Force requirements of observed object lifting are encoded by the observer’s motor system: a TMS study

Several transcranial magnetic stimulation (TMS) studies have reported facilitation of the primary motor cortex (M1) during the mere observation of actions. This facilitation was shown to be highly congruent, in terms of somatotopy, with the observed action, even at the level of single muscles. With the present study, we investigated whether this muscle‐specific facilitation of the observer’s motor system reflects the degree of muscular force that is exerted in an observed action. Two separate TMS experiments are reported in which corticospinal excitability was measured in the hand area of M1 while subjects observed the lifting of objects of different weights. The type of action ‘grasping‐and‐lifting‐the‐object’ was always identical, but the grip force varied according to the object’s weight. In accordance to previous findings, excitability of M1 was shown to modulate in a muscle‐specific way, such that only the cortical representation areas in M1 that control the specific muscles used in the observed lifting action became increasingly facilitated. Moreover, muscle‐specific M1 facilitation was shown to modulate to the force requirements of the observed actions, such that M1 excitability was considerably higher when observing heavy object lifting compared with light object lifting. Overall, these results indicate that different levels of observed grip force are mirrored onto the observer’s motor system in a highly muscle‐specific manner. The measured force‐dependent modulations of corticospinal excitability in M1 are hypothesized to be functionally relevant for scaling the observed grip force in the observer’s own motor system. In turn, this mechanism may contribute, at least partly, to the observer’s ability to infer the weight of the lifted object.     

Suitability of differently formulated dry powder Newcastle disease vaccines for mass vaccination of poultry

Dry powders containing a live-attenuated Newcastle disease vaccine (LZ58 strain) and intended for mass vaccination of poultry were prepared by spray drying using mannitol in combination with trehalose or inositol, polyvinylpyrrolidone (PVP) and/or bovine serum albumin (BSA) as stabilizers. These powders were evaluated for vaccine stabilizing capacity during production and storage (at 6 °C and 25 °C), moisture content, hygroscopicity and dry powder dispersibility. A mixture design, varying the ratio of mannitol, inositol and BSA, was used to select the stabilizer combination which resulted in the desired powder properties (i.e. good vaccine stability during production and storage, low moisture content and hygroscopicity and good dry dispersibility). Inositol-containing powders had the same vaccine stabilizing capacity as trehalose powders, but were less hygroscopic. Incorporation of BSA enhanced the vaccine stability in the powders compared to PVP-containing formulations. However, increasing the BSA concentration increased the hygroscopicity and reduced the dry dispersibility of the powder. No valid mathematical model could be calculated for vaccine stability during production or storage, but the individual experiments indicated that a formulation combining mannitol, inositol and BSA in a ratio of 73.3:13.3:13.3 (wt/wt) resulted in the lowest vaccine titre loss during production (1.6-2.0 log(10) 50% egg infectious dose (EID(50)) and storage at 6 °C (max. 0.8 log(10) EID(50) after 6 months) in combination with a low moisture content (1.1-1.4%), low hygroscopicity (1.9-2.1% water uptake at 60% relative humidity) and good dry dispersibility properties.     

Interaction of sound and sight during action perception: Evidence for shared modality-dependent action representations

Seeing or hearing manual actions activates the mirror neuron system, i.e., specialized neurons within motor areas which fire not only when an action is performed but also when it is passively perceived. Although it has been shown that mirror neurons respond to either action-specific vision or sound, it remains a topic of debate whether and how vision and sound interact during action perception.Here we used transcranial magnetic stimulation to explore multimodal interactions in the human motor system, namely at the level of the primary motor cortex (M1). Corticomotor excitability in M1 was measured while subjects perceived unimodal visual (V), unimodal auditory (A), or multimodal (V + A) stimuli of a simple hand action. In addition, incongruent multimodal stimuli were included, in which incongruent vision or sound was presented simultaneously with the auditory or visual action stimulus. A selective response increase was observed to the congruent multimodal stimulus as compared to the unimodal and incongruent multimodal stimuli.These findings speak in favour of ‘shared’ action representations in the human motor system that are evoked in a ‘modality-dependent’ way, i.e., they are elicited most robustly by the simultaneous presentation of congruent auditory and visual stimuli. Multimodality in the perception of hand movements bears functional similarities to speech perception, suggesting that multimodal convergence is a generic feature of the mirror system which applies to action perception in general.     

