Background Sarcopenia is a state with progressive and generalized loss of skeletal muscle mass and strength. It is a serious complication occurring in chronic kidney disease (CKD) patients which increases morbidity and mortality rate. Sarcopenia is diagnosed when loss of both compartments - muscle strength and skeletal muscle quality or quantity are present. However, there are still numerous patients, also with CKD, diagnosed as pre-sarcopenic individuals with low muscle strength and normal skeletal muscle quality or quantity and conversely, with correct muscle strength and decreased skeletal muscle mass, who are prone to develop sarcopenia in future life. It is crucial to examine numerous variables possibly associated with changes of skeletal muscle mass and muscle strength in terms of preventing the development of sarcopenia. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in advanced stages of CKD. Methods The study sample consisted of 84 non-dialysis dependent patients of both sexes (including 45.2% of women) with eGFR < 45 ml/min/1.73m2: 26.2% with eGFR 30-44 mL/min/1.73 m2, 65.5% with eGFR 15-29 mL/min/1.73 m2 and 8.3% with eGFR < 15 mL/min/1.73 m2. Muscle strength was estimated by measuring hand grip strength (HGS) with the use of handheld hydraulic dynamometer. Muscle quantity was measured by bioimpedance spectroscopy using Body Composition Monitor. Appendicular skeletal muscle mass (ASM) was calculated according to Lin’s formula. Serum creatinine, urea, uric acid and albumin were measured. Results In bivariate analysis we found that ASM significantly and positively correlated with anthropometric variables such as body mass (r=0.903, p

After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study we analyze whether there is a temporal window in which BMMC migrate more efficiently to damaged nerves while still retaining their positive effects. Adult Wistar rats of both sexes, with sciatic nerve crush were systemically transplanted with BMMC at different days post injury. Vehicle-treated, naïve, and sham rats were also included. Morphological, functional, and behavioral analyses were performed in nerves from each experimental group at different survival times. BMMC transplantation between 0 and 7 days after injury resulted in the largest number of nested cells within the injured sciatic nerve, which supports the therapeutic value of BMMC administration within the first week after injury. Most importantly, later BMMC administration 7 days after sciatic nerve crush was associated with neuropathic pain reversion, improved morphological appearance of the damaged nerves, and a tendency toward faster recovery in the sciatic functional index and electrophysiological parameters. Our results thus support the notion that even delayed BMMC treatment may represent a promising therapeutic strategy for peripheral nerve injuries.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms, and to determine if current data supports their future progression to clinical trials.

In this study, the fundamentals of electroencephalography signals, their categorization into frequency sub-bands, the circuitry used for their acquisition, and the impact of noise interference on signal acquisition are examined. Additionally, design specifications for medical-grade and research-grade EEG circuits and a comprehensive analysis of various analog front-end architectures for electroencephalograph (EEG) circuit design are presented. Three distinct selected case studies are examined in terms of comparative evaluation with generic EEG circuit design templates. Moreover, a novel one-channel battery-supplied EEG analog front-end circuit designed to address the requirements of usage protocols containing strong com-pound muscle movements is introduced. Furthermore, a realistic input signal generator circuit is proposed that models the human body and the Electromagnetic Interference from its surroundings. Experimental simulations are conducted in 50 Hz and 60 Hz electrical grid environments to evaluate the performance of the novel design. The results demonstrate the efficacy of the proposed system, particularly in terms of bandwidth, portability, common mode rejection ratio , gain, suppression of muscle movement artifacts, electrostatic discharge and leakage current protection. Conclusively, the novel design is cost-effective and suitable for both commercial and research single-channel EEG applications. It can be easily incorporated in Brain Computer Interfaces and neurofeedback training systems.

Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration of gemcitabine and docetaxel (Gem/Doce) as the first-line treatment in BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed treatment protocol set by the University of Iowa. Follow-up assessments were con-ducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with T1HG bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of CIS+T1HG. Median time to first recurrence in T1HG, CIS and T1HG+CIS groups was 11, 10.5 and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2% and 80.8% at 6, 9 and 12 months, respectively. The rate of progression-free survival was 100%, 98.1% and 92.3% at 6, 9 and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-up, as well as direct comparison of Gem/Doce and other anticancer agents, are essential.

In individuals with spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre-and post-intervention. The results revealed a preservation of muscle CSA in the Comb-NMES group compared to a control group receiving transcutaneous electrical nerve stimulation and passive movements. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI can attenuate inflammatory pathways linked to muscle atrophy and potentially promote muscle repair, advocating for its inclusion in early rehabilitation efforts. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Starvation of photoreceptors induced by reduced dysregulated ocular blood flow is proposed as a common pathway for the pathogenesis of retinitis pigmentosa (RP). The current study evaluated the safety and efficacy of ophthalmic nerve stimulation (ONS) as an ocular blood flow neuromodulator, combined with ascorbic acid (AA) as a potent anti-oxidant in the treatment of RP. Additionally, the initial characteristics of rod responders were identified. Forty participants with simple, non-syndromic RP presented with a characteristic triad of RP (the bone spicule pigmentation, attenuation of retinal blood vessels, and waxy optic disc pallor), were en-rolled in a prospective open-label single-armed interventional study. The severity of the disease was clinically graded into six stages. Patients with an established diagnosis of RP; aged ≥ 4 years, with best corrected visual acuity (BCVA) ≥ 20/400 were included. All participants were daily treated with bilateral ONS sessions combined with intravenous administration of AA for two weeks. The primary efficiency endpoint was 6 months’ changes in scotopic vision as measured by a 10-item, 100-point, Low Luminance Questionnaire-10 (LLQ-10). The secondary efficiency points included best corrected visual acuity (BCVA) and contrast sensitivity. Rod responders were defined by ≥ 25 points increment of LLQ-10 score at 6 months after treatment. The results showed that ONS combined with AA treatment significantly improved low luminance vision, BCVA, and contrast sensitivity in patients with RP (p≤ 0.05). At 6-month visit, twenty-four (60%) patients were identified as rod responders and 16 (40%) patients were rod-non-responders. The mean change in LLQ-10 score was (46.35 ±16.81) in rod responders versus (4.9 ± 7.6) in non-responders (p < 0.0001). A clinically significant improvement of BCVA (≥0.2 logMAR) and contrast sensitivity (≥0.3 log unit) were demonstrated in 50% of the right eyes of rod responders. No serious adverse effects were reported and headache in 5 patients (12.5%) was the only en-countered side effect in this study. In conclusion, ocular neuromodulation is a safe therapeutic strategy for RP. It significantly improved night vision, BCVA, and contrast sensitivity. Determinants of rod responders include a shorter duration of night blindness, an earlier stage of the disease, and a relatively thicker ganglion cell layer at baseline. Additionally, two therapeutic scenarios were recognized; an early disease-modifying intervention that restores night vision and reverses the disease process and a late cone rescue intervention that improves/maintains central vision.

