Notes

Bloodstream lipids and anthropometric variables inside balanced subject matter practicing pilates or weight lifting within pleasurable. Precisely what things: type or perhaps intensity of exercise?
α-synuclein (α-syn) aggregation contributes to the progression of multiple neurodegenerative diseases. We recently found that the isoform b of the co-chaperone DNAJB6 is a strong suppressor of α-syn aggregation in vivo and in vitro. However, nothing is known about the role of the endogenous isoform b of DNAJB6 (DNAJB6b) in health and disease, due to lack of specific antibodies.

Here we generated a novel anti-DNAJB6b antibody to analyze the localization and expression of this isoform in cells, in tissue and in clinical material.

To address this we used immunocytochemistry, immunohistochemistry, as well as a novel quantitative DNAJB6 specific ELISA method.

The endogenous protein is mainly expressed in the cytoplasm and in neurites in vitro, where it is found more in dendrites than in axons. We further verified in vivo that DNAJB6b is expressed in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), which is a neuronal subpopulation highly sensitive to α-syn aggregation, that degenerate to a large extend in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). When we analyzed the expression levels of DNAJB6b in brain material from PD and MSA patients, we found a downregulation of DNAJB6b by use of ELISA based quantification. Interestingly, this was also true when analyzing tissue from patients with progressive supranuclear palsy, a taupathic atypical parkinsonian disorder. However, the total level of DNAJB6 was upregulated in these three diseases, which may indicate an upregulation of the other major isoform of DNAJB6, DNAJB6a.

This study shows that DNAJB6b is downregulated in several different neurodegenerative diseases, which makes it an interesting target to further investigate in relation to amyloid protein aggregation and disease progression.
This study shows that DNAJB6b is downregulated in several different neurodegenerative diseases, which makes it an interesting target to further investigate in relation to amyloid protein aggregation and disease progression.
Muscle MRI protocols have been developed to assess muscle involvement in a wide variety of muscular dystrophies. Different muscular dystrophies can involve muscle groups in characteristic patterns. These patterns can be identified in muscle MRI in the form of fatty infiltration.

This study was conducted to add the existing knowledge of muscle MRI in GNE myopathy and evaluate the correlation of muscular involvement with different gene mutations.

The MRI scans of the 18 GNE patients were analyzed retrospectively. Cluster analysis was done for grouping the muscles and patients.

The four muscles with the highest fat infiltration were adductor magnus, tibialis anterior, semitendinosus, and semimembranosus. Furthermore, three clusters of muscle involvement were found, including cluster 1, typical muscle involvement indicating muscles with the highest infiltration extensor digitorum longus, gracilis, biceps femoris, soleus, gastrocnemius medial, adductor longus, tibialis anterior, adductor magnus, semimembranosus, semitendinosus; cluster 2, less typical muscle involvement indicating muscles with intermediate fat infiltration, peroneus longus, gastrocnemius lateral, and minimal fat infiltration in most of the patients, i.e., tibialis posterior; and cluster 3, atypical muscle involvement with low-fat infiltration rectus femoris, sartorius, vastus intermedius, vastus medialis, and vastus lateralis.

This study found three clusters of muscle involvement and three groups of patients among GNE patients. Hamstring muscles and the anterior compartment of the lower leg were the muscles with the highest fat infiltration. Moreover, a weak genotype-muscle MRI association was found in which tibialis posterior was more involved in patients with the most frequent mutation, i.e., C.2228T > C (p.M743T) mutation; however, this finding may be related to longer disease duration.
 C (p.M743T) mutation; however, this finding may be related to longer disease duration.
For patients with rare diseases such as Duchenne and Becker muscular dystrophy (DMD/BMD), access to their health data is key to being able to advocate for themselves and be in control of their care. Since 2018, the DMD/BMD patient community has been committed to making DMD/BMD-related data FAIR, ie, Findable, Accessible, Interoperable, and Reusable. On March 3, 2021, the second international meeting on FAIR data sharing for DMD/BMD was held virtually.

The aim of this meeting report is to summarize the presentations and discussions of the meeting.

During this meeting, the progress of FAIRification efforts since the first international meeting in 2019, new developments, stakeholder perspectives, and experiences from implementing FAIR data principles in practice were presented and discussed.

Over 120 attendees representing various stakeholder groups (ie, patient organizations, clinicians, clinical and academic researchers, pharmaceutical companies, regulators, and EU organizations) from 22 countries participated in the meeting. This meeting report summarizes the presentations and discussions from the meeting, provides an overview of the key lessons learned since the first meeting, and outlines the next steps.

Patient organizations are key drivers of the FAIRification process in practice and dialogue with stakeholders is critical to success.
Patient organizations are key drivers of the FAIRification process in practice and dialogue with stakeholders is critical to success.
Physical activity (PA) in patients with myasthenia gravis (MG) is considered safe and beneficial, and an active lifestyle is required to obtain the health benefits of exercise. However, as the disease leads to physical impairments an insight into the overall PA habits in this patient population is relevant but lacking.

