Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report

Background Charcot-Marie-Tooth 1C (CMT1C) is a rare form of dominantly inherited CMT1 neuropathy caused by a mutated gene encoding lipopolysaccharide-induced tumour necrosis alpha factor (LITAF). Case presentation We report a 56-year-old patient with an atypical clinical phenotype of CMT1C, which started as progressive weakness of a single upper limb resembling acquired inflammatory neuropathy. Nerve conduction studies (NCS) and temporarily limited and partial effects of immunotherapy supported the diagnosis of inflammatory neuropathy. Significant progression of polyneuropathy, despite intensive long-lasting immunotherapy, together with repeatedly negative auxiliary investigations (CSF, MRI and antibodies) and genetic testing results finally led to the diagnosis of CMT1C neuropathy. Conclusions CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.

Partial effects in non-linear panel data models with correlated random effects

Summary Nonlinearity and heterogeneity are known to cause difficulties in estimating and interpreting partial effects. This paper provides a systematic characterization of the various partial effects in nonlinear panel data models that might be of interest to empirical researchers. The interpretation of the partial effects depends upon (i) whether the distribution of unobserved heterogeneity is treated as fixed or allowed to vary with covariates, and (ii) whether one is interested in particular covariate values or an average over such values. The characterization covers partial-effects concepts already in the literature but also includes new concepts for partial effects. A simple panel probit design highlights that the different partial effects can be quantitatively very different.

Master Regulators of Muscle Atrophy: Role of Costamere Components

The loss of muscle mass and force characterizes muscle atrophy in several different conditions, which share the expression of atrogenes and the activation of their transcriptional regulators. However, attempts to antagonize muscle atrophy development in different experimental contexts by targeting contributors to the atrogene pathway showed partial effects in most cases. Other master regulators might independently contribute to muscle atrophy, as suggested by our recent evidence about the co-requirement of the muscle-specific chaperone protein melusin to inhibit unloading muscle atrophy development. Furthermore, melusin and other muscle mass regulators, such as nNOS, belong to costameres, the macromolecular complexes that connect sarcolemma to myofibrils and to the extracellular matrix, in correspondence with specific sarcomeric sites. Costameres sense a mechanical load and transduce it both as lateral force and biochemical signals. Recent evidence further broadens this classic view, by revealing the crucial participation of costameres in a sarcolemmal “signaling hub” integrating mechanical and humoral stimuli, where mechanical signals are coupled with insulin and/or insulin-like growth factor stimulation to regulate muscle mass. Therefore, this review aims to enucleate available evidence concerning the early involvement of costamere components and additional putative master regulators in the development of major types of muscle atrophy.

Vliv postindustriální aglomerace na strukturaci občanské vybavenosti obcí v suburbánním prostoru

The article is focused on residential suburbanization, in municipalities of the hinterland of Pilsen. The article evaluates its causes and consequences of suburbanization in the area. The main goal is to evaluate whether the spatial concentration of civic amenities of municipalities changes due to suburbanization, how the distance of municipalities from the center affects the density and diversity of civic amenities. The studied region was defined by a quantitative geographical method based on daily commutes and commutes of the population for work. The aim is to analyze the defined region and field survey in individual municipalities where the occurrence of civic amenities was determined. The article evaluates the differences in the amenities of municipalities in the hinterland of Pilsen and how suburbanization affects the civic amenities of municipalities. The research found that the distance of municipalities from the center of the region has only partial effects on the species diversity and amount of civic amenities, is that the distance from the center of the defined region affects the amount and diversity only minimally. The differences were mainly demonstrated in the structure of the newly emerging development and the effects of suburbanization on the community in the municipalities.

Customer behavior impact on international tourist's travel intention due to Covid-19

Purpose: Several industries affected by the Covid-19 outbreak – one of the most affected is the tourism industry due to travel restrictions, which have resulted in an unprecedented slump in the number of international tourists. This situation has an impact on changing consumer behavior towards intention to travel. This study aims to measure the impact of Covid-19 on international tourists' consumer behavior towards crises to intention to travel overseas after the pandemic is over. Research methodology: A paper questionnaire was distributed to international tourists who have been traveling abroad (outside country of origin) at least once during the last 12 months through a nonprobability, convenience-sampling approach. A total of 350 questionnaires were analyzed using multiple regression linear. Results: The results from the regression model suggest that: (1) general impact have significant partial effects on traveling intention; (2) attitude and preference have a significant partial impact to travel intention; (3) hygiene and safety have significant partial impacts to travel intention; (4) general impact, attitude, and preference, hygiene and safety have a significant simultaneous impact to travel intention. Implications and future research issues were discussed. Limitations: This research is limited due to the limited number of respondents. Contribution: This research suggests that every country carries out promotions and increases national branding to rebuild trust to travel. Keywords: Impact, Covid-19, Customer behavior, International tourists, Travel intention, Post-pandemic

Therapeutic Applications of Cannabinoids in Cardiomyopathy and Heart Failure

A large number of cannabinoids have been discovered that could play a role in mitigating cardiac affections. However, none of them has been as widely studied as cannabidiol (CBD), most likely because, individually, the others offer only partial effects or can activate potential harmful pathways. In this regard, CBD has proven to be of great value as a cardioprotective agent since it is a potent antioxidant and anti-inflammatory molecule. Thus, we conducted a review to condensate the currently available knowledge on CBD as a therapy for different experimental models of cardiomyopathies and heart failure to detect the molecular pathways involved in cardiac protection. CBD therapy can greatly limit the production of oxygen/nitrogen reactive species, thereby limiting cellular damage, protecting mitochondria, avoiding caspase activation, and regulating ionic homeostasis. Hence, it can affect myocardial contraction by restricting the activation of inflammatory pathways and cytokine secretion, lowering tissular infiltration by immune cells, and reducing the area of infarct and fibrosis formation. These effects are mediated by the activation or inhibition of different receptors and target molecules of the endocannabinoid system. In the final part of this review, we explore the current state of CBD in clinical trials as a treatment for cardiovascular diseases and provide evidence of its potential benefits in humans.

ABHD17 enzymes regulate dynamic plasma membrane palmitoylation and N-Ras-dependent cancer growth

A subset of Ras proteins, including N-Ras, depend on a palmitoylation/depalmitoylation cycle to regulate their subcellular trafficking and oncogenicity. General lipase inhibitors such as Palmostatin M block N-Ras depalmitoylation, but lack specificity and target several enzymes displaying depalmitoylase activity. Here, we describe ABD957, a potent and selective covalent inhibitor of the ABHD17 family of depalmitoylases, and show that this compound impairs N-Ras depalmitoylation in human acute myeloid leukemia (AML) cells. ABD957 produced partial effects on N-Ras palmitoylation compared to Palmostatin M, but was much more selective across the proteome, reflecting a plasma membrane-delineated action on dynamically palmitoylated proteins. Finally, ABD957 impaired N-Ras signaling and the growth of NRAS-mutant AML cells in a manner that synergizes with MEK inhibition. Our findings uncover a surprisingly restricted role for ABHD17 enzymes in modulating the N-Ras palmitoylation cycle and suggest that ABHD17 inhibitors may have value as targeted therapies for NRAS-mutant cancers.