Background and aims. Clinically significant delayed bleeding (CSDB) may complicate endoscopic colorectal submucosal dissection (ESD). Methods. We assessed the results of a prospective registry of colorectal ESD. We evaluated the effect of clip closure and PuraStat application for prevention of CSDB. Results. 40 patients with 41 colorectal ESD were included. ESD was successful in 38 lesions (92.7%), 35 with R0 resection (92.1%) and 33 with curative resection (86.8%). CSDB occurred in 3 out 38 lesions (7.9%, 95% CI [1.7 – 21.4%]), exclusively after rectal ESD (3 of 22 rectal lesions vs. 0 of 16 colonic lesions, p = 0.249). Clip closure was more frequently used after colonic ESD (12 of 16 colonic lesions vs. 2 of 22 rectal lesions, p < 0.001) and was not protective for CSDB in univariate analysis, even though no events occurred after clip closure (0 of 14 lesions with clip closure vs. 3 of 27 lesions without, p = 0.283). PuraStat was more frequently applied after ESD for rectal lesions (16 of 22 rectal lesions vs. 2 of 16 colonic le-sions, p < 0.001) and was not protective for CSDB, all three events occurring after PuraStat application (3 of 21 lesions with PuraStat application vs. 0 of 20 lesions without, p = 0.097). Conclusions. CSDB occurred exclusively after rectal ESD, and no predictive factors were identified in uni-variate analysis. Clip closure and PuraStat application were not protective for CSDB.

As times goes, the survival was improved attributed to target therapy and chemotherapy. Metastasis to skeletal muscle tissue is rare. Herein, we reported a case presenting with deep venous thrombosis but skeletal muscle metastasis. Though it was rare, oncologist shoud be keep in mind due to worse prognosis .

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

Lean body mass (LBM) is correlated with powerlifting performance in athletes competing in different bodyweight classes. However, it remains unknown whether changes in LBM are correlated with performance changes in powerlifters preparing for a competition. Aim of the study was to investigate the changes in LBM and performance in powerlifters preparing for a competition. Eight male powerlifters (age 31.7±9.8years, height 1.77±0.06m, weight 99.2±14.6kg) and three female powerlifters (age 32.7±16.3years, height 1.54±0.06m, weight 66.6±20.9kg), participated in the study. Athletes followed individualized periodized training programs for 12 weeks aiming to maximize their performance for the national championship. Maximum strength (1-RM) in squat, bench press, and deadlift, body composition, grip strength, anaerobic power, quadriceps’ cross sectional area and vastus lateralis muscle architecture were measured before and after the training period. Significant increases were found after the training period in squat (5.8±7.0%, P

With an increase in proportion of elderly patients, the global burden of spinal disease is on the rise. Likewise, there has been an increasing trend in the number of spine surgeries being performed worldwide. As we know, rehabilitation following spine surgery is critical for optimal recovery. However, current literature lacks consensus regarding the appropriate post operative rehabilitation protocol. The goals of rehabilitation after lumbar spine surgery are to improve physical and psychosocial function and may include multiple modalities such as physical therapy, cognitive behavioral therapy, specialized instruments, and instruction to be followed during activities of daily living. In recent years, not only are a greater number of spine surgeries being performed, various different techniques of lumbar spine surgery and spinal fusion have emerged. Physical therapy programs need to be curated after assessing the functional status of the patient by using various patient reported outcome measures and taking into consideration the technique of spinal fusion used and the muscle groups involved in these surgeries. By doing so it is possible to assess the level of functional impairment and then specifically target strengthening of those muscle groups affected by surgery whilst also improving impaired balance and allowing return to activities of daily living. We reviewed available literature pertaining to the history of spinal rehabilitation, the popular patient reported outcome measures used and different rehabilitation methods with the purpose of summarizing the current guidelines for postoperative rehabilitation after spine surgery and to introduce the rehabilitation after lumbar surgeries that we provide at our hospital.

This review delves into the growing field of flexible and stretchable strain sensors utilized in human gait analysis, focusing on determining knee bending angle and muscle activities when a human subject walks. Recent advancements have enabled these sensors to accurately capture biomechanical parameters while accommodating the body's natural movements. We examine the principles underlying these sensors' design and fabrication techniques, emphasizing their flexibility, stretchability, and biocompatibility for seamless integration into wearable systems. Through critical evaluation of existing methodologies, we assess the reliability and validity of these sensors in quantifying gait parameters. Furthermore, we discuss this technology's clinical and research implications, highlighting its potential in personalized rehabilitation and sports performance optimization. We provide an overview of flexible strain sensors and their application for analyzing human walking gait, especially for observing walking gait in rehabilitation programs. First, we present the basic working principles of various flexible strain sensors. Second, by the application of flexible strain sensors as walking gait monitoring. Finally, current challenges and future opportunities in this research area are discussed. By synthesizing current knowledge and outlining future directions, this review aims to provide insights for researchers and practitioners seeking to leverage flexible and stretchable strain sensors for comprehensive human gait analysis.

(1) Background: Neurologic and musculoskeletal diseases represent a considerable portion of the underlying etiologies responsible for the widely prevalent symptoms of pain, weakens, numbness, and paresthesia. Because of the subjective and often nonspecific nature of these symptoms, different diagnostic modalities have been explored and utilized.; (2) Methods: Literature review; (3) Results: Nerve and muscle biopsy remains the gold standard for diagnosing many of the responsible neurological and musculoskeletal conditions. However, the need for invasive tissue sampling is diminishing as more investigations explore alternative diagnostic modalities. Because of this, it is important to explore the current role of neurosurgical intervention for nerve and muscle biopsies and its current relevance in the diagnostic landscape of neurological and musculoskeletal disorders. With consideration of the role of nerve and muscle biopsy, it is also important to explore innovations and emerging techniques for conducting these procedures. This review explores the indications and emerging techniques for neurological intervention for nerve and muscle biopsies; (4) Conclusions: The role of neurosurgical intervention for nerve and muscle biopsy remains relevant in diagnosing many neurological and musculoskeletal disorders. Biopsy is especially relevant as a supportive point of evidence for diagnosis in atypical cases. Additionally, emerging techniques have been explored to guide diagnostics and biopsy, conduct less invasive biopsies, and reduce risks of worsening neurologic function and other symptoms secondary to biopsy.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

In the last three decades the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because of their role in signalling acting. Here we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling both in physiological and pathological conditions.

As a key mediator of chronic pain, neurotrophin nerve growth factor (NGF) binds to two neurotrophin receptors: p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor A (TrkA). The formation of the p75NTR-NGF-TrkA complex is implicated in the potentiation of chronic pain signals, making it an attractive target for therapeutic explorations. NGF analogues and monoclonal antibodies (mAbs) targeting NGF represent two distinct approaches in modulating the intricate signaling pathways involved in pain transduction mediated by the p75NTR-NGF-TrkA complex. While NGF analogues offer the advantage of tailored design to fine-tune neurotrophic responses, monoclonal antibodies provide a more systemic and comprehensive blockade of NGF, inhibiting its interactions with both p75NTR and TrkA receptors. However, the use of mAbs may pose challenges related to potential side effects and interference with the physiological functions of NGF. As a result, balancing the benefits and drawbacks of the two approaches is critical for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain. In this study, therefore, a novel structural and biophysical approach was employed for the design of NGF analogues to suppress p75NTR-NGF-TrkA-related chronic pain signaling. Employing high-throughput structural modeling and biophysics-based intermolecular binding affinity calculations, this article for the first time puts forward a set of NGF analogues, including in particular NGF analogues with four site-specific mutations, for whose dimerizations the K d at 37 ^◦C were reduced by three orders of magnitude (from 10^-9 M to 10^-6 M) compared to the K d at 37 ^◦C for the dimerization of native NGFs. Overall, the integration of structural and biophysical perspectives enhances our understanding of the rational design of NGF analogues as promising candidates for the development of NGF-targeted analgesic therapies, which balances the benefits and drawbacks of anti-NGF antibodies and NGF analogues for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain.

