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Amyotrophic lateral sclerosis (ALS) may result from the dysfunctions of various mechanisms such as protein accumulation, mitophagy, and biogenesis of mitochondria. The purpose of the study was to evaluate the molecular mechanisms in ALS development and the impact of swim training on these processes. In the present study, an animal model of ALS, SOD1-G93A mice, was used with the wild-type mice as controls. Mice swam five times per week for 30 min. Mice were analyzed before ALS onset (70 days old), at ALS 1 disease onset (116 days old), and at the terminal stage of the disease ALS (130 days old), and compared with the corresponding ALS untrained groups and normalized to the wild-type group. Enzyme activity and protein content were analyzed in the spinal cord homogenates. The results show autophagy disruptions causing accumulation of p62 accompanied by low PGC-1α and IGF-1 content in the spinal cord of SOD1-G93A mice. Swim training triggered a neuroprotective effect, attenuation of NF-l degradation, less accumulated p62, and lower autophagy initiation. The IGF-1 pathway induces pathophysiological adaptation to maintain energy demands through anaerobic metabolism and mitochondrial protection. KEY MESSAGES: The increased protein content of p62 in the spinal cord of SOD1-G93A mice suggests that autophagic clearance and transportation are disrupted. Swim training attenuates neurofilament light destruction in the spinal cord of SOD1-G93A mice. Swim training reducing OGDH provokes suppression of ATP-consuming anabolic pathways. Swim training induces energy metabolic changes and mitochondria protection through the IGF-1 signaling pathway., (© 2024. The Author(s).)

The aim of this paper is to analyse the mechanical properties of butt joints between S355 steel and 6061-T6 aluminium alloy, as well as their relationship to changes in the structure of the material caused by welding. The effect of the tool offset was analysed in particular. For the analysis, tensile tests were carried out using macro- and mini-specimens taken from S355/AA6061-T6 joints and base materials. In addition, the macro- and microstructure of the joints was determined, the hardness profiles in the joints were analysed, and fractographic analysis of the fractures of the specimens was carried out. Based on the results of the macro- and microstructure examinations, typical friction stir welding (FSW) joint zones were characterised. The microstructure was observed in the interface line of the materials on the root side, the negative effect of which on the quality of the joint was confirmed by digital image correlation (DIC) strain analysis during the monotonic tensile test. The highest average value of s u = 141 MPa for the entire joint was obtained for a 0.4 mm tool offset. The highest average value of s u = 185 MPa for the selected joint layer was obtained for a 0.3 mm tool offset. Fracturing of the joint in the selected layer for the tool offset values of 0.3 mm and 0.4 mm occurred in the weld nugget zone (WNZ) where the lowest hardness was recorded.

Background: It has long been suggested that reactive oxygen species (ROS) play a role in oxygen sensing via peripheral chemoreceptors, which would imply their involvement in chemoreflex activation and autonomic regulation of heart rate. We hypothesize that antioxidant affect neurogenic cardiovascular regulation through activation of chemoreflex which results in increased control of sympathetic mechanism regulating heart rhythm. Activity of xanthine oxidase (XO), which is among the major endogenous sources of ROS in the rat has been shown to increase during hypoxia promote oxidative stress. However, the mechanism of how XO inhibition affects neurogenic regulation of heart rhythm is still unclear., Aim: The study aimed to evaluate effects of allopurinol-driven inhibition of XO on autonomic heart regulation in rats exposed to hypoxia followed by hyperoxia, using heart rate variability (HRV) analysis., Material and Methods: 16 conscious male Wistar rats (350 g): control-untreated (N = 8) and pretreated with Allopurinol-XO inhibitor (5 mg/kg, followed by 50 mg/kg), administered intraperitoneally (N = 8), were exposed to controlled hypobaric hypoxia (1h) in order to activate chemoreflex. The treatment was followed by 1h hyperoxia (chemoreflex suppression). Time-series of 1024 RR-intervals were extracted from 4kHz ECG recording for heart rate variability (HRV) analysis in order to calculate the following time-domain parameters: mean RR interval (RRi), SDNN (standard deviation of all normal NN intervals), rMSSD (square root of the mean of the squares of differences between adjacent NN intervals), frequency-domain parameters (FFT method): TSP (total spectral power) as well as low and high frequency band powers (LF and HF). At the end of experiment we used rat plasma to evaluate enzymatic activity of XO and markers of oxidative stress: protein carbonyl group and 8-isoprostane concentrations. Enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measures in erythrocyte lysates., Results: Allopurinol reduced oxidative stress which was the result of hypoxia/hyperoxia, as shown by decreased 8-isoprostane plasma concentration. XO inhibition did not markedly influence HRV parameters in standard normoxia. However, during hypoxia, as well as hyperoxia, allopurinol administration resulted in a significant increase of autonomic control upon the heart as shown by increased SDNN and TSP, with an increased vagal contribution (increased rMSSD and HF), whereas sympathovagal indexes (LF/HF, SDNN/rMSSD) remained unchanged., Conclusions: Observed regulatory effects of XO inhibition did not confirm preliminary hypothesis which suggested that an antioxidant such as allopurinol might activate chemoreflex resulting in augmented sympathetic discharge to the heart. The HRV regulatory profile of XO inhibition observed during hypoxia as well as post-hypoxic hyperoxia corresponds to reported reduced risk of sudden cardiovascular events. Therefore our data provide a new argument for therapeutical use of allopurinol in hypoxic conditions.

Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles in intact cells with the use of microscopic techniques reveals a new set of different junctions and contact sites between them that contribute to the control and regulation of various cellular processes, such as calcium and lipid exchange or structural reorganization of the mitochondrial network. In recent years, many studies focused their attention on the structure and function of contacts between mitochondria and other organelles. From these studies, findings emerged showing that these contacts are involved in various processes, such as lipid synthesis and trafficking, modulation of mitochondrial morphology, endoplasmic reticulum (ER) stress, apoptosis, autophagy, inflammation and Ca 2 + handling. In this review, we focused on the physical interactions of mitochondria with the endoplasmic reticulum and plasma membrane and summarized present knowledge regarding the role of mitochondria-associated membranes in calcium homeostasis and lipid metabolism., Competing Interests: The authors declare no conflict of interest.

Background: This paper reports on aetiological factors, including mostly S. aureus infections, and antibiotic use in the pretreatment and treatment of complicating infections in patients hospitalised at the Department of Orthopaedics and Musculoskeletal Traumatology, Gdańsk Medical University, between 1995 and 2004. The analysis sought to establish a correlation, via statistical analysis, between the usage of specific antibiotic classes, with special regard to lincosamides, and S. aureus infection rates., Materials and Methods: The study population included 22,686 patients admitted for elective surgery (accounting for 86.9% to 75.1% of the sample in different years) or with acute injuries., Results: The rate of infections ranged from 2.79% to 1%, decreasing in a statistically significant manner over time. S. aureus was the dominant pathogen, accounting for 67.3% to 27.6% of the total number of bacterial strains. During the time frame of the study, the incidence of osteitis fell considerably, from 0.8% to 0.05% of the total number of patients. This was paralleled by a major increase in the use of lincosamides, mostly clindamycin. The increase in lincosamide use correlated with the decreasing incidence of S. aureus infections., Conclusions: The statistical outcome of this 10-year study has been used to develop schemes of antibiotic therapy in the Department, a necessary component of the Hospital's economic policy at the moment.A major fall in the incidence of nosocomial infections can be achieved by focussing on adequate antibiotic prophylaxis, pretreatment and appropriate treatment of acute infections.

From 1998 we performed limb-sparing surgery in 6 patients with osteosarcoma. No evidence of disease or local recurrence was noted in any of the patients after a mean follow-up period of 13 months. Age at the time of operation ranged from 8 to 14 years. Wide resection margins were achieved in all patients. The results of functional evaluation according to Enneking were excellent in 5 cases and poor in one. Bony defects created by limb-sparing procedures may be reconstructed by many methods. In growing children, limb-sparing surgery needs special consideration to avoid later limb-length discrepancy and expandable prostheses have been used to anticipate this problem.

The aim of this study was estimation of the secretory activity of macrophages isolated from granulomatotic tissue in aseptic total hip prosthesis loosening (particularly in regard to IL-6, TNF-alpha and OSM secretion). A considerable increase of IL-6 and TNF-alpha (proosteolytic cytokines) content was noted. At the same time a prominent decrease in OSM (an osteoprotective cytokine) was noted. The obtained results seem to suggest that the changed immunobiology of macrophages consisting of increase osteolytic activity and decreased osteoprotective abilities could be responsible for the loosening of hip prosthesis.

Complete acromioclavicular separation is frequent injury during practice of judo. Fourteen athletes aged 17-33 (mean 23) were treated non-operatively. All patients received cryotherapy and Velpeau bandage for two weeks, intensive rehabilitation of the shoulder followed. The patients were reviewed after mean 4.5 years (range 3-7 years). A 100-point scale designed specifically for this study, inclusive of pain, function, strength, range of motion and return to preinjury level of sports activity was used for clinical assessment. Follow-up radiographs were compared to those taken immediately after injury but no correlation with clinical results has been found. Eight results were rated excellent (90-100 points), 5 results good (80-89 points) and one result was fair (70-79 points). Short period of immobilization and early rehabilitation seems to be efficient management in highly active individuals.