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Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity. This study addresses the critical gap in our understanding of modifiable lifestyle factors, such as physical exercise, that may mitigate retinal aging and its related pathologies. We investigated the effects of different exercise regimens-voluntary (recreational-type) and forced (high-intensity)-on the retinal health of aging Wistar rats (18-month-old), serving as a model for studying the translational potential of exercise interventions in humans. Male Wistar rats were divided into four groups: a young control (3-month-old) for baseline comparison, an aged sedentary control, an aged group engaging in voluntary exercise via a running wheel in their cage, and an aged group subjected to forced exercise on a treadmill for six sessions of 20 min each per week. After a 6-month experimental period, we assessed retinal function via electroretinography (ERG), measured retinal thickness histologically, and analyzed protein expression changes relevant to oxidative stress, inflammation, and anti-aging mechanisms. Our findings reveal that voluntary exercise positively impacts retinal function and morphology, reducing oxidative stress and inflammation markers while enhancing anti-aging protein expression. In contrast, forced exercise showed diminished benefits. These insights underscore the importance of exercise intensity and preference in preserving retinal health during aging. The study highlights the potential of recreational physical activity as a non-invasive strategy to counteract retinal aging, advocating for further research into exercise regimens as preventative therapies for age-related ocular degenerations.
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Envejecimiento , Electrorretinografía , Condicionamiento Físico Animal , Ratas Wistar , Retina , Animales , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Masculino , Envejecimiento/fisiología , Ratas , Estrés Oxidativo/fisiologíaRESUMEN
Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund's adjuvant (CFA)-induced chronic arthritis rat model and to identify new biomarkers with clinical utility. CFA was injected into the plantar surface of one hind paw and the root of the tail on day 0, and the tail root injection was repeated on day 1. Flu vaccination was performed on day 1 or 7. Paw volume was measured by plethysmometry, mechanonociceptive threshold by dynamic plantar aesthesiometry, neutrophil myeloperoxidase (MPO) activity, and vascular leakage using in vivo optical imaging throughout the 21-day experiment. Inflammatory markers were determined by Western blot and histopathology. CFA-induced swelling, an increase in MPO activity, plasma extravasation in the tibiotarsal joint. Mechanical hyperalgesia of the hind paw was observed 3 days after the injection, which gradually decreased. Co-administration of the flu vaccine on day 7 but not on day 1 resulted in significantly increased heme oxygenase 1 (HO-1) expression. The influenza vaccination appears to have a limited impact on the progression and severity of the inflammatory response and associated pain. Nevertheless, delayed vaccination could alter the disease activity, as indicated by the findings from assessments of edema and inflammatory biomarkers. HO-1 may serve as a potential marker for the severity of inflammation, particularly in the case of delayed vaccination. However, further investigation is needed to fully understand the regulation and role of HO-1, a task that falls outside the scope of the current study.
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Artritis Experimental , Gripe Humana , Ratas , Animales , Humanos , Artritis Experimental/metabolismo , Adyuvante de Freund/efectos adversos , Hiperalgesia/metabolismo , Inflamación , Vacunación , Progresión de la EnfermedadRESUMEN
PURPOSE: In the case of Hungarian folk dancers, it is crucial to maintain correct posture and promptly respond to imbalances. However, traditional dances often lack specific training to develop these skills. METHODS: In this present study, twelve dancers (8 male, 4 female, age: 21.7 ± 3.6 years) and ten non-dancers subjects forming a control group (6 male, 4 female, age: 21.6 ± 2.87 years) participated. During the measurements a 60-second long bipedal balancing test on the balance board was completed two times, and a spinning intervention was inserted in between the two sessions. The balance capabilities of the two groups were assessed through the characterization of motion on an unstable board, and the analysis of subject's center of mass and head movements. RESULTS: Dancers applied a more sophisticated and resource-intensive strategy to address the balancing task, yielding a better balancing performance in terms of balance board parameters. By preferring a solid stability in the medio-lateral direction, a greater fluctuation in the anterior-posterior direction can be observed (e.g., significantly lower SampEn values). The overall more successful performance is further evidenced by within-subject comparison since significant differences were observed mostly within the control group. Based on the results, the advanced balancing ability of the folk dancer group is more likely to be acquired through years of experience. CONCLUSION: The results indicate that additional specialized training could further enhance this ability, encouraging the reliance on poorly memorized corrective movements and reducing the risk of injury.