The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.

Several epidemiological studies and intervention trials have demonstrated that flavanols present in grapes and blueberries can lower the risk of cardiovascular disease. However, the mechanisms of action of these compounds remain unclear due to their low bioavailability. A polyphenol-rich grape and blueberry extract (PEGB) contained about 16% flavanol, of which 11% was monomer and 4% was dimer. A sensory test investigated the oral perception of a PEGB. At concentrations where quercetin had almost no detectable taste, PEGB exhibited significant astringency. Furthermore, in comparing the redox properties against O2･- using a luminescence method, PEGB acted as a prooxidant at low concentrations, promoting O2･-production and scavenging O2･-at high concentrations under pH conditions similar to oral cavity and intestine. In contrast, quercetin showed antioxidant activity at any concentration. A single oral administration of PEGB to rats showed a significant increase in skeletal muscle arteriolar blood flow. According to these results, PEGB containing flavanols displays a potent astringent flavor, increases O2･-production at low concentrations in a neutral pH environment as well as oral and intestine, and considerably enhances blood flow to skeletal muscles after a single dose in rats. The results of this study indicate a need to investigate the causal relationship between oral perception, redox properties, and bioactivity of polyphenols.

Background/Objectives: PEMF therapy has gained significant attention due to its potential benefits in promoting tissue repair and improving overall well-being. Recent publications in the field of exercise physiology, showed that pulsed electromagnetic fields (PEMFs) enhanced the velocity and the quantity of muscle O2 available and the rate of muscle oxygen extraction and utilization, in semi-professional cyclists, during a heavy constant-load exercise. In this paper, we investigate the effect of stimulation on muscular activation, in sedentary young people, during a constant-load exercise, performed at moderate intensity. Methods: Nine male sedentary young people, partic-ipated in this study. The response of the muscle activity, was recorded by surface EMG and assessed measuring the root mean square (RMS) normalized to the peak of the maximum voluntary con-traction. Data were collected in the right vastus Medialis (RVM) and right Biceps Femoris (RBF) at the baseline (standstill sitting), on warm-up (unloaded cycling) and during 30 minutes of con-stant-load exercise, in two experimental conditions (PEMF ON vs PEMF OFF). Results: The mul-tivariate analysis of variance performed on RVM showed a significant effect of PEMF in both warmup and exercise, while on RBF showed a significant effect of PEMF and warmup. Conclusions: PEMF strongly enhanced the amplitude of muscle activity in young sedentary people. The increase in the amplitude of the muscular response may lead to a higher oxygen consumption and release.

Pain is a multifaceted multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central-stimulation (tDCS) and peripheral-stimulation (TENS) in pain-inhibition during a cognitive-task in healthy volunteers and to observe potential neuro-cognitive improvements. Healthy eighty volunteers went through a complete experimental protocol comprising pain-induction (CPT), administration of tDCS/TENS, EEG-data acquisition, and cognitive assessments. The protocol for this study is categorized into 04-groups: G1(Control), G2(TENS), G3(Anodal-tDCS), and G4(Cathodal-tDCS). Paired t-tests (p

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

This article objective was to identify a centenary trend in the growth and development of girls in the metropolis of Moscow. Material and methods — The physical development (body length and weight, chest circumference, right hand muscle strength, and menstrual function development) of Moscow girls was studied during the period from 1920 to 2020. The amount of own observations was 4581 girls aged 8-17 years. Results – A comparative analysis of the physical development of Moscow school girls of different decades revealed a statistically significant increase in body length by 3-5 cm and a significant increase in chest circumference in all age groups of girls of the beginning of the XXI century, compared with their peers in the 1960s and 1980s, which indicates the completion of the gracialization processes that have been observed since the 1980s. However, in all age groups, a decrease in the muscle strength of the right hand is still being noticed. Earlier terms of menarshe onset in modern Moscow school girls (12 years 9 months) and a shift in growth jumps to earlier terms were established. It is shown that the age of menstruation depends on the level of family wealth. Conclusions. In Moscow girls in the centenary dynamics, a tendency to increase the total body size and shift the terms of biological maturation to earlier terms was revealed.

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE), on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) on individuals with supraspinatus tendinopathy. Participants (n=50) were divided into two groups, they received 4 treatment sessions, one per week, of PE and PNS (n=25) or 10 treatment sessions of TENS and US (n=25). Both groups performed EE program consisted of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p&lt;0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied.

This study analyzes the efficacy of trapezius muscle electromyography (EMG) in discerning mental states, namely stress and meditation. Fifteen healthy participants were monitored to assess their physiological responses to mental stressors and meditation. Sensors were affixed to both the right and left trapezius muscles to capture EMG signals, while simultaneous electroencephalography (EEG) was conducted to validate cognitive states. Our analysis of various EMG features, considering frequency ranges and sensor positioning, revealed significant changes in trapezius muscle activity during stress and meditation. Notably, low-frequency EMG features facilitated enhanced stress detection. For accurate stress identification, sensor configurations can be limited to the right trapezius muscle. Furthermore, the introduction of a novel method for determining asymmetry in EMG features suggests that applying sensors on bilateral trapezius muscles can improve the detection of mental states. This research presents a promising avenue for efficient cognitive state monitoring through compact and convenient sensing.

Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided bra-chial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 ml kg-1), and eight received lidocaine constant rate infusion (CRI) (2 mg kg-1 IV, followed by 100 µg kg-1 minute-1). Rescue analgesia was provided with Fentanyl IV. Carprofen was administered at the end of surgery. Post-operative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered accord-ing to pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to no rabbits in BPB. How-ever, rabbits in both groups had similar pain scores and there was no difference in administration of postoperative analgesia. There were no significant differences in food intake or faeces produc-tion over 18 hours, and no significant differences in distance travelled, or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively both groups were comparable.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

Vascular anomalies are a diverse group of abnormal blood vessel developments that can occur at birth or shortly afterward. Embolization and sclerotherapy have been utilized as a treatment option for these malformations but may cause moderate to severe pain. This study aims to evaluate the utilization of peripheral nerve blocks in opioid consumption, pain scores, and length of stay. A retrospective chart review was conducted at the UPMC Children's Hospital of Pittsburgh for all patients who underwent embolization and sclerotherapy between 2011 and 2020. Patient data was collected to compare opioid consumption, pain scores, and length of stay. Eight hundred fifty-four procedures were performed on 347 patients. The morphine milligram equivalent per kilogram mean ratio between groups was 0.9 (0.86, 0.95) with a p-value of &lt;0.001. The pain score mean ratio was –1.17 (–2.2, -0.1) and a p-value of 0.027. Length of stay had a mean ratio of 0.94 (0.4, 2) and a p-value of 0.875. By decreasing opioid consumption and postoperative pain scores, peripheral nerve blocks may have utility in patients undergoing embolization and sclerotherapy while not clinically increasing the length of stay for patients. Their use should be individualized and carefully discussed with the interventional radiologist.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Plantar flexors (PF) spasticity is known to poorly correlate with active dorsiflexion (DF) impairment throughout the swing phase of hemiparetic gait. Spastic Cocontraction, instead, stemming from descending pathways, potentially misdirect antagonist PF activity opposing DF during swing. Electromyographic (EMG) recordings, while unable to differentiate between reflex-based and descending origins, may offer valuable insights into this distinction by exploring PF EMG activity after tibial nerve neurotomy (which eliminates PF spasticity). Eleven subjects with hemiparesis walking at comfortable velocity and 11 controls walking at comfortable and slow velocity, underwent kinematic and PF/DF EMG analysis. Five of the hemiparetic subjects underwent tibial neurotomy &gt;1 year prior. We evaluated spasticity at rest (Tardieu scale), maximal ankle dorsiflexion, tibialis anterior agonist recruitment and gastrocnemius medialis and soleus cocontraction coefficients during swing. At slow velocity, controls (0.80±0.12 m/s) moved at a similar pace as hemiparetic subjects (0.73±0.37 m/s, NS). Hemiparetic subjects showed: (i) reduced ankle DF across swing (ii) increased PF cocontraction, including before any DF (iii) higher cocontraction despite absent spasticity in tibial neurotomy subjects (iv) higher tibialis anterior recruitment. Increased PF cocontraction occurs in the absence of spasticity or ankle DF despite higher agonist recruitment. Spastic cocontraction is a major factor limiting active DF at swing, unlike spasticity.

