Background and purpose
Very‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is a hereditary disorder of mitochondrial long‐chain fatty acid oxidation that has variable presentations, including ...exercise intolerance, cardiomyopathy and liver disease. The aim of this study was to describe the clinical and genetic manifestations of six patients with adult‐onset VLCADD.
Methods
In this study, the clinical, pathological and genetic findings of six adult patients (four from Iran and two from Serbia) with VLCADD and their response to treatment are described.
Results
The median (range) age of patients at first visit was 31 (27–38) years, and the median (range) age of onset was 26.5 (19–33) years. Parental consanguinity was present for four patients. Four patients had a history of rhabdomyolysis, and the recorded CK level ranged between 67 and 90 000 IU/l. Three patients had a history of exertional myalgia, and one patient had a non‐fluctuating weakness. Through next‐generation sequencing analysis, we identified six cases with variants in the ACADVL gene and a confirmed diagnosis of VLCADD. Of the total six variants identified, five were missense, and one was a novel frameshift mutation identified in two unrelated individuals. Two variants were novel, and three were previously reported. We treated the patients with a combination of L‐carnitine, Coenzyme Q10 and riboflavin. Three patients responded favorably to the treatment.
Conclusion
Adult‐onset VLCADD is a rare entity with various presentations. Patients may respond favorably to a cocktail of L‐carnitine, Coenzyme Q10, and riboflavin.
Background and purpose
The aim was to determine the electrophysiological profile of our cohort of low density lipoprotein receptor related protein 4 (LRP4) positive myasthenia gravis (MG) patients.
...Methods
A repetitive nerve stimulation (RNS) test and jitter analysis using a concentric needle electrode were performed in 17 LRP4 positive MG patients. The results were compared to 31 muscle‐specific tyrosine kinase (MuSK) positive and 28 acetylcholine receptor (AChR) positive MG patients.
Results
The RNS test was negative in almost all patients belonging to the LRP4/seronegative and LRP4/MuSK groups. It was positive most frequently in the AChR MG patients, especially those without anti‐LRP4 antibodies. The presence of anti‐LRP4 antibodies was connected to lower decrement values, whilst the independent presence of anti‐AChR or anti‐MuSK antibodies was connected to higher decrement values. Lowest jitter was recorded in patients with LRP4/seronegative MG. The highest percentage of pathological jitter analysis test results was present in MuSK and AChR MG patients. The isolate presence of anti‐LRP4 antibodies did not influence the mean consecutive difference values, whilst mean consecutive difference values were higher in the presence of anti‐AChR or anti‐MuSK antibodies.
Conclusions
Low density lipoprotein receptor related protein 4 positive patients make a distinct MG subgroup with rarely detected pathological electrophysiological test results. The lack of influence of anti‐LRP4 antibodies on the different electrophysiological parameters brings into question the pathogenic role of anti‐LRP4 antibodies in MG.
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Introduction
Generic patient reported outcome measures have had varied success in tracking QoL in myotonic dystrophy type 1 (DM1).
Aim
To analyze changes of Individualized Neuromuscular Quality of ...Life questionnaire (INQoL) scores in clinic patients with DM1 over a 6‐year period.
Method
Patients completed the INQoL at baseline and after a 6‐year period through their attendance in a neurology outpatient clinic. Severity of muscular involvement in DM1 was analyzed using the Muscular Impairment Rating Scale (MIRS).
Results
Ninety‐nine DM1 patients completed a baseline visit. Sixty‐seven of these patients were retested at an interval time. The overall INQoL score improved in our sample of patients (P<.05) as did the following subscales: myotonia (P<.05), pain (P<.05), activities (P<.01), social relationships (P<.01), and body image (P<.05). No changes were observed for the independence and emotions scales. There were no differences in mean change of INQoL scores between patients with worsened MIRS and those with no change in MIRS scale after follow‐up (P>.05).
Conclusion
Individualized Neuromuscular Quality of Life questionnaire scores improved in our cohort of DM1 patients during a 6‐year period. INQoL score did not correlate with progression of muscle weakness. This must be better understood before the selection of the instrument for use in trials to measure therapeutic benefit in DM1 patients.
Background – Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. There is a complete lack of studies that assessed quality of life (QoL) trajectory during time in DM1 ...cohorts.
Aim – To analyze changes of QoL in patients with DM1 during a 5‐year follow‐up period and to assess responsiveness of the SF‐36 questionnaire.
Patients and Method – At the baseline, this study comprised 84 DM1 patients, of whom 62 were retested after the mean period of 64.2 ± 3.9 months. Severity of muscular weakness was assessed using the Muscular Impairment Rating Scale (MIRS). Patients completed Serbian version of the SF‐36 questionnaire as a measure of health‐related QoL.
Results – After 5 years, MIRS score of our DM1 patients showed significant progression of 0.5 grade (P < 0.01). All mental subdomains, role physical, and total SF‐36 scores significantly improved after 5 years (P < 0.01). Unexpectedly, worsening of muscular weakness from mild to severe was in association with improvement of QoL.
Conclusion – QoL improved in our cohort of DM1 patients during a 5‐year period despite the progression of the disease. SF‐36 should be used with caution as a patient‐reported outcome measure in DM1 clinical trials.
In this manuscript, we establish a fixed point theorem for F -Suzuki contraction mapping over a non-triangular metric space and also give a discussion as remarks on the non-triangular metric ...structure. Moreover we introduce non-triangular metric-like space and prove a fixed point theorem for Ćirić quasi-contraction mapping therein using the property S. Examples have been cited in order to examine the validity of the underlying space and in support of our fixed point theorems.