To measure habitual physical activity in a Danish cohort of patients with MG measured by accelerometer and questionnaire, and to determine relevant predictors for PA intensities.

Habitual physical activity was assessed by; 1) the accelerometer Acti Graph in a cohort of patients recruited from our neuromuscular clinic, 2) the International Physical Activity Questionnaire (IPAQ) in a web-based survey. PA levels were compared to international recommendations. Predictors for PA (age, sex, body mass index, disease severity and duration) were included in the regression analyses.

Habitual physical activity was measured by accelerometer for 7 days in 69 patients and by questionnaire in 691 patients. Measured by the accelerometer, 46%of the patients did not meet the international recommendations for PA at moderate/vigorous intensity and 57%were below the recommendations for steps per day. Measured by the IPAQ, 48%did not meet the recommendations. Disease severity and age were predictors for PA intensities.

This study found that around half of the included patients did not meet the recommendations for PA. This is a concern, as it increases the risk of life-style related diseases. Disease severity and age may be taking into consideration when counseling the patients about PA.
This study found that around half of the included patients did not meet the recommendations for PA. This is a concern, as it increases the risk of life-style related diseases. Disease severity and age may be taking into consideration when counseling the patients about PA.Adult skeletal muscle is a relatively stable tissue, as the multinucleated muscle fibres contain post-mitotic myonuclei. During early postnatal life, muscle growth occurs by the addition of skeletal muscle stem cells (satellite cells) or their progeny to growing muscle fibres. In Duchenne muscular dystrophy, which we shall use as an example of muscular dystrophies, the muscle fibres lack dystrophin and undergo necrosis. Satellite-cell mediated regeneration occurs, to repair and replace the necrotic muscle fibres, but as the regenerated muscle fibres still lack dystrophin, they undergo further cycles of degeneration and regeneration.AAV gene therapy is a promising approach for treating Duchenne muscular dystrophy. But for a single dose of, for example, AAV coding for dystrophin, to be effective, the treated myonuclei must persist, produce sufficient dystrophin and a sufficient number of nuclei must be targeted. This latter point is crucial as AAV vector remains episomal and does not replicate in dividing cells. Here, we describe and compare the growth of skeletal muscle in rodents and in humans and discuss the evidence that myofibre necrosis and regeneration leads to the loss of viral genomes within skeletal muscle. In addition, muscle growth is expected to lead to the dilution of the transduced nuclei especially in case of very early intervention, but it is not clear if growth could result in insufficient dystrophin to prevent muscle fibre breakdown. This should be the focus of future studies.BackgroundIn myasthenia gravis, impaired postsynaptic sensitivity to acetylcholine results in failure of neuromuscular transmission and fatiguing muscle weakness.ObjectiveDevelop an ex vivo muscle contraction assay to test cannabinoids and other substances that might act on the myasthenic neuromuscular junction to restore control of the muscle.MethodsTubocurarine was added to an ex vivo, mouse phrenic nerve-hemidiaphragm muscle preparation to reduce acetylcholine sensitivity. This produced a myasthenia-like decrement in twitch force during a train of 10 nerve impulses (3 / sec). Endplate potential (EPP) recordings were used to confirm and extend the findings.ResultsSurprisingly, addition to the bath of dimethylsulphoxide (DMSO), at concentrations as low as 0.1%(v/v), partially reversed the decrement in nerve-evoked force. Intracellular electrophysiology, conducted in the presence of tubocurarine, showed that DMSO increased the amplitudes of both the spontaneous miniature EPP (MEPP) and the (nerve-evoked) EPP. In the absence of tubocurarine (synaptic potentials at physiological levels), an adaptive fall in quantal content negated the DMSO-induced rise in EPP amplitude. The effects of cannabinoid receptor agonists (solubilized with DMSO) in the contraction assay do not support their further exploration as useful therapeutic agents for myasthenia gravis. CP 55,940 (a dual agonist for cannabinoid receptor types 1 and 2) reversed the beneficial effects of DMSO.ConclusionsWe demonstrate a powerful effect of DMSO upon quantal amplitude that might mislead pharmacological studies of synaptic function wherever DMSO is used as a drug vehicle. Our results also show that compounds targeting impaired neuromuscular transmission should be tested under myasthenic-like conditions, so as to avoid confounding effects of synaptic homeostasis.Some patients with Oculopharyngeal Muscular Dystrophy (OPMD) develop frontotemporal dementia (FTD). The prevalence and clinical correlates of behavioural impairment, including FTD, is unknown in OPMD.24 OPMD patients and their proxies completed a questionnaire concerning behavioural impairment (ALS-FTD-Q). We examined proportions with mild or severe behavioural changes, according to validated cut-off proxy scores. We examined correlations with the Hospital Anxiety and Depression Scale (HADS), the Short Form Health Survey (SF-36), motor symptoms, genotype and disease duration.In this small patient sample, behavioural impairment was present in 29%of OPMD patients; in 17%the severity of symptoms was compatible with bvFTD. selleck products Correlations were small to medium.
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