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The role of donor-derived tendons, also known as allografts, in anterior cruciate ligament replacement surgeries is steadily increasing. Before surgery, temporary storage and, in most cases, sterilization are essential. It is, thus, crucial to determine how these procedures alter the grafts' biomechanical properties. The purpose of this research was to analyze the effect of different sterilization methods (native, frozen, frozen + 21 kGy gamma irradiation, frozen + 21 kGy electron beam irradiation) and storage durations (0 to 4 months) on the deformation and creep of two tendon types (tibialis anterior, peroneus longus). 80 tibialis anterior and 83 peroneus longus tendons from 51 human cadavers were included. The samples were removed, placed in a radio-cryoprotectant solution, then slowly cooled, sterilized and stored at -80 °C. All groups were subject to 60 s static creep test with 250 N load. Deformation during the loading phase, creep during static loading, and the ratio of these two were evaluated. Deformation at the end of the loading phase and creep consistently exhibited significantly smaller values in the tibialis anterior compared to the peroneus longus type, as well as in electron beam-sterilized grafts as opposed to gamma beam-sterilized ones. Prolonged storage periods (within 0 to 4 months) resulted in a notable increase in these values, particularly in deformation. Based on the experimental data, the tibialis anterior tendon type and sterilization by gamma beam irradiation are better choices for anterior cruciate ligament reconstruction than the peroneus longus and sterilization by electron beam. Increased storage time affects negatively the evaluated mechanical properties.
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Lesiones del Ligamento Cruzado Anterior , Tendones , Humanos , Fenómenos Biomecánicos , Trasplante Homólogo/métodos , Tendones/trasplante , Esterilización/métodos , Aloinjertos/efectos de la radiaciónRESUMEN
Total en bloc spondylectomy (TES) effectively treats spinal tumors. The surgery requires a vertebral body replacement (VBR), for which several solutions were developed, whereas the biomechanical differences between these devices still need to be completely understood. This study aimed to compare a femur graft, a polyetheretherketone implant (PEEK-IMP-C), a titan mesh cage (MESH-C), and a polymethylmethacrylate replacement (PMMA-C) using a finite element model of the lumbar spine after a TES of L3. Several biomechanical parameters (rotational stiffness, segmental range of motion (ROM), and von Mises stress) were assessed to compare the VBRs. All models provided adequate initial stability by increasing the rotational stiffness and decreasing the ROM between L2 and L4. The PMMA-C had the highest stiffness for flexion-extension, lateral bending, and axial rotation (215%, 216%, and 170% of intact model), and it had the lowest segmental ROM in the instrumented segment (0.2°, 0.5°, and 0.7°, respectively). Maximum endplate stress was similar for PMMA-C and PEEK-IMP-C but lower for both compared to MESH-C across all loading directions. These results suggest that PMMA-C had similar or better primary spinal stability than other VBRs, which may be related to the larger contact surface and the potential to adapt to the patient's anatomy.
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Polimetil Metacrilato , Fusión Vertebral , Humanos , Análisis de Elementos Finitos , Vértebras Lumbares/cirugía , Rango del Movimiento Articular , Fenómenos Biomecánicos , Fusión Vertebral/métodosRESUMEN
Epilepsy is one of the most common neurological disorders. Therapeutic success shows high variability between patients, at least 20-30% of the cases are drug-resistant. It can highly affect the social status, interpersonal relationships, mental health and the overall quality of life of those affected.
Although several studies can be found on the psychiatric diseases associated with epilepsy, only a few researches focus on the occurrence of personality disorders accompanying the latter. The aim of this review is to help clinicians to recognize the signs of personality disorders and to investigate their connection and interaction with epilepsy in the light of current experiences.