Thyroid surgery rates have tripled over the past 3 decades making it one of the most frequently performed procedures within general surgery. They are associated with the possibility of serious postoperative complications having a significant impact on the patient's quality of life. The recurrent laryngeal nerve (RLN) palsy and the external branch of the superior laryngeal nerve (EBSLN) palsy are, next to hypoparathyroidism and bleeding after operation, one of the most common complications. The introduction of neuromonitoring into thyroid surgery, enabling both confirmation of anatomical integrity and assessment of laryngeal nerve function, was a milestone that has begun a new era in thyroid surgery. The International Neural Monitoring Study Group made standardization of the technique of RLN and EBSLN monitoring during thyroid and parathyroid surgery which increased prevalence of neural monitoring during thyroidectomy. Current status of IONM and benefits of its use have been presented in this publication.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration trough animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, in a one health perspective. This review offers a hands-on vision about the non-invasive and conservative approaches on peripheral nerve injury, focusing the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities, such as low-level laser therapy and ultrasounds. In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoiding situations of permanent monoplegic limbs that could lead to amputation.

Burn patients still represent an important challenge in critical care medicine today. These patients can develop significant neurological conditions up to intracranial hypertension, but as they find themselves hospitalized outside of neurocritical care and are often subjected to sedation for the complex management, they are sometimes underestimated. The aim of this study is to evaluate the feasibility of non-invasive methods for the early diagnosis of intracranial hypertension in these patients. In this prospective observational study, adult burn patients admitted to intensive care within the first 8 hours of the event were enrolled. These patients were studied through ultrasound measurement of optic nerve sheath diameter and intracranial vessel velocimetry with transcranial Doppler. In the 20 patients studied, no frankly pathological values were identified in the 3 different measurement stages (within 8 hours of the burn, then at 48 and 96 hours) and no correlations were identified between the measured values and the extension of the burn with the related risk of mortality. However, this study, one of a kind, demonstrates that these non-invasive methods are applicable to this specific patient population, and can represent an effective method for reducing the incidence of complications that are dangerous for survival.

Alzheimer’s Disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, the latter termed cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) within the cerebrovasculature and its potential associations with CAA, gender, and ApoE4 genotype. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher colocalization of HS with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebral vasculature was detected in AD patients with severe CAA, suggesting a potential role in CAA development. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings shed light on the intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further exploring the underlying mechanisms may present novel therapeutic avenues for AD treatment.

(1) Background: Ultra-endurance exercise involves a high physical impact, resulting in muscle damage, inflammatory response and production of free radicals that alter the body's oxidative state. Supplementation with antioxidants, such as beetroot, may improve recovery in ultra-endurance runners. The aim of this study was to determine whether there is a correlation between the beetroot intake and the recovery of serum oxidative status, inflammatory response and muscle damage parameters after an ultra-endurance race. (2) Methods: An observational and longitudinal study was conducted by means of surveys and blood samples collected from 32 runners during the IX Penyagolosa Trails CSP® race and the two following days. The variables C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase (CK), the activity of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the oxidative damage markers malondialdehyde (MDA), carbonyl groups (CG) and loss of muscle strength using the Squat Jump test (SJ) were analyzed to discriminate whether beetroot consumption can modulate the recovery of ultra-trail runners. (3) Results: Significant differences were observed between runners who ingested beetroot and those who did not, in terms of oxidative status, specifically in serum GPx activity at 24 and 48 hours, muscle damage variables CK and LDH and in SJ test at the finish line. Therefore, the intake of supplements containing beetroot positively influences the recovery of serum oxidative status and muscle damage after ultra-endurance running.

Background: Granular cell tumor is a benign neurogenic tumor of the subcutaneous and submucosal area. The tongue is the most affected site of the oral cavity. The clinical presentation is non-specific and manifests as a submucosal nodule or mass. Because of its non-specific presentation, a definitive diagnosis an only be established after a histopathological examination and an immunohistochemical study to search for a neurogenic origin. Methods: We report the case of a 48-year-old man who was referred for the management of a nodular lesion on the tip of his tongue that had increased in size over the previous three months. Results: A complete surgical excision was performed for the histopathological exam, and an immunohistochemical study confirmed a strong expression of S100 and CD68. A diagnosis of granular cell tumor was confirmed. There was no recurrence et three years follow-up. Conclusion: the GCT is a rare tumor of nervous origin of the oral mucosa, it is non-specific in expression, with a good prognosis after complete excision. the histological and immunohistochemical diagnosis of the lesion is essential for the diagnosis.

The presence of valuable bioactive compounds in European eel (Anguilla anguilla) skin was studied. For it, proximate and lipid class compositions and analysis of the fatty acid (FA) profile (individual FAs; FA groups, i.e., saturated, monounsaturated, and polyunsaturated; FA ratios, i.e., polyunsaturated/saturated, ω3/ω6) were determined and compared to the composition of the eel muscle. As a result, higher (p&lt;0.05) levels of proteins (271.6 g·kg-1), lipids (38.0 g·kg-1), ash (27.7 g·kg-1) and ω6 FAs were observed in the skin tissue. Contrary, the muscle tissue showed higher (p&lt;0.05) moisture, ω3 FA and ω3/ω6 values. Regarding lipid classes, a higher (p&lt;0.05) proportion of phospholipids (111.1 g·kg-1 lipids), sterols (104.7 g·kg-1 lipids), α-tocopherol (274.0 mg·kg-1 lipids), and free fatty acids (43.6 g·kg-1 lipids) was observed in the skin tissue. No differences (p&gt;0.05) between both tissues could be detected for triacylglycerol and FA group (saturated, monounsaturated, and polyunsaturated) values, as well as for the polyunsaturated/saturated ratio. It is concluded that eel skin, a by-product resulting from commercial processing, can be considered a valuable source to provide the food and pharmaceutical industries with useful value-added constituents such as proteins, lipids, ω3 FAs, phospholipids, and α-tocopherol.

