due to Cryptosporidium in consumed surface water for sub-Saharan Africa

The protozoan pathogen Cryptosporidium is an important cause of diarrhoeal disease, but in many contexts its burden remains uncertain. The Global Waterborne Pathogen model for Cryptosporidium (GloWPa-Crypto) predicts oocyst concentrations in surface water at 0.5 by 0.5° (longitude by latitude) resolution, allowing us to assess the burden specifically associated with the consumption of contaminated surface water at a large scale. In this study, data produced by the GloWPa-Crypto model were used in a quantitative microbial risk assessment (QMRA) for sub-Saharan Africa, one of the regions most severely affected by diarrhoeal disease. We first estimated the number of people consuming surface water in this region and assessed both direct consumption and consumption from a piped (treated) supply. The disease burden was expressed in disability adjusted life years (DALYs). We estimate an annual number of 4.3 × 10⁷ (95% uncertainty interval [UI] 7.4 × 10⁶–5.4 × 10⁷) cases which represent 1.6 × 10⁶ (95% UI 3.2 × 10⁵–2.3 × 10⁶) DALYs. Relative disease burden (DALYs per 100,000 persons) varies widely, ranging between 1.3 (95% UI 0.1–5.7) for Senegal and 1.0 × 10³ (95% UI 4.2 × 10²–1.4 × 10³) for Eswatini. Countries that carry the highest relative disease burden are primarily located in south and south-east sub-Saharan Africa and are characterised by a relatively high HIV/AIDS prevalence. Direct surface water consumption accounts for the vast majority of cases, but the results also point towards the importance of stable drinking water treatment performance. This is, to our knowledge, the first study to utilise modelled data on pathogen concentrations in a large scale QMRA. It demonstrates the potential value of such data in epidemiological research, particularly regarding disease aetiology.     

High resolution SNP array profiling identifies variability in retinoblastoma genome stability

Both hereditary and nonhereditary retinoblastoma (Rb) are commonly initiated by loss of both copies of the retinoblastoma tumor suppressor gene (RB1), while additional genomic changes are required for tumor initiation and progression. Our aim was to determine whether there is genomic heterogeneity between different clinical Rb subtypes. Therefore, 21 Rb tumors from 11 hereditary patients and 10 nonhereditary Rb patients were analyzed using high‐resolution single nucleotide polymorphism (SNP) arrays and gene losses and gains were validated with Multiplex Ligation‐dependent Probe Amplification. In these tumors only a few focal aberrations were detected. The most frequent was a focal gain on chromosome 2p24.3, the minimal region of gain encompassing the oncogene MYCN. The genes BAZ1A, OTX2, FUT8, and AKT1 were detected in four focal regions on chromosome 14 in one nonhereditary Rb. There was a large difference in number of copy number aberrations between tumors. A subset of nonhereditary Rbs turned out to be the most genomic unstable, while especially very young patients with hereditary Rb display stable genomes. Established Rb copy number aberrations, including gain of chromosome arm 1q and loss of chromosome arm 16q, turned out to be preferentially associated with the nonhereditary Rbs with later age of diagnosis. In contrast, copy number neutral loss of heterozygosity was detected mainly on chromosome 13, where RB1 resides, irrespective of hereditary status or age. Focal amplifications and deletions and copy number neutral loss of heterozygosity besides chromosome 13 appear to be rare events in retinoblastoma. © 2013 Wiley Periodicals, Inc.     

Skinfold measurements in children with cystic fibrosis: monitoring fat-free mass and exercise effects

Monitoring fat free mass (FFM), an indicator of nutritional status and a predictor of exercise performance in children, is particularly important in patients with cystic fibrosis (CF). We assessed validity of the skinfold method for measuring FFM, and its changes with exercise training, in children with CF. A total of 14 children with moderately severe symptoms of CF (age 10–18 years) were followed longitudinally and measured three times, before (at 0 and 6 months) and after exercise training (at 12 months). Separately, single measurements were conducted in 12 children with mild symptoms of CF and in 13 healthy controls. FFM was calculated from four skinfold measurements, and compared with estimations from total body water measured with deuterium dilution. The FFM calculated from skinfolds was 1.7% (P < 0.05) and 3.3% (P < 0.005) higher than that estimated with deuterium oxide dilution in patients with CF and controls, respectively. Limits of agreement were similar in patients with moderate and mild symptoms and in controls. The measurements in patients with moderate symptoms showed similar bias and limits of agreement at 6 and 12 months as compared to 0 months. Changes in FFM measured with both methods were significantly correlated before exercise (r = 0.82, P < 0.0005), and after exercise training (r = 0.60, P < 0.05). Conclusion In children with cystic fibrosis, skinfold measurements are applicable to monitor fat free mass irrespective of clinical severity of the disease, and repeated measurements at intervals of 6 months are applicable to monitor changes in fat free mass during exercise training. Received: 15 September 1998 / Accepted in revised form: 22 February 1999     

The relationship between cadence,pedalling technique and gross efficiency in cycling

Technique and energy saving are two variables often considered as important for performance in cycling and related to each other. Theoretically, excellent pedalling technique should give high gross efficiency (GE). The purpose of the present study was to examine the relationship between pedalling technique and GE. 10 well-trained cyclists were measured for GE, force effectiveness (FE) and dead centre size (DC) at a work rate corresponding to ~75% of VO₂max during level and inclined cycling, seat adjusted forward and backward, at three different cadences around their own freely chosen cadence (FCC) on an ergometer. Within subjects, FE, DC and GE decreased as cadence increased (p < 0.001). A strong relationship between FE and GE was found, which was to great extent explained by FCC. The relationship between cadence and both FE and GE, within and between subjects, was very similar, irrespective of FCC. There was no difference between level and inclined cycling position. The seat adjustments did not affect FE, DC and GE or the relationship between them. Energy expenditure is strongly coupled to cadence, but force effectiveness, as a measure for pedalling technique, is not likely the cause of this relationship. FE, DC and GE are not affected by body orientation or seat adjustments, indicating that these parameters and the relationship between them are robust to coordinative challenges within a range of cadence, body orientation and seat position that is used in regular cycling.