The researches reviewed in this study confirm that personality disorders and pathological personality traits are common in certain types of epilepsy and they affect many areas of patients’ lives. These studies draw attention to the importance of a multidisciplinary approach to this neurological disorder and to provide suggestions about the available help options. Considering the high frequency of epilepsy-related pathological personality traits that can have a great impact on the therapeutic cooperation and on the patients’ quality of life, it important that the neurologist recognizes early the signs of the patient’s psychological impairment. Thus they can get involved in organizing the support of both the patient and their environment by including psychiatrists, psychologists, social and self-help associations.
As interdisciplinary studies show, epilepsy is a complex disease and besides trying to treat the seizures, it is also important to manage the patient’s psychological and social situation. Cooperation, treatment response and quality of life altogether can be significantly improved if our focus is on guiding the patient through the possibilities of assistance by seeing the complexity and the difficulties of their situation.
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Epilepsia , Trastornos Mentales , Humanos , Calidad de Vida , Trastornos de la Personalidad/complicaciones , Trastornos Mentales/diagnóstico , Epilepsia/diagnóstico , Convulsiones/diagnóstico , Salud MentalRESUMEN
This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide-protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group. Dyslipidemia, impaired endothelial function, and signs of diastolic dysfunction were evident in hypercholesterolemic rabbits, accompanied by a reduced cardiac expression of eNOS (endothelial nitric oxide synthase), PKG, and SERCA2a (sarco/endoplasmic reticulum calcium ATPase 2a). Subsequent PCE treatment improved the lipid profile and the cardiac function. Additionally, PCE administration was associated with elevated myocardial levels of eNOS, PKG, and SERCA2a, while no significant changes in the vascular status were observed. Western blot analysis further revealed hypercholesterolemia-induced increase and PCE-associated reduction in heme oxygenase-1 expression. The observed effects of anthocyanins indicate their potential as a valuable addition to the treatment regimen for atherosclerosis-associated cardiac dysfunction.
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Aterosclerosis , Cardiopatías , Lagomorpha , Prunus avium , Animales , Conejos , Antocianinas/farmacología , Antocianinas/uso terapéutico , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológicoRESUMEN
This study aimed at the relationship between antioxidant capacity, antimicrobial activity, and in vitro evaluation of the wound healing effect of the extract obtained from Echinaceae purpureae folium (EPF). This study's objective was to assess the bioactive components (total phenol and flavonoid content) and antioxidant activity of EPF extracts using the DPPH test method. The antioxidant capacity and the quantities of the compounds with antioxidant capacity were evaluated by spectrophotometric methods. Antimicrobial activity has been investigated against various pathogenic microorganisms. The minimum inhibitory concentration was determined by the microdilution method. Additionally, our work used a scratch test to examine the in vitro wound healing effects of EPF extract on NHDF cells. Statistical analysis was used to quantify the rate of migration and proliferation of fibroblast cells within the wound. Microscope pictures of fibroblast cells exposed to various EPF extract dosages were processed to estimate the width of the wound, area of the wound, and cell density inside the wound. The study proved that there was a relationship between the antioxidant, antimicrobial, and wound healing ability of EPF extracts.
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Antiinfecciosos , Echinacea , Antioxidantes/farmacología , Antioxidantes/análisis , Echinacea/química , Cicatrización de Heridas , Extractos Vegetales/química , Antiinfecciosos/farmacología , Antiinfecciosos/análisis , Hojas de la Planta/químicaRESUMEN
BACKGROUND: The prone plank test has been often used to assess the strength and endurance of trunk muscles. We aimed to develop a new measurement protocol to objectively monitor the changes in spinal curves and muscle activity simultaneously. METHODS: Eleven adolescent male basketball athletes (13-17 years) performed a one-minute plank test. Spinal curvatures (thoracic kyphosis (TK) and lumbar lordosis (LL)) were determined at each time point by optical tracking of markers placed on the spinous processes of 10 vertebrae. Eleven muscles were measured by surface electromyography to determine muscle fatigue via changes in median frequency. RESULTS: TK significantly increased (p = 0.003) from the first to the last 10 s of the plank test; changes in LL were mixed within the group. Only the rectus abdominis showed consistent and significant fatigue (p < 0.001). The increased spinal curves significantly correlated with the fatigue of biceps femoris (TK: r = -0.75, p = 0.012; LL: r = -0.71, p = 0.019) indicating a compensatory muscle activation and spinal curve changes in response to fatigue. CONCLUSION: Our protocol may support future researches that aim to objectively evaluate the prone plank test and which posture-related muscles need strengthening for the individual.