Background: According to EWGSOP2, the diagnosis of sarcopenia is confirmed when in addition to low muscle strength, low muscle quantity or quality is present. Echo intensity (EI) determined by muscle ultrasound (US) has been proposed as an efficient method for the assessment of muscle quality. The effect of changing various US parameter settings on EI remains unclear. Therefore, the aim of this study was to assess the differences between EI values obtained by adjusting parameter settings over their entire range in a sample of middle-aged healthy subjects. Methods: Thirty-two repeated US scans of rectus femoris (RF) and rectus abdominis (RA) muscles were taken in eight men and three women with a portable Mindray M7 premium US machine, working in an Extended field-of-view, B-Mode setup, equipped with a linear 5.0-10.0 MHz transducer. The following US parameters and settings were fixed: gain 60dB, depth 6.5cm, and frequency 10 MHz. Readily adjustable parameters were dynamic range (DR), gray map (GM), line density, persistence, and IClear. A default setting DR65 was chosen as the reference setting. For each of the parameters, the settings of one single parameter of interest was changed over its entire range following a standardized protocol. The EI values were calculated using the open-source software ImageJ. Repeated measures analyses were performed to evaluate the effect of parameter settings on EI. Linear interpolation was used to determine non-significant ranges across a given parameter. Results: For the RF muscle, the EI values were significantly different across DR (p<0.001), GM (p<0.001), and IClear (p<0.001). Post hoc analysis confirmed the differences within these three settings. Echo intensity values within the range of DR55 to DR80 were not significantly different. For the RA muscle, the EI values were significantly different across DR (p=0.004) and GM (p=0.030). Post hoc pairwise comparisons revealed no significant difference with the default setting, except for DR150 (p=0.042). Conclusion: We showed that EI values differ across the DR and GM range, especially in the RF. We suggest using a DR setting within its midrange to minimize the effect of machine setting-dependent factors on EI values. These findings reconfirm the need for standardization of ultrasound echo intensity settings when applied for diagnostic purposes of muscle quality.

The practical problem-solving of incidental unreliability of intraoperative neuromonitoring may be the simultaneous neurophysiological recording and the inspection of the surgical field through the camera (the "Real-time neuromonitoring" concept). This would allow the immediate warning of the surgeon on the possibility of the spinal structures insult during but not after the application of the standard procedures in scoliosis surgery (the “Interactive verbal surgeon-neurophysiologist neuromonitoring" concept). This study aimed to compare the advantages, utility, reliability, and time-consuming of both intraoperative neuromonitoring scenarios using non-invasive and innovative recordings from peroneal nerves (PER) versus tibialis anterior muscles (TA) with surface electrodes of motor evoked potentials (MEP) bilaterally as a result of transcranial magnetic (TMS) or electrical (TES) stimulations. Studies were performed in two similar groups ("Real-time neuromonitoring", N=60 and "Interactive verbal sur-geon-neurophysiologist neuromonitoring", N=60) of patients treated surgically because of mainly Lenke 2 type idiopathic scoliosis (IS) pre- (T0), intra- (T1 – before surgical procedures, T2 – after surgical procedures) and postoperatively (T3) as well as in healthy volunteers (N=60, Control). The cumulative parameters of MEP amplitudes and latencies recorded from PER compared to those recorded from TA in healthy volunteers were approximately 67% (1100µV) lower at p=0.007 and 10.6% shorter (3.1 ms) at p=0.04, respectively. A similar trend was also observed in patients from both groups at each follow-up stage. MEP recordings from TA and PER in patients of both groups differed similarly in T0-T3 compared to controls at p=0.008-0.04. MEP parameters in all patients induced by TMS (T0) and TES (T1) did not differ. The parameters of MEP amplitudes recorded from TA and PER intraoperatively in T1 and T2 differed at p=0.04-0.03, indicating the bilateral improvement of neural spinal conduction due to the surgical intervention. Parameters of TMS-induced MEP amplitudes in T3 further increased bilaterally compared to the tests recorded in T0 at p=0.03-0.02. In both groups of patients, an average 51,8 BIS level of anaesthesia minimally affects the variability of the MEP amplitude, especially in PER recordings when ap-plied TES strength was at 98.2 mA. The number of MEP parameter fluctuations, mainly the amplitudes decreasing, was strictly associated with the neurophysiologist's warnings due to transpedicular screws implantation, corrective rods implantation, distraction, derotation, and compression procedures, respectively; at p=0.04-0.03 more in patients from the “Interactive S-N neuromonitoring” group. The average duration of the surgery was significantly shorter (p=0.04) by about 1 hour in the "Real-time neuromonitoring" group. The number of two-way communications between the surgeon and neurophysiologist and vice versa in the "Real-time neuromonitoring" group was reduced by approximately half at p=0.008. The study's results prove the advantages of using the "Real-time neuromonitoring" procedure in increasing safety and non-invasiveness, shortening the time, and lowering the costs of surgical treatment of patients with pathological lateral curvature of the spine. The modifications of the MEP nerve conduction recording technology with surface electrodes from nerves presented in this study enable precise and reliable information on the patient's neurological condition at every stage of applied surgical procedures, even in conditions of slight fluctuations in the anaesthesia.

The homeostasis of cellular calcium is fundamental for many physiological activities, while calcium levels maintain inhomogeneous within cells. During the onset of asthma, epithelial and inflammatory cells secrete platelet derived growth factor (PDGF), inducing proliferation and migration of airway smooth muscle (ASM) to the epidermal layer, narrowing the airway. The regulation of ASM cells by PDGF is closely related to the conduction of calcium signals. In this work, we generated subcellular-targeted FRET biosensors to investigate calcium regulations at different compartments of ASM cells. PDGF-induced cytoplasmic calcium [Ca2+]C increase was attributed from both extracellular calcium influx and endoplasmic reticulum (ER) calcium [Ca2+]ER release, which was partially regulated by PLC-IP3R pathway. Interestingly, removal of extracellular calcium influx led to inhibited ER calcium release, likely through inhibitory effect on calcium-dependent activation of ER ryanodine receptor. Inhibition of L-type calcium channel on plasma membrane, or SERCA pump on ER resulted in both reduced [Ca2+]C and [Ca2+]ER from PDGF stimulation, while IP3R channel inhibition led to reduced [Ca2+]C only. Inhibited SERCA pump caused immediate [Ca2+]C increase and [Ca2+]ER decrease, indicating an active calcium exchange between cytosol and ER storage in resting cells. PDGF-induced calcium at outer mitochondrial membrane sub-region showed similar regulatory response to cytosolic calcium, not influenced by inhibition of mitochondrial calcium uniporter channel. Therefore, our work identified calcium flow pathways among extracellular medium, cell cytosol, and ER by regulatory calcium channels. Particularly, extracellular calcium flow has an essential function to fully activate ER calcium release.