Proprioceptive sensibility in the elderly: degeneration, functional consequences and plastic-adaptive processes

As the percentage of individuals over the age of 60 years continues to rise, determining the extent and functional significance of age-related declines in sensorimotor performance is of increasing importance. This review examines the specific contribution of proprioceptive feedback to sensorimotor performance in older adults. First, a global perspective of proprioceptive acuity is provided assimilating information from studies where only one of several aspects of proprioceptive function (e.g. sense of position, motion or dynamic position) was quantified, and/or a single joint or limb segment tested. Second, the consequences of proprioceptive deficits are established with particular emphasis placed on postural control. Lastly, the potential for plastic changes in the aging proprioceptive system is highlighted, including studies which relate physical activity to enhanced proprioceptive abilities in older adults. Overall, this review provides a foundation for future studies regarding the proprioceptive feedback abilities of elderly individuals. Such studies may lead to greater advances in the treatment and prevention of the sensorimotor deficits typically associated with the aging process.     

Murine muscle cell models for Pompe disease and their use in studying therapeutic approaches

Lysosomes filled with glycogen are a major pathologic feature of Pompe disease, a fatal myopathy and cardiomyopathy caused by a deficiency of the glycogen-degrading lysosomal enzyme, acid α-glucosidase (GAA). To facilitate studies germane to this genetic disorder, we developed two in vitro Pompe models: myotubes derived from cultured primary myoblasts isolated from Pompe (GAA KO) mice, and myotubes derived from primary myoblasts of the same genotype that had been transduced with cyclin-dependent kinase 4 (CDK4). This latter model is endowed with extended proliferative capacity. Both models showed extremely large alkalinized, glycogen-filled lysosomes as well as impaired trafficking to lysosomes. Although both Pompe tissue culture models were derived from fast muscles and were fast myosin positive, they strongly resemble slow fibers in terms of their pathologic phenotype and their response to therapy with recombinant human GAA (rhGAA). Autophagic buildup, a hallmark of Pompe disease in fast muscle fibers, was absent, but basal autophagy was functional. To evaluate substrate deprivation as a strategy to prevent the accumulation of lysosomal glycogen, we knocked down Atg7, a gene essential for autophagosome formation, via siRNA, but we observed no effect on the extent of glycogen accumulation, thus confirming our recent observation in autophagy-deficient Pompe mice [N. Raben, V. Hill, L. Shea, S. Takikita, R. Baum, N. Mizushima, E. Ralston, P. Plotz, Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease, Hum. Mol. Genet. 17 (2008) 3897–3908] that macroautophagy is not the major route of glycogen transport to lysosomes. The in vitro Pompe models should be useful in addressing fundamental questions regarding the pathway of glycogen to the lysosomes and testing panels of small molecules that could affect glycogen biosynthesis or speed delivery of the replacement enzyme to affected lysosomes.     

Choosing event‐driven and daily HIV pre‐exposure prophylaxis – data from two European PrEP demonstration projects among men who have sex with men

IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.     

The prevalence and characteristics of migraine among the Belgian working population

INTRODUCTION: Migraine is a very common disease. For the first time in Belgium, a study has been set up to assess some characteristics of the migraine problem like occurrence, frequency, duration, in a convenience sample of employees. METHODS AND STUDY POPULATION: A total of 1660 persons participated in the study. Employees completed a short international validated self-administered questionnaire (ID-Migraine Screener) in which migraine-related characteristics have been assessed. RESULTS AND DISCUSSION: Lifetime prevalence of migraine in this study was 20.2% (95% CI: 18.3-22.2%), was significantly higher for women than for men and was the highest in the age group 35-44 years. On average 10.6 lost working days due to migraine were reported per absentee and per year, or per migraineur on average 2.3 days, and per employee 0.4 days. Migraine is estimated to account for about 1,154,336 lost working days each year in Flanders and Brussels. However underreporting of symptoms, attacks and sick leave days was estimated at about 50%, depending on the time frame. Sixty-nine percent of the migraine sufferers use medication regularly. Only minor differences have been detected in migraine prevalence according to the recorded occupational risks. Finally, the limitations of the study are discussed.     

Stenting for coarctation of the aorta precipitating migraine with aura

The case of a 16-year-old girl with hypertension and coarctation of the aorta is presented. She underwent endovascular balloon dilation and stenting of the coarctation. Two days after this uncomplicated procedure, she started suffering from migraine with aura. Initially, the diagnosis of transient ischemic attacks was briefly considered, but extensive further assessment revealed no abnormalities. It is known that endovascular procedures, such as cerebral angiography or embolization of an intracranial vascular malformation, can induce migraine. To our knowledge, this is the first report of migraine with aura precipitated by an extracranial endovascular procedure: stenting for coarctation of the aorta. Series on both short-term results and long-term outcome of endovascular management of aortic coarctation have never reported migraine as a complication. Although the mechanism responsible for the onset of migraine in our patient remains unclear, it is conceivable that there was a relative intracranial hypertension before and a relative hypotension leading to hypoperfusion after dilation of the aorta. This acute disturbance of the cerebral hemodynamic balance may have set off the neurovascular mechanism leading to migraine attacks with aura.