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The COVID-19 pandemic has posed a huge challenge to the world in recent years. The development of vaccines that are as effective as possible and accessible to society offers a promising alternative for addressing the problems caused by this situation as soon as possible and to restore the pre-epidemic system. The present study investigated the preferences of residents in Hungary's second-largest city (Debrecen) for the COVID-19 vaccine. To achieve this aim, a discrete choice experiment was conducted with 1011 participants, and the vaccine characteristics included in the design of the experiment were determined by qualitative methods and a pilot survey: (1) country of origin; (2) efficiency; (3) side effect; and (4) duration of protection. During the data collection at three vaccination sites, respondents were asked to choose between three vaccine alternatives and one "no choice" option in eight decision situations. Discrete choice model estimations were performed using a random parameter logit (RPL) specification with the final model extended to include a latent variable measuring pandemic awareness. The results showed that the vaccine with a Chinese country of origin is the least preferred among the respondents, while the Hungarian and the European vaccines are the most preferred. Furthermore, the increase in the vaccine efficiency level increased the respondents' sense of utility for the vaccine; the short-term side effect was preferred to the long-term one; and the increase in the duration of protection provided by the vaccine increased the respondents' sense of utility for the vaccine. Based on the parameter estimated for the latent variable, it can be concluded that as the level of pandemic awareness (which is more positive among people with chronic diseases and less important among health workers) increases, the choice of a vaccine option becomes more preferred among respondents compared to the "no choice". The results of our investigation could contribute towards increasing compliance in the case of the vaccination-rejecting population, not only for COVID-19, but for any kind of vaccination procedure.
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COVID-19 , Vacunas , Humanos , Vacunas contra la COVID-19/uso terapéutico , Pandemias/prevención & control , Hungría , Conducta de Elección , COVID-19/epidemiología , COVID-19/prevención & control , VacunaciónRESUMEN
We examined the effects of side-dominance on the laterality of standing stability using ground reaction force, motion capture (MoCap), and EMG data in healthy young adults. We recruited participants with strong right (n = 15) and left (n = 9) hand and leg dominance (side-dominance). They stood on one or two legs on a pair of synchronized force platforms for 50 s with 60 s rest between three randomized stance trials. In addition to 23 CoP-related variables, we also computed six MoCap variables representing each lower-limb joint motion time series. Moreover, 39 time- and frequency-domain features of EMG data from five muscles in three muscle groups were analyzed. Data from the multitude of biosignals converged and revealed concordant patterns: no differences occurred between left- and right-side dominant participants in kinetic, kinematic, or EMG outcomes during bipedal stance. Regarding single leg stance, larger knee but lower ankle joint kinematic values appeared in left vs right-sided participants during non-dominant stance. Left-vs right-sided participants also had lower medial gastrocnemius EMG activation during non-dominant stance. While right-side dominant participants always produced larger values for kinematic data of ankle joint and medial gastrocnemius EMG activation during non-dominant vs dominant unilateral stance, this pattern was the opposite for left-sided participants, showing larger values when standing on their dominant vs non-dominant leg, i.e., participants had a more stable balance when standing on their right leg. Our results suggest that side-dominance affects biomechanical and neuromuscular control strategies during unilateral standing.