•Probabilistic model for generation of residential energy consumption profiles.•Development of new services and applications based on synthetic energy demand data.•Simulation of effect of modified ...user behaviour or changed appliance configuration.•Quantitative evaluation of the benefits of aggregated demand optimisation.
Detailed residential energy consumption data can be used to offer advanced services and provide new business opportunities to all participants in the energy supply chain, including utilities, distributors and customers. The increasing interest in the residential consumption data is behind the roll-out of smart meters in large areas and led to intensified research efforts in new data acquisition technologies for the energy sector. This paper introduces a novel model for generation of residential energy consumption profiles based on the energy demand contribution of each household appliance and calculated by using a probabilistic approach. The model takes into consideration a wide range of household appliances and its modular structure provides a high degree of flexibility. Residential consumption data generated by the proposed model are suitable for development of new services and applications such as residential real-time pricing schemes or tools for energy demand prediction. To demonstrate the main features of the model, an individual household consumption was created and the effects of a possible change in the user behaviour and the appliance configuration presented. In order to show the flexibility offered in creation of the aggregated demand, the detailed simulation results of an energy demand management algorithm applied to an aggregated user group are used.
Background and purpose
Myasthenia gravis (MG) is an autoimmune disease but certain genetic factors predispose its development. Since susceptibility to different forms of MG is linked to a number of ...allelic variants, the aim of this study was to explore the human leukocyte antigen (HLA) profile of our patients with muscle‐specific tyrosine kinase (MuSK) MG.
Methods
Human leukocyte antigen (HLA) typing was performed in our cohort of 31 MuSK MG patients available for the study. The allele groups of DRB1* and DQB1* loci were typed with sequence‐specific oligonucleotide probes and high resolution typing for DQB1* was performed using sequence‐specific primers. HLA frequencies were compared with unrelated healthy bone marrow donors.
Results
Significant association of MuSK MG with alleles DRB1*14 odds ratio (OR) 3.8, DRB1*16 (OR 3.3) (P < 0.01) and DQB1*05 (OR 2.2) (P < 0.05) was found. In our patients the most frequent DQB1* allele was DQB1*05:02. An absolute absence of DRB1*13 in our cohort of MuSK MG patients was also found, whilst this allele was present in 25% (495/1992) of control subjects (OR 0) (P < 0.01). The HLA DRB1*16−DQB1*05 (OR 2.9) haplotype was found to be associated with MuSK MG (P < 0.05).
Conclusions
The strong association of MuSK MG with DQB1*05 alleles observed in patient series from other countries was confirmed. The novel finding in our cohort of MuSK MG patients was the absolute absence of DRB1*13 allele, which might have a protective role in the development of MuSK MG, at least in our population.
In the present paper we prove a fixed point theorem for a one parameter family of contractive self-mappings, of a complete metric space or a complete b-metric space, each member of which has a unique ...fixed point that is also the unique common fixed point of the family; the mappings may be continuous or discontinuous at the fixed point. We also prove that under the assumption of a weaker form of continuity the fixed point property for mappings satisfying the contractive conditions employed by us implies completeness of the underlying space. The characterization of completeness obtained by us not only contains Subrahmanyam?s theorem on characterization of completeness as a particular case but also extends it to b-metric spaces. Results on contractive mappings with discontinuity at the fixed point have found applications in neural networks with discontinuous activation function (e.g. Ozgur and Tas 19, 20).
The aim of this paper is to present fixed point results of Perov type contractive mappings in the framework of cone metric spaces endowed with a graphic structure. Some examples are presented to ...support the results proved herein. We also provide an example to show that our results are substantial generalization of comparable results in the existing literature. As an application of our results, we obtain fixed point results of Perov type cyclic contraction mappings in cone metric spaces.
Background and purpose
The aim of the present study was to analyze cerebrospinal fluid (CSF) levels of total tau (T‐tau), phosphorylated tau (P‐tau) and the 42‐amino‐acid form of β‐amyloid (Aβ42) in ...patients with myotonic dystrophy type 1 (DM1), and their possible correlations with cognitive and behavioral manifestations in these patients.
Methods
Lumbar puncture was performed in 74 patients with DM1 27 with the childhood/juvenile form (jDM1) and 47 with the adult form (aDM1) of the disease and 26 control subjects who were subjected to orthopedic surgery. Sandwich ELISA was used for measuring the levels of T‐tau, P‐tau and Aβ42.
Results
The CSF level of Aβ42 was at its lowest in patients with jDM1 and at its highest in controls (P < 0.05). A tendency of T‐tau and P‐tau to increase was greater in aDM1 patients than in jDM1 patients and controls (P > 0.05). In both jDM1 and aDM1 patients, significant correlations were found between Aβ42 and T‐tau (rho = 0.81 and rho = 0.67, respectively, P < 0.01), as well as between Aβ42 and P‐tau (rho = 0.87 and rho = 0.67, respectively, P < 0.01). The Aβ42/P‐tau ratio decreased with age in aDM1 patients (rho = −0.30, P < 0.05). Only the level of Aβ42 in the CSF of jDM1 patients was correlated with the size of the CTG expansion (rho = −0.53, P < 0.05). Only a few correlations were observed between levels of biomarkers and neuropsychological testing.
Conclusion
The CSF level of Aβ42 was decreased in patients with jDM1, whilst the Aβ42/P‐tau ratio was decreased in aDM1 patients. Positive correlations between Aβ42, T‐tau and P‐tau were observed in both forms of disease. Further studies with larger cohorts of DM1 patients are necessary.
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