Abstract: A progressive neurological disorder was observed in a male neutered Weimaraner. Clinical signs included fecal incontinence, lethargy, moderate paraparesis, proprioceptive pelvic limb ataxia, falling, cognitive decline, incoordination, decreased interest in food, changes in posture, and episodes of trance-like behavior. Neurologic signs were first observed at approximately 4 years, 10 months of age and progressed slowly. Magnetic resonance imaging showed generalized brain atrophy with areas of white matter pathology. Humane euthanasia was elected at 6 years, 7 months of age due to increasing severity of the neurological signs. Autoflorescent intracellular granules were observed in the cerebral and cerebellar cortexes, optic nerve, and cardiac muscle of the affected dog. These abnormal inclusions in the cerebral cortex and cardiac muscle immunolabeled with antibodies to mitochondrial ATP synthase subunit c protein, like that observed in the neuronal ceroid lipofuscinosis group of lysosomal storage diseases. Immunolabeling also demonstrated pronounced neuroinflammation in brain tissues. The ultrastructural appearances of the disease-related inclusion bodies in the brain and optic nerve were quite variable. The ultrastructure and locations of many of the inclusions in the nervous tissues suggested that they were derived, at least in part, from the myelin surrounding axons. The storage bodies in the cardiac muscle were located in mitochondria-rich regions and consisted of parallel arrays of membrane-like components interspersed with electron-dense flocculent material. The disease was characterized by pronounced abnormalities in the myelin of the brain and optic nerve consisting of distinctive areas of ballooning between the layers of myelin. The whole genome sequence generated from the affected dog contained a homozygous G-to-A missense mutation in CNP, which encodes proteins with CNPase enzyme activity and a structural role in myelin. The mutation predicts a Thr42Met amino acid sequence substitution. Genotyping of archived Weimaraner DNA samples identified an additional G>A variant homozygote with a clinical history and brain lesions similar to those of the proband. Of 292 Weimaraners and over 4,000 other dogs of various breeds, the proband and the other Weimaraner that exhibited similar signs were the only two that were homozygous for the CNP missense variant. CNPase immunolabeling was widespread in brain tissues from normal dogs but was undetectable in the same tissues from the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the late-onset Weimaraner disorder likely results from the missense mutation that results in CNPase deficiency, leading to myelin abnormalities, accumulation of lysosomal storage bodies, and brain atrophy. Similar disorders have been associated with different CNP variants in Dalmatians and in human subjects.

Keywords: Adrenergic signaling in cardiomyocytes; cardiac muscle contraction; Chagas disease; diabetic cardiomyopathy; dilated cardiomyopathy; glycerolipid metabolism; glycolisis/glucogenesis; hypertrophic cardiomyopathy; purine metabolism; steroid hormone biosynthesis.

FacioScapuloHumeral Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders, and is linked to the inappropriate expression of the DUX4 transcription factor in adult muscles. The deregulated molecular network causing FSHD skeletal muscle dysfunction and pathology is still not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4 induced cell death. In this study, we further explore the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knock-down in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.

The central nervous system (CNS) controls movements and regulates joint stiffness with muscle coactivation, but until now few studies have examined muscle pairs during running. This study aims to investigate differences in lower limb muscle coactivation during gait at different speeds from walking to running. Nineteen healthy runners walked and ran at speeds ranging from 0.8 km/h to 9.3 km/h. Twelve lower limb muscles' coactivation was calculated using the time-varying multi-muscle coactivation function (TMCf) with global, flexor-extension, and rostro-caudal approaches. Spatiotemporal and kinematic parameters were also measured. We found that TMCf, spatiotemporal and kinematic parameters were significantly affected by gait speed for all approaches. Significant differences were observed in the main parameters of each coactivation approach, and in the spatiotemporal, and kinematic parameters at the transition between walking and running. Positive and negative strong correlations were found between global coactivation parameters and center of mass displacements, as well as some spatiotemporal parameters, regardless of gait speed. Our findings suggest that walking and running have different coactivation patterns and kinematic characteristics, with the whole-limb stiffness exerted more synchronously and stably in running. The coactivation indexes and kinematic parameters could be the result of global coactivation, which is a sensory-control integration process used by the CNS to deal with more demanding and potentially unstable tasks like running.

Caused by age or trauma, collapsed connective tissue can cause nerve entrapment and damage within the tarsal tunnel. Tarsal tunnel syndrome is relatively underdiagnosed. This study presents an intervention targeting damaged tissues surrounding the nerves and replacing the structural cushioning with a Wharton’s jelly tissue allograft. The eight selected patients from four clinical sites had tarsal tunnel-related defects. Patient outcomes were tracked on a 90-day calendar utilizing the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster University Arthritis Index (WOMAC). All patients had failed standard care practices for at least six weeks. Each patient received a Wharton’s jelly tissue allograft to sites around the affected tarsal tunnel. No patients experienced adverse reactions. Percent change calculated from the initial application to the 90-day follow-up showed an improvement of 59.43% in NPRS and a 37.58% improvement in WOMAC. This study provides evidence that WJ allograft applications are safe, minimally invasive, and efficacious for patients who have failed standard care treatments for tissue defects associated with Tarsal Tunnel syndrome. Limitations include the small cohort size and nonblinded nature. The results of this study warrant further research to confirm the efficacy, optimal dose, protocol, and durability of Wharton's jelly.

TMEM16A is a Ca2+-activated Cl- channel expressed in various species and tissues. In mammalian skeletal muscle precursors, the activity of these channels is still poorly investigated. Here, we characterized TMEM16A channels and investigated if the pharmacological activation of Piezo1 channels could modulate the TMEM16A currents in mouse myogenic precursors. Whole-cell patch-clamp recordings combined with the pharmacological agents Ani9, T16inh-A01 and Yoda1 were used to characterize TMEM16A-mediated currents and the possible modulatory effect of Piezo1 activity on TMEM16A channels. Western blot analysis was also carried out to confirm the expression of TMEM16A and Piezo1 channel proteins. We found that TMEM16A channels were functionally expressed in fusion-competent mouse myogenic precursors. The pharmacological blockage of TMEM16A inhibited myocyte fusion into myotubes. Moreover, the specific Piezo1 antagonist Yoda1 positively regulated TMEM16A currents. The findings demonstrate, for the first time, a sarcolemmal TMEM16A channel activity and its involvement at the early stage of mammalian skeletal muscle differentiation. In addition, the results suggest a possible role of mechanosensitive Piezo1 channels in the modulation of TMEM16A currents.

Skeletal muscles are crucial for voluntary movements, and impairments in their function significantly impact our activity. Dysferlin, a protein predominantly present in skeletal muscle, is a focal point of extensive research due to its vital role in muscle repair and maintenance. This study investigates Dysferlin's levels and function in skeletal muscles, emphasizing its significance and the potential effects of its dysregulation on fast and slow muscle fibers. We employed Western blotting on two different rat muscles. The results revealed distinct expressions of Dysferlin in fast and slow fibers, as demonstrated by Western blotting. We propose that Dysferlin may have a metabolic role in addition to its involvement in the repair mechanism.

Emotional experiences are a part of our lives. The maladaptive functioning of an individual's emotional field can lead to emotional disturbances of various kinds, such as anxiety and depression. Currently, there is an increasing prevalence of emotional disorders that cause great human suffering and high socio-economic costs. Emotional processing has a biological basis. The major neuroscientific theories of emotion are based on biological functioning, and all of them take into account the anatomy and function of the tenth cranial nerve: the vagus nerve. The vagus nerve connects the subdiaphragmatic and supradiaphragmatic areas and modulates emotional processing as the basis of interoceptive functioning. Auricular vagus nerve stimulation is a new and innovative neuromodulation technique based on the function of the vagus nerve. Several interventions have shown that this new neurostimulation technique is a very promising resource for treating emotional disorders. In this paper, we summarise three neuroscientific theories of emotion, explain what transauricular vagus nerve stimulation is, and present arguments for its use and continued research.

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in the elderly, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants of the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between Low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyzes were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived after a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pain. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise Lower ASM was moderately associated with LBP and knee pain, while higher ASM correlated with engagement in regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pain. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

Treatment options for sarcopenia are currently limited, primarily relying on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. Our objective is to investigate the relationship between nutrient intake and lean mass, function, and strength. Data were derived from the Gothenburg H70 birth cohort study in Sweden, including 719 70-year-olds born in 1944 (54,1 % females). For independent variables, the diet history method (face-to-face interviews) was used to estimate habitual food intake during the preceding three months. Dependent variables were gait speed (muscle performance), hand grip strength (muscle strength) and appendicular lean soft tissue index (ALSTI). Linear regression analyses were performed to analyze the relationship between the dependent variables and each of the covariates. Several nutrients were positively associated with ALSTI, such as polyunsaturated fatty acids (DHA, EPA), selenium, zinc, riboflavin, niacin equivalent, vitamin B12, vitamin D, iron, and protein. After correction for multiple tests, there were no remaining correlations with handgrip and gait speed. Findings of positive correlations for some nutrients with lean mass suggest a role for these nutrients for maintaining muscle volume. These results can be used to inform clinical trials to expand the preventive strategies and treatment options for individuals at risk of muscle loss and sarcopenia.

