Aerobic exercise elicits clinical adaptations in myotonic dystrophy type 1 patients independently of pathophysiological changes

BackgroundMyotonic dystrophy type 1 (DM1) is a complex life-limiting neuromuscular disorder characterized by severe skeletal muscle atrophy, weakness, and cardiorespiratory defects. Exercised DM1 mice exhibit numerous physiological benefits that are underpinned by reduced CUG foci and improved alternative splicing. However, the efficacy of physical activity in patients is unknown.MethodsEleven genetically diagnosed DM1 patients were recruited to examine the extent to which 12 weeks of cycling can recuperate clinical and physiological metrics. Furthermore, we studied the underlying molecular mechanisms through which exercise elicits benefits in skeletal muscle of DM1 patients.RESULTSDM1 was associated with impaired muscle function, fitness, and lung capacity. Cycling evoked several clinical, physical, and metabolic advantages in DM1 patients. We highlight that exercise-induced molecular and cellular alterations in patients do not conform with previously published data in murine models and propose a significant role of mitochondrial function in DM1 pathology. Finally, we discovered a subset of small nucleolar RNAs (snoRNAs) that correlated to indicators of disease severity.ConclusionWith no available cures, our data support the efficacy of exercise as a primary intervention to partially mitigate the clinical progression of DM1. Additionally, we provide evidence for the involvement of snoRNAs and other noncoding RNAs in DM1 pathophysiology.Trial registrationThis trial was approved by the HiREB committee (no. 7901) and registered under ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT04187482","term_id":"NCT04187482"}}NCT04187482).FundingNeil and Leanne Petroff. Canadian Institutes of Health Research Foundation (no. 143325).     

Evaluation of 5‐Year Risk of Cardiovascular Events in Patients after Acute Myocardial Infarction Using Synchronization of 0.1‐Hz Rhythms in Cardiovascular System

Background: Synchronization between 0.1‐Hz rhythms in cardiovascular system is deteriorated at acute myocardial infarction (AMI) leading to a disruption of natural functional couplings within the system of autonomic regulation. Objective: This study evaluates the prognostic value of autonomic regulation indices for the 5‐year risk of fatal and nonfatal cardiovascular events in patients after AMI. Methods and Results: We studied 125 patients (53 [42%] female) after AMI aged between 30 and 83 years. The period of observation was 5 years with checkpoints at the first week after AMI and after each year after AMI. We compared the prognostic value of established clinical characteristics and degree S of synchronization between 0.1‐Hz rhythms in heart rate and microcirculation for evaluation of the 5‐year risk of mortality and recurrent myocardial infarction (MI) in patients after AMI. Acute heart failure Killip 2–4 at AMI and S < 20% at the first week after AMI were identified as the most important factors for evaluation of the risk of 5‐year mortality in patients after AMI (χ²= 14.2, P = 0.003). Sensitivity and specificity of low S (<20%) at the first week after AMI were 76% and 43%, respectively. For evaluation of the 5‐year risk of recurrent MI index S had no advantage over established clinical characteristics. Conclusion: The value of S below 20% in patients with AMI is a sensitive marker of high risk of mortality during the subsequent five years. It is characterized by better prognostic value than most of established clinical characteristics.     

Lymphoangionodulary anastomosis in cancer with metastases in lymph nodes

The paper presents the research results of lymphoangionodulary anastomosis perfusion properties in breast cancer. We have carried out the detailed study of 100 axillary lymph nodes affected with metastatic breast cancer and removed them using the method of sonolipodestruction ex vivo. The results obtained in the course of the study provide a basis for a new look at the problems of lymphodynamics in metastatic damage of a lymph system.     

Medium term results of lung transplantation for end stage pulmonary sarcoidosis

BACKGROUND—Lung transplantation is an acceptedtherapeutic option for patients with end stage pulmonary sarcoidosis.However, the medium term outcome of transplantation in this patientgroup is unknown.
METHODS—This study was performed to evaluate ourexperience with lung transplantation for end stage pulmonarysarcoidosis. Between July 1988 and July 1997 12 patients (nine men)underwent lung transplantation for sarcoidosis at our institution. Tenunderwent single lung transplantation and two double lung transplantation.
RESULTS—Survival at three and five years was 70%and 56%, respectively. Three patients developed obliterativebronchiolitis at six, 18, and 45 months. One died at the time ofretransplantation. Sarcoid granulomas have recurred in the donor organin three patients. In one the development of granulomas has beenassociated with clinical deterioration, necessitatingretransplantation. Mean (SD) forced expiratory volumes in one second atthree and five years were 1.37 (0.67) l and 1.34 (0.13) l, respectively.
CONCLUSIONS—Lung transplantation is a viableoption for patients with end stage pulmonary sarcoidosis. The mediumterm results are comparable with patients undergoing lungtransplantation for other indications. Despite histological recurrenceof sarcoidosis, the risk of clinically important recurrence is low.

     

Optimal state filtering and parameter identification for linear systems

This paper presents the optimal filtering and parameter identification problem for linear stochastic systems with unknown multiplicative and additive parameters over linear observations, where unknown parameters are considered Wiener processes. The original problem is reduced to the filtering problem for an extended state vector that incorporates parameters as additional states. The obtained optimal filter for the extended state vector also serves as the optimal identifier for the unknown parameters. Performance of the designed optimal state filter and parameter identifier is verified for both stable and unstable linear uncertain systems. Copyright © 2007 John Wiley & Sons, Ltd.     

Urgent reoperation for major regional complications after removal of intracranial tumors: outcome and prognostic factors in 100 consecutive cases

Outcome of urgent reoperation for major regional complication after removal of intracranial tumor was evaluated retrospectively in 100 consecutive patients treated since 1983. Urgent reoperation was performed from 3 to 240 hours (mean 74 hours) after primary surgery for 32 meningiomas, 23 pituitary adenomas, 22 gliomas, 13 vestibular schwannomas, and 10 other intracranial neoplasms. Mean Glasgow Coma Scale (GCS) score before reoperation was 8. Brain edema was the most frequent operative finding at reoperation (31 patients), followed by extradural hematoma (25) and brain ischemia (24). Removal of various types of intracranial hematomas was the most common surgical procedure at reoperation (47 cases). Final outcome was considered favorable in 54 patients, who were discharged without major neurological deficit, and unfavorable in 46, with severe disability or vegetative state in four and death in 42. Multivariate analysis showed statistically significant association with the outcome for histological type of the tumor (p < 0.0001), clinical state at admission (p < 0.001), GCS score before urgent reoperation (p = 0.001), time interval between primary surgery and urgent reoperation (p < 0.01), and patient age (p < 0.05). Therefore, the outcome after urgent reoperation due to major regional complications after removal of intracranial tumor is determined mainly by the clinical condition of the patient and characteristics of the tumor, and less influenced by the type of complication.     

A common tattoo chemical for energy storage: henna plant-derived naphthoquinone dimer as a green and sustainable cathode material for Li-ion batteries

The burgeoning energy demands of an increasingly eco-conscious population have spurred the need for sustainable energy storage devices, and have called into question the viability of the popular lithium ion battery. A series of natural polyaromatic compounds have previously displayed the capability to bind lithium via polar oxygen-containing functional groups that act as redox centers in potential electrodes. Lawsone, a widely renowned dye molecule extracted from the henna leaf, can be dimerized to bislawsone to yield up to six carbonyl/hydroxyl groups for potential lithium coordination. The facile one-step dimerization and subsequent chemical lithiation of bislawsone minimizes synthetic steps and toxic reagents compared to existing systems. We therefore report lithiated bislawsone as a candidate to advance non-toxic and recyclable green battery materials. Bislawsone based electrodes displayed a specific capacity of up to 130 mA h g⁻¹ at 20 mA g⁻¹ currents, and voltage plateaus at 2.1–2.5 V, which are comparable to modern Li-ion battery cathodes.

The burgeoning energy demands of an increasingly eco-conscious population have spurred the need for sustainable energy storage devices, and have called into question the viability of the popular lithium ion battery.