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Patients undergoing unilateral orthopedic or neurological rehabilitation have different levels of impairments in the right- or left-dominant hand. However, how handedness and the complexity of the motor task affect motor skill acquisition and its interlimb transfer remains unknown. In the present study, participants performed finger key presses on a numeric keypad at 4 levels of sequence complexities with each hand in a randomized order. Furthermore, they also performed motor sequence practice with the dominant hand to determine its effect on accuracy, reaction time, and movement time. The NASA-TLX at the end of each block of both testing and practice was used to confirm participants' mental workload related to sequence complexity. Both right- and left-handed participants performed the motor sequence task with faster RT when using their right hand. Although participants had increasing RT with increasing sequence complexity, this association was unrelated to handedness. Motor sequence practice produced motor skill acquisition and interlimb transfer indicated by a decreased RT, however, these changes were independent of handedness. Higher sequence complexity was still associated with longer RT after the practice, moreover, both right- and left-handed participants' RT increased with the same magnitude with the increase in sequence complexity. Similar behavioral pattern was observed in MT as in RT. Overall, our RT results may indicate left-hemisphere specialization for motor sequencing tasks, however, neuroimaging studies are needed to support these findings. On the other hand, handedness did not affect motor skill acquisition by the dominant hand or interlimb transfer to the non-dominant hand regardless of task complexity level.
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Lateralidad Funcional , Destreza Motora , Humanos , Desempeño Psicomotor , Movimiento , Tiempo de Reacción , ManoRESUMEN
The objective of the present pilot study was to determine the force required to break (a) intact canine tibiae, (b) tibiae following the osteotomy of the tibial tuberosity and (c) tibiae following Tibial Tuberosity Advancement- (TTA-) rapid surgery. Six pairs of tibiae of dogs between 15 and 35 kg body weight were used in a cadaver study. Three groups were created with four tibiae in each group; intact (Group 1), osteotomy of the tibial tuberosity and tibial crest (Group 2) and TTA-rapid (Group 3). The tibiae were put under static axial compressive load, applied until failure. The force required to break the tibiae was termed maximal force (F max). The mean of F max was 8193.25 ± 2082.84 N in Group 1, 6868.58 ± 1950.44 N in Group 2 and 7169.71 ± 4450.39 N in Group 3. The sample size was small for a statistical analysis but as a preliminary result, we have determined the force (F max) required to break canine tibiae. Furthermore, we hypothesise that osteotomies result in weakening of the tibial structure.
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BACKGROUND: The use of tendon allografts for orthopedic repair has gained wide acceptance in recent years, most notably in anterior cruciate tendon reconstruction. Multiple studies support the use of tendon allografts and the benefits of its use are well accepted and understood. One of the important criteria of the use of tendon allografts is statistically similar histological and biomechanical properties to autographs. The aim of this systematic literature review is to investigate and categorize existing clamps used in the determination of the biomechanical properties of tendons such as maximum load, maximum strength, modulus of elasticity, ultimate strain, and stiffness. A variety of clamps for use during the endurance test of tendons were categorized according to the temperature used during the measurement. The clamps are divided into three groups: room temperature, cooled and heated clamps. The second goal of our review is to overview of clamps on the following aspects: name of clamp, author and date, type of clamps, type of endurance test (static or dynamic), type preloading (dynamic or static), type of tendon and measured and calculated parameters, and summarize in Table 3, as a comprehensive catalogue. METHODS: This systematic review was carried out in keeping with the PRISMA 2020 E&E and the PRISMA-S guidelines and checklists. A search was conducted for publications dating between 1991 and February 28th 2022 through three electronic databases (Web of Science, Scopus, and PubMed). We used Critical Appraisal Skills Program checklist to check the quality of included articles. RESULTS: The database search and additional sources resulted in 1725 records. 1635 records eliminated during the screening for various reasons (case report, other languages, book chapter, unavailable text/conference abstract, unrelated topic). The number of articles used in the final synthesis was 90. A variety of clamps for use during the endurance test of tendons were identified and categorized according to the temperature used during the measurement. Based on this, the clamps are divided into three groups: room temperature, cooled or heated clamps. CONCLUSIONS: On the basis of the systematic literature review, mechanical parameters determined by usage with cooled clamps proved to be more reliable than with those at room temperature and with heated clamps. The collected information from the articles included name of clamp, author and date, type of clamps, type of endurance test (static or dynamic), type preloading (dynamic or static), type of tendon and measured and calculated parameters given in Table 3. summarized. The main advantage of the cooled clamps is that there is no limit to the type and length of the tendon. This study provides an overview of clamps and does not represent the modernity of any method.
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Tendones , Fenómenos Biomecánicos , Elasticidad , Humanos , Tendones/trasplante , Resistencia a la Tracción , Trasplante HomólogoRESUMEN
Echinacea purpurea (L.) Moench (EP)is a perennial herbaceous flowering plant, commonly known as purple coneflower and it belongs to the Asteraceae family. The Echinacea genus is originally from North America, in the United States, and its species are widely distributed throughout. There are nine different species of Echinacea, but only three of them are used as medicinal plants with wide therapeutic uses: Echinacea purpurea (L.) Moench, Echinacea pallida (Nutt.) Nutt. and Echinacea angustifolia DC. Several significant groups of bioactive compounds with pharmacological activities have been isolated from Echinacea species. Numerous beneficial effects have been demonstrated about these compounds. The immunomodulatory effect was initially demonstrated, but over time other effects have also been highlighted. The present review gives a comprehensive summary of the chemical constituents, bioactive compounds, biological effects and therapeutical uses of purple coneflower. Research shows that such a well-known and recognized species needs to be further studied to obtain efficient products with a guarantee of the safety.
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Dog harnesses are becoming more popular, with their large variety stemming from the idea that different dogs and scenarios require different types of harnesses. While their benefits over collars are self-explanatory, there is a lack of research on their effect on gait, and even the existing studies examine only a limited set of parameters. The goal of present study was to establish a method capable of quantifying canine gait in detail. Based on 3D motion capture, the developed method allows for the examination of 18 joint angles and 35 spatio-temporal parameters throughout multiple gait cycles, and can be used to analyze canine movement in detail in any kind of scenario (e.g. comparing healthy and lame dogs, or measuring the effect of training). The method is presented through the measurement of how different harnesses affect walking kinematics compared to free (unleashed) movements. Four dogs with varying body sizes and breeds and multiple types of harnesses were included. Marker data was filtered using a zero-lag 6th order Butterworth-filter with a cutoff frequency of 20 Hz. The normality of the spatio-temporal and joint range of motion parameters was tested using the Anderson-Darling test (p = 0.05), with most parameters passing in 60+% of test cases. Swing time and range of motion of the sagittal aspect of spinal angle at T1 vertebrae failed more regularly, both resulting from the measurement setup rather than the actual parameters being not normally distributed. Two-sample Kolmogorov-Smirnov tests (p = 0.05) were used to compare each parameter's distribution between cases, showing that most parameters are significantly altered by the harnesses in about 2/3rd of the cases. Based on the results, there's no absolute superior harness, however, it is possible to select the best fit for a specific dog and application, justifying their large variety.
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Análisis de la Marcha , Marcha , Animales , Fenómenos Biomecánicos , Perros , Análisis de la Marcha/veterinaria , Proyectos Piloto , Vértebras Torácicas , CaminataRESUMEN
Impaired mitochondrial function is associated with several metabolic diseases and health conditions, including insulin resistance and type 2 diabetes (T2DM), as well as ageing. The close relationship between the above-mentioned diseases and cardiovascular disease (CVD) (diabetic cardiomyopathy and age-related cardiovascular diseases) has long been known. Mitochondria have a crucial role: they are a primary source of energy produced in the form of ATP via fatty acid oxidation, tricarboxylic acid (TCA) cycle, and electron transport chain (ETC), and ATP synthase acts as a key regulator of cardiomyocyte survival. Mitochondrial medicine has been increasingly discussed as a promising therapeutic approach in the treatment of CVD. It is well known that vitamin B3 as an NAD+ precursor exists in several forms, e.g., nicotinic acid (niacin) and nicotinamide (NAM). These cofactors are central to cellular homeostasis, mitochondrial respiration, ATP production, and reactive oxygen species generation and inhibition. Increasing evidence suggests that the nicotinic acid derivative BGP-15 ((3-piperidine-2-hydroxy-1-propyl)-nicotinic amidoxime) improves cardiac function by reducing the incidence of arrhythmias and improves diastolic function in different animal models. Our team has valid reasons to assume that these cardioprotective effects of BGP-15 are based on its NAD+ precursor property. Our hypothesis was supported by an animal experiment where ageing ZDF rats were treated with BGP-15 for one year. Haemodynamic variables were measured with echocardiography to detect diabetic cardiomyopathy (DbCM) and age-related CVD as well. In the ZDF group, advanced HF was diagnosed, whereas the BGP-15-treated ZDF group showed diastolic dysfunction only. The significant difference between the two groups was supported by post-mortem Haematoxylin and eosin (HE) and Masson's trichrome staining of cardiac tissues. Moreover, our hypothesis was further confirmed by the significantly elevated Cytochrome c oxidase (MTCO) and ATP synthase activity and expression detected with ELISA and Western blot analysis. To the best of our knowledge, this is the first study to demonstrate the protective effect of BGP-15 on cardiac mitochondrial respiration in an ageing ZDF model.