To win a taekwondo competition, more points must be scored, and the key to scoring points is to improve the motor performance of the kick. The wing kick is an offensive and defensive maneuver. Core stability appears to be important for improving athletic performance, but the specific relationship and effect of core stability on athletic performance in the aerial phase of taekwondo is unclear. The aim of this study was to investigate the relationship between core stability and athletic performance in taekwondo in order to provide appropriate theoretical support for training and to help coaches and athletes to improve athletic performance. A total of 16 subjects (height: 167.34±9.2 cm; weight: 61±8.96 kg; age: 24.7±3.25 years) were studied. Data were captured using 13 infrared cameras at 120Hz, kinematic and kinetic data were captured using a motivated motion capture system, and the data were exported to Visual3D in order to calculate the execution time of the aerial phase, the angular momentum of the left lower extremity, and MVC analysis of the EMG using EMG works. The core stability level of the subjects were measured using the Sahrmann Core Stability Test (SCST) to correlate with the other data, and then the subjects were grouped according to their core stability levels and the data from both groups were analyzed with t-tests. Results During the double fly lifting of aerial segments, SCST levels showed a very strong negative correlation with execution time (r= -0.739) and there was a statistically significant difference in execution time between high and low SCST levels (p &lt; 0.001), and the desired negative correlation was also seen in lower limb angular momentum X-axis (thigh r= -0.6294, shank r= -0.536, foot r= -0.6175), especially in the X-axis. The left rectus femoris (LRF) data had greater activation in the low SCST group(p=0.0019*). Through this experiment, we found that athletes with high core stability had faster execution times, lower angular momentum, and higher core muscle activation. Therefore, we conclude that incorporating core stability training into taekwondo training has the potential to improve kicking performance.

Functional ankle instability (FAI) results from multiple ankle sprains, causing a perceived sense of joint instability due to muscle and ligament imbalances. Neuromuscular training (NMT) is employed to enhance ankle stability in individuals with FAI. The study included 24 male university students with FAI, who underwent ankle NMT on three surfaces. OpenSim musculoskeletal model analyzed the effects on ankle muscle activity, kinetics, and kinematics. Utilizing repeated measures analysis of variance (ANOVA) and one-dimensional statistical non-parametric mapping (SNPM1d) to identify distinctions between training surfaces. NMT on foam cushion (FC) significantly enhanced tibialis anterior (TA) and gastrocnemius medial (GM) activation during walking compared to level-ground (LG) and artificial turf (AT) (p&lt;0.05). However, no differences observed for peroneus longus (PL), gastrocnemius lateral (GL), and peak ankle plantarflexion (PF). During jogging and fast running, post FC training increased TA, PL, GM, GL activation, and peak ankle PF moment (p&lt;0.05). Additionally, post FC training, subtalar mobility was significantly reduced (p&lt;0.05), and ankle joints exhibited greater dorsiflexion (DF) angles during jogging and fast running (p&lt;0.05). Consequently, selecting FC for short-term ankle NMT proves more advantageous in enhancing ankle stability among individuals with FAI, yielding a more positive impact on FAI improvement.

Aim: the main aim of this study is to compare the onset of effectiveness of mental nerve block with lingual infiltration and inferior alveolar nerve block on patients visiting dental hospital for extraction of mandibular anterior teeth. Materials and methods: The study was set in a clinical setting. This was a randomized controlled double-blind cross study, where 25 subjects received two treatments at an interval of at least 1 week in a within a dental hospital.Inferior alveolar nerve block and lingual nerve block injection is given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered for the right side. Mental nerve block along with lingual infiltration of the corresponding tooth was given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered on the left side.Visual analogue scale (VAS) was used in this study, which consists of a scale with range of 0-10 pain severity on which 0 indicated absence of pain and 10 the worst pain possible. The patients were asked to give scores corresponding to his/her pain, after IANB, mental nerve block and lingual infiltration and these scores were recorde.Results: From the results we can see that patients gave scores between 3-4, stating that they had moderate pain during extraction after administration of IANB (54%) (graph 2) and VAS scores of 0-1 were given by patients, which is suggestive of no pain during extraction after administration of Mental nerve block and lingual nerve infiltration (62%)Conclusion: Within the limits of the study we can conclude that mental nerve block along with lingual infiltration is an effective way to completely and quickly anaesthetise the central incisor to the 1st premolar region.

Segmental bone defects caused by trauma, infection, tumor resection or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard to restore function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in incorporation with host bone as well as cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells and urine-derived stem cells for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hopeful in the future that these preclinical results will translate into new therapies for bone defect repair.

Background & aims: Malnutrition in lung transplant (LT) candidates increases postoperative morbidity and mortality. Early diagnosis of malnutrition could attenuate adverse prognostic factors. This study aimed to assess the prevalence of nutritional risk and malnutrition using GLIM criteria in LT candidates and clinically characterize those with malnutrition. Methods: A prospective longitudinal study was conducted from 2000 to 2020 of LT candidates who underwent complete nutritional assessment (nutritional screening, anthropometry, bioelectrical impedance, blood laboratory tests and malnutrition diagnosis using GLIM criteria). Results: Obstructive diseases (45.6%), interstitial diseases (36.6%) and cystic fibrosis/non-cystic fibrosis bronchiectasis (15.4%) were the main conditions assessed for LT. Of the 1060 candidates evaluated, 10.6% were underweight according to BMI, 29% were at risk of malnutrition and 47% were diagnosed with malnutrition using GLIM criteria. Reduced muscle mass was the most frequent GLIM phenotypic criterion. Malnutrition was more prevalent in patients with cystic fibrosis/non-cystic fibrosis bronchiectasis (84.5%), obstructive (45.4%) and interstitial (31.3%) diseases. GLIM criteria detected some degree of malnutrition in all diseases requiring LT and identified patients with higher CRP levels and worse respiratory function, anthropometric measurements and visceral protein and lipid profiles. Conclusions: LT candidates present a high prevalence of malnutrition using the GLIM algorithm. GLIM criteria detected malnutrition in all diseases requiring LT and defined patients with worse clinical-analytical profiles.

Sporadic inclusion body myositis (sIBM) is the most common muscle disease of older people and is clinically characterized by slowly progressive asymmetrical muscle weakness, predominantly affecting quadriceps, deep finger flexors and foot extensors. At present there are no enduring treatments for this relentless disease that eventually leads to severe disability and wheelchair dependency. Although sIBM is considered a rare muscle disorder, its prevalence is certainly higher as the disease is often undiagnosed or misdiagnosed. The histopathogical phenotype of sIBM muscle biopsy includes muscle fiber degeneration and endomysial lymphocytic infiltrates that mainly consist of cytotoxic CD8+ T cells surrounding nonnecrotic muscle fibers expressing MHCI. Muscle fiber degeneration is characterized by vacuolization and accumulation of congophilic misfolded multi-protein aggregates, mainly in their non-vacuolated cytoplasm. Many players have been identified in sIBM pathogenesis including environmental factors, autoimmunity, abnormalities of protein transcription and processing, accumulation of several toxic proteins, impairment of autophagy and ubiquitin proteasome system, oxidative and nitrative stress, endoplasmic reticulum stress, myonuclear degeneration, and mitochondrial dysfunction. Aging has been also proposed as a contributor to the disease. However, the interplay between these processes and the primary event that leads to the coexistence of autoimmune and degenerative changes is still under debate. Here, we outline our current understanding of disease pathogenesis, focusing on degenerative mechanisms, and discuss the possible involvement of aging.

Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the bladder real-time need. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimize the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morpho-physiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the nerve fasciculate nature and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications.

This paper presents a thorough review of Electrical Muscle Stimulation (EMS) in the context of Augmented Reality (AR) and Virtual Reality (VR), specifically focusing on its application in providing kinesthetic feedback. Our systematic review of 17 studies reveals the growing interest and potential of EMS in this domain, as evidenced by the growing body of literature and citations. Key elements presented in our review encompass a catalog of the applications developed to date, specifics of the stimulation parameters used, the participant demographics of the studies, and the types of measures used in these research efforts. We discovered that EMS offers a versatile range of applications in AR/VR, from simulating physical interactions like touching virtual walls or objects, to replicating the sensation of weight and impact. Notably, EMS has shown effectiveness in areas such as object handling and musical rhythm learning, indicating its broader potential beyond conventional haptic feedback mechanisms. However, our review also highlights major challenges in the research, such as inconsistent reporting of EMS parameters and a lack of diversity in study participants. These issues underscore the need for improved reporting standards and more inclusive research approaches to ensure wider applicability and reproducibility of results.

A stable match, an intercuspated maxilla-mandible relation is the universally accepted goal for dental restorative interventions, yet the underlying sensorimotor mechanisms to achieve this goal in the natural jaw closure remains to be elucidated. Dentists have intuitively regarded peripheral sensory innervation from tooth contacts as a significant control element for jaw muscle actions, both in the state of health and in cases of pathological dysfunction. However, therapeutical interventions for reshaping the dental arch anatomy and jaw relations have not always been successful. Repetitive masticatory chewing cycles, swallowing, talking, as well as volitional jaw-opening and -closing involve stereotyped neural commands from the central nervous system that are modulated in reaction to the sensory afferent feedback from the peripheral neurons and their sensor organs. The aim of this article is to describe, on a fraction of a second time-scale, the minuscule tilts and kinematic events of mandible during the making of a stable match with maxilla. Evidence of the importance of tooth contacts as the sensorimotor motivation of each of the successive kinematic steps of the “mandible-meets-maxilla-narrative” are discussed.

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17β-estradiol, a major estrogen component, directly affects energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 3D 31P FID-MRSI to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases when their blood 17β-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17β-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17β-estradiol but display a high correlation between EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC).The robust association we have identified between ATP-referenced PCr and 17β-estradiol suggests that 17β-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It was demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and on lung fibroblast lines derived from fibrotic lungs but it is almost absent in control lines and tissue. CCL18 induces receptor-internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduces CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knock-down of CCR6 in a mouse fibroblast cell line abolishes the induction of collagen and -smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

BACKGROUND: Functional constipation can lead to painful defecations, fecal incontinence, and abdominal pain, significantly affecting a child's quality of life. Treatment options include non-pharmacological and pharmacological approaches, but some cases are intractable and require alternative interventions like neuromodulation. A subtype of neuromodulation, called Transcutaneous Posterior Tibial Nerve Stimulation (TPTNS), comprises electrical stimulation at the ankle level, by means of electrodes fixed to the skin. TPTNS is a minimally invasive, easy-to-apply technique that can potentially improve constipation symptoms in the pediatric population by stimulating the sacral nerves. AIM: To evaluate the clinical results and applicability of TPTNS as an adjuvant treatment for children and adolescents with functional constipation. METHODS: Between April 2019 and October 2021, 38 patients diagnosed with functional constipation according to the Rome IV Criteria were invited to participate in the study. The study followed a single-center, uncontrolled, prospective cohort design. Patients received TPTNS for 4 or 8 weeks, with assessments conducted immediately after the periods of TPTNS and 4 weeks after the end of the intervention period. The data normality distribution was determined by the Shapiro-Wilk test. Wilcoxon test and Student's t-test for paired samples were used to compare quantitative variables, and the McNemar test was used to compare categorical variables. RESULTS: Of the 38 enrolled patients, 28 children and adolescents with intractable function constipation completed the study, receiving TPTNS for 4 weeks. Sixteen patients (57.1%) extended the intervention period for 4 extra weeks, receiving 8 weeks of intervention. TPTNS led to significant improvements in stool consistency, frequency of defecation, and bowel function scores, with a reduction in abdominal pain. Quality of life across physical and psychosocial domains showed substantial enhancements. The quality of life-related to bowel habits also improved significantly, particularly in lifestyle, behavior, and embarrassment domains. The positive effects of this intervention are seen relatively early, detected after 4 weeks of intervention, and even 4 weeks after the end of the intervention. TPTNS was well-tolerated, with an adherence rate of approximately 78%, and no adverse effects were reported. CONCLUSION: TPTNS is an adjuvant treatment for intractable functional constipation, improving bowel function and quality of life. The effects of TPTNS were observed relatively early and sustained even after treatment cessation.

Takotsubo syndrome (TTS) is a cardiomyopathy that presents clinically as a transient and reversible left ventricular wall motion abnormality (LVWMA) that can recover spontaneously within hours to weeks. Studies have shown that it mainly affects older people. Postmenopausal women in particular have an increased prevalence. Physical and emotional stress are widely discussed and generally recognized trigger factors. As age also appears to play a major role in the development of TTS, this review will take a closer look at age- and gender-specific aspects. First and foremost, postmenopausal women and the associated lower oestrogen concentration should be mentioned here. Another important role is played by the hypothalamic-pituitary-adrenal (HPA) axis and the associated glucocorticoid-dependent negative feedback and the resulting immune response. Inflammaging is another term that is increasingly used in connection with TTS. In the following, these risk factors are considered in more detail and linked to the increased sympathetic activity as a possible consequence of chronic stress. Based on the imbalance between the sympathetic and parasympathetic nervous system, we venture an explorative proposal and would like to present a new possible therapeutic approach.

Implantation of two electrical stimulators of different cranial nerves in one patient is rare. We report the case of a forty-seven-year-old patient already implanted with a trigeminus nerve stimulator. In addition, this patient suffered from hearing problems. In one ear, the patient was deaf. On the other side, the patient wore a bone conduction hearing aid to improve hearing. In this complex situation, we decided to check the possibility of cochlear implantation on the deaf side. Finally, we managed to provide electrical stimulation of the auditory pathway of the deaf ear to improve the patient’s hearing tests. In addition, this case report shows how the trigeminus stimulator interferes with the electrical stimulation in auditory evoked potentials measurements of the auditory brainstem and cortex via EABR (evoked auditory brainstem response) resp. EALR (evoked auditory late response).

Muscle fatigue caused by using staplers affects the surgical procedures of surgeons. Compared to manual staplers, electric staplers decrease the muscle fatigue by replacing repeated gripping and releasing with automatic model. Still powered by the battery, the electric staplers are confronted with new operