Accumulating data suggest that the brain undergoes various changes during aging. Among them are loss of both white and gray matter, neurons and synapses degeneration, as well as oxidative, inflammatory, and biochemical changes. The above-mentioned age-related features are closely related to autophagy and mitochondria. Therefore, we aimed to reveal the most peculiar morphological features of brain nervous tissue and to characterize the expression of autophagy and mitochondrial immunohistochemical biomarkers in neurons of different human brain zones during aging. Counting the number of neurons as well as Microtubule-associated proteins 1A/1B light chain 3B (LC3B), Heat shock protein 70 (HSP70), Lysosome-associated membrane protein type 2A (LAMP2A), Alpha subunit of ATP synthase (ATP5A), and Parkinson disease protein 7 (DJ1) immunohistochemical staining were performed on FFPE samples of human prefrontal cortex, corpus striatum, and hippocampus obtained from autopsy. Statistical analysis revealed a loss of neurons in the studied elderly group in comparison to the young group. When the expression of macroautophagy (LC3B), chaperon-mediated autophagy (HSP70, LAMP2A), and mitochondrial respiratory chain complex V (ATP5A) markers for the young and elderly groups were compared, the latter was found to have a significantly higher rate of optical density, whilst there was no significance in DJ1 expression. These findings, while preliminary, suggest that both autophagy and mitochondria are involved in neuronal maintenance during aging and could indicate their potential role in adaptive mechanisms that occur in aging.
Objective: Amyotrophic lateral sclerosis is a neurodegenerative disease with high rates of disability and mortality. Non-invasive ventilation (NIV) is an effective method of treating patients, increasing life expectancy, but currently, predictors available to determine the best outcome of therapy in this category of patients are unknown. This systematic review aimed to determine the impact of prognostic factors on benefits from NIV application compared with non-NIV tools of treatment (invasive ventilation and standard care) in case of survival of ALS patients. Method: We systematically sought relevant longitudinal cohort and case-control studies published in PubMed, CINAHL/EMBASE, Cochrane library, and Scopus. Results: We included seven prospective studies, published in 2010–2020, in the analysis. According to the evidence base available to date, NIV favors survival compared to non-NIV in patients with bulbar onset ALS. We obtained conflicting data on the significance of spinal onset and bulbar function. Survival depending on patient age, and also for spinal, cervical, and flail limb phenotypes during NIV therapy has not been sufficiently studied and needs further investigation. Conclusions: The studies analyzed in this review allow us to state with confidence that NIV is effective in bulbar onset ALS, taking into account recommendations for duration of ventilation and the use of the full range of symptomatic therapy, including mechanically assisted coughing. The effectiveness of NIV on severe bulbar symptoms requires further research.
Supporting of the functional pool of neurons during age-related brain involution is closely related to chaperone-mediated autophagy, the main function of which is to provide cellular proteostasis and utilize neurotoxic proteins. Impairment of this type of autophagy underlies the pathogenesis of many age-associated neurodegenerative diseases. In this aspect, it seems relevant to study the relationship between key markers of chaperone-mediated autophagy and their relative contribution to aging and neurodegeneration in order to determine pharmaceutical targets. The aim of the study was to determine the levels of expression of markers of chaperone-mediated autophagy - heat shock protein 70 (HSP70) and lysosome-associated membrane protein type 2A (LAMP2) in neurons of various areas of the human brain during aging. The study was performed on autopsy material of patients whose causes of death were not associated with neurological diseases. Preparations of the cortex of the precentral gyrus, striatum and hippocampus were studied in the group of cases of young age (35-45 years, n=5) and senile age (>75 years, n=10). Immunohistochemical staining was performed using primary antibodies to HSP70 and LAMP2. Optical density was assessed in the perikaryon of 150 large neurons in layer V of the cortex of the precentral gyrus, striatum, and pyramidal layer of the hippocampus. The results of the study demonstrated an increase in the expression of both HSP70 and LAMP2A in brain preparations from cases of senile age. The higher values of the optical density of HSP70 compared to LAMP2A in brain preparations from senile cases were probably due to dissociation between the stage of substrate binding and the stage of its translocation. It can be assumed that the binding of nonfunctioning proteins to HSP70 and cochaperones occurs faster than their movement into the lumen of lysosomes via LAMP2A. The results obtained suggest that the increasing of levels of markers of chaperone-mediated autophagy may be of a compensatory-adaptive nature and ensure the survival of neurons under conditions of chronic stress during physiological aging.
INTRODUCTION: Malignant peripheral nerve sheath tumor (MPNST) occurs in young and middle-aged people, more frequently in those with the genetic disease known as neurofibromatosis type 1 (NF1). Approximately, 50% of people with MPNST have NF1 and 13% of people with NF1 will get MPNST during their lifetime. CASE REPORT: A 30-year-old patient after surgery for MPNST of the right hip in 2013 was observed. In 2017, a relapse was detected, and combined treatment was performed, including surgical excision of the relapse and postoperative distance radiotherapy with a total focal dose of 66 Gy. In 2018, MPNST of the left femoral nerve was diagnosed, and the tumor was excised. In 2020, a chest X-ray diagnosed a single focus of localized opacity in the anterior mediastinum, adjacent to the right lung. Computed tomography (CT) was performed to further verify the neoplasm, which revealed a single hypodense focus in the anterior mediastinum, adjacent to the right lung. According to histological examination of a tumor biopsy obtained by transthoracic ultrasound-guided biopsy, MPNST was verified. Magnetic resonance imaging (MRI) with intravenous contrast enhancement, including real-time MRI, was performed to assess the invasion of the mass into soft tissues and vessels and to plan surgical treatment. The following surgeries were done: right thoracotomy, removal of a neoplasm of the anterior mediastinum with resection of the upper lobe of the right lung, and marginal resections of the lower lobe of the right lung. This case demonstrates a rare localization and non-standard instrumental diagnosis of mediastinal MPNST. Apart from CT scanning, the patient underwent MRI of the thoracic organs. MRI allows assessing the invasion of the neoplasm into the surrounding tissues. This cannot always be achieved by CT scans, including those with contrast enhancement. Invasion is an important component in the planning of further surgical treatment tactics. CONCLUSIONS: MPNST is a tumor with an aggressive course and a poor prognosis due to resistance to therapy. This clinical case demonstrates a rare localized MPNST with a recurrent course and metastases to the lungs. The current radiological methods, such as CT and MRI, may be used effectively both for diagnosing MPNST and determining the appropriate surgical access to the lesion and the extent of surgery.
INTRODUCTION: Nowadays there are a lot of different rating and prognostic scales that allow to objectify the patient’s condition. OBJECTIVE: To identify the awareness of the staff of intensive care units in different medical organizations of the Russian Federation regarding assessment tools, to analyze the preferences of using and to determine the quality of knowledges about the validity of the assessment tools used. MATERIALS AND METHODS: The authors analyzed 693 Russian-language sources published between 2018–2022 years from the following databases: Elsevier, Google Scholar, PubMed, eLIBRARY, and official site of Federation of Anesthesiologists and Reanimatologists of Russia. During the analysis the most commonly used scoring systems were extracted and included in the questionnaire to anesthesiologists-reanimatologists working in Moscow hospitals. RESULTS: According to the answers received from 120 respondents, the most frequently used scales were (American Society of Anaesthesiologists Scale (ASA) and Richmond Agitation-Sedation Scale (RASS) (95.83 and 93.33 %, respectively). Also, the authors revealed the statistically significant differences in clinical application of the scales between respondents. Specialists from Federal hospitals commonly used Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria for assessment of acute kidney failure (73.47 %). However, representatives from City hospitals used the Glasgow Outcome Scale more often in their practice (60.94 %). CONCLUSIONS: To sum it up, not all of existed scoring systems are implemented into the clinical practice of intensive care unit (ICU) specialists. The most commonly used scales revealed in the current study were anesthesiological ones. Concerning another types of scales, their usage depended on specifics of ICU department, ICU specialists’ work experience. That is why the following data in this study demonstrates the non-awareness of the anesthesiologists and reanimatologists for validation of scoring systems in Russia.