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BACKGROUND AND PURPOSE: The small molecule BGP-15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP-15 in a rabbit model of atherosclerotic cardiomyopathy. EXPERIMENTAL APPROACH: Rabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks. BGP-15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium-dependent vasorelaxation was assessed and key molecules in the protein kinase G (PKG) pathway were examined by enzyme-linked immunosorbent assay (ELISA) and western blot. Passive force generation was investigated in skinned cardiomyocytes. KEY RESULTS: Both acute and chronic BGP-15 treatments improved the diastolic performance of the diseased heart. However, vasorelaxation and serum lipid markers were unaffected. Myocardial cyclic guanosine monophosphate (cGMP) levels were elevated in the BGP-15-treated group, along with preserved PKG activity and increased phospholamban Ser16-phosphorylation. PDE5 expression decreased in the BGP-15-treated group and PDE1 was inhibited. Cardiomyocyte passive tension reduced in BGP-15-treated rabbits, the ratio of titin N2BA/N2B isoforms increased and PKG-dependent N2B-titin phosphorylation elevated. CONCLUSIONS AND IMPLICATIONS: BGP-15 treatment improves diastolic function, reduces cardiomyocyte stiffness and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP-PKG pathway. As BGP-15 has been proven to be safe, it may be clinically useful in the treatment of diastolic dysfunction.
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Cardiomiopatías , Niacina , Animales , Cardiomiopatías/tratamiento farmacológico , Diástole , Ratones , Miocardio , Oximas , Piperidinas , ConejosRESUMEN
PURPOSE: To compare the effects of various types of ultrasound therapy (UST) on pain, function, and quality of life in patients with hip osteoarthritis. METHODS: Seventy-one patients receiving conventional physiotherapy (exercise, massage, and balneotherapy), were randomly allocated into four treatment groups: (1) continuous UST, (2) pulsed UST, (3) UST combined with transcutaneous electrical nerve stimulation (TENS), (4) placebo UST. We evaluated the hip pain (Visual Analog Scale), medication use, functional impairment (Western Ontario and McMaster Universities Arthritis Index; 6-minute walking test) and quality of life (SF-36) before, right after the treatments, and at 3 months follow-up. RESULTS: Resting pain improved significantly in all treatment groups at the follow-up visit compared to baseline (p (group1-4) ≤0.002). The proportion of patients achieving Minimal Clinically Important Improvement (MCII) in function at month 3 was the highest in group 3 (73%). The 6-minute walking test significantly improved in each group during the follow-up period (p (group1-4) ≤ 0.025). Pain (p (group1-4) ≤ 0.014) and general health domains of the SF-36 showed the greatest improvement (p (group 2-4) ≤ 0.018). CONCLUSIONS: There was no difference among the effects of various types of UST on pain, function, and quality of life in the treatment of hip osteoarthritis. Additional ultrasound treatment is not likely to increase the effect of the conventional therapy on pain and function in hip osteoarthritis.