Adrenoleukodystrophy in Norway: High Rate of De Novo Mutations and Age-Dependent Penetrance

To investigate X-linked adrenoleukodystrophy in an unselected population, we performed a population based, cross-sectional prevalence study, supplemented by a retrospective study of deceased subjects. Sixty-three subjects (34 males, 29 females) belonging to 22 kindreds were included. Thirty-nine subjects (13 males, 26 females) were alive, and 24 (21 males, 3 females) were deceased on the prevalence day. The point prevalence of X-linked adrenoleukodystrophy in Norway on July 1, 2011, was 0.8 per 100,000 inhabitants. The incidence at birth in the period 1956-1995 was 1.6 per 100,000 inhabitants. An age-dependent penetrance was observed among males and females, with more severe phenotypes appearing with rising age. Only 5% of deceased males had not developed cerebral leukodystrophy. No female older than 50 years was neurologically intact. Sixteen mutations in the ABCD1 gene were identified. De novo mutations were found in 19% of probands. The frequency of X-linked adrenoleukodystrophy was lower in Norway than reported in the literature. A more severe natural course than previously reported was observed, indicating a need for better follow-up of both male and female patients. Given the high rate of de novo mutations, identification programs such as newborn screening may be required to offer timely treatment to all patients.     

The association between physical fitness level and number and severity of injury and illness in youth elite athletes

Youth elite athletes often double their training and competition load after enrollment into specialized sport academy high school programs. The least fit athletes may be exposed to an excessive and too rapid increase in training load, with negative adaptations such as injury and illness as a consequence. In this study, our aim was to determine whether these least fit athletes were at greater risk of injury or illness during their first school year. Participants were 166 youth elite athletes (72% boys) from a variety of team, technical, and endurance sports newly enrolled into specialized sport academy high schools. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used to self‐report injuries and illnesses weekly for 26 weeks. Athletes completed the Ironman Jr physical fitness test battery at baseline, evaluating endurance, strength, agility, and speed properties. We ranked the athletes based on their combined test scores and identified the least fit quartile. The main outcome was the number and severity of health problems, comparing the least fit quartile of athletes to the rest of the cohort. Overall, the least fit quartile of athletes did not report more health problems (mean 3.7, 95% CI 3.0‐4.4) compared with the rest of the cohort (3.6, 3.2‐3.9). In conclusion, we demonstrated no association between low physical fitness level and number and severity of injury and illness in youth elite athletes after enrollment into a specialized sport academy high school program.     

Oxidative Stress in Adults with Autism Spectrum Disorder: A Case Control Study

Journal of Autism and Developmental Disorders - Oxidative stress has been proposed as being important in the pathophysiology of autism spectrum disorders (ASD), and heightened levels of oxidative...     

Perception of longitudinal body axis in microgravity during parabolic flight

It has been proposed that an internal representation of body vertical has a prominent role in spatial orientation. This investigation investigated the ability of human subjects to accurately locate their longitudinal body axis (an imaginary straight body midline running from head to toes) while free-floating in microgravity. Subjects were tested in-flight, as well as on ground in normal gravity in both the upright and supine orientations to provide baseline measurements. The subjects wore a goggle device and were in total darkness. They used knobs to rotate two luminous lines until they were parallel to the subjective direction of their longitudinal body axis, in the roll (right/left) and the pitch (forward/backward) planes. Results showed that the error between the perceived and the objective direction of the longitudinal body axis was significantly larger in microgravity than in normal gravity. This error in this egocentric frame of reference is presumably due to the absence of somatosensory cues when free-floating. Mechanical pressure on the chest using an airbag reduced the error in perception of the longitudinal body axis in microgravity, thus improving spatial orientation.     

In-vivo evaluation of convex array synthetic aperture imaging

This paper presents an in-vivo study of synthetic transmit aperture (STA) imaging in comparison with conventional imaging, evaluating whether STA imaging is feasible in-vivo and whether the image quality obtained is comparable with traditional scanned imaging in terms of penetration depth, spatial resolution, contrast resolution and artifacts. Acquisition was performed using our research scanner RASMUS and a 5.5 MHz convex array transducer. STA imaging was acquired using circular wave emulation by 33-element subapertures and a 20 micros linear FM signal as excitation pulse. For conventional imaging, a 64 element aperture was used in transmit and receive with a 1.5 cycle sinusoid excitation pulse. Conventional and STA images were acquired interleaved, ensuring that the exact same anatomical location was scanned. Image sequences were recorded in real time and processed off-line. Seven male volunteers were scanned abdominally and the resulting images were compared by three medical doctors using randomized blinded presentation. Penetration and image quality were scored and evaluated statistically. Results showed slightly but significantly (0.48 cm, p = 0.008) increased penetration using STA. Image quality was also highly significantly (p < 0.001) increased. Results show that in-vivo ultrasound imaging using STA is feasible for abdominal imaging without severe motion artifacts.     

Intravenous immunoglobulin significantly reduces exposure of concomitantly administered anti‐C5 monoclonal antibody tesidolumab

Awareness of drug‐drug interactions is critical in organ transplant recipient management. However, biologic agents interfering with monoclonal antibodies is not widely considered. We report the effect of high‐dose intravenous immunoglobulin (IVIg) on safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the human anti‐C5 monoclonal antibody tesidolumab (LFG316) in end‐stage renal disease patients awaiting kidney transplant. In this single‐center, phase 1, open‐label, parallel‐group study, 8 patients were assigned to receive either single‐dose tesidolumab + IVIg or tesidolumab alone, with 56‐day follow‐up. Within‐group PK parameters were consistent. Mean tesidolumab exposure decreased 34%, clearance increased 63%, and half‐life decreased 41% comparing tesidolumab + IVIg to tesidolumab alone. IVIg influence on tesidolumab elimination was most evident in the first 3 weeks. Complete suppression of both total and alternative complement activities was maintained for 4 weeks in the tesidolumab alone group and for 2 weeks in the tesidolumab + IVIg group. Tesidolumab was well tolerated. IVIg infused before tesidolumab affected tesidolumab PK and PD, resulting in a shortened period of full complement activity inhibition. These findings suggest a clinically relevant impact of IVIg on monoclonal antibody clearance and indirectly hint at an IVIg mechanism of action in treating autoimmune diseases and allosensitization by accelerating pathogenic IgG antibody degradation. Trial registration number: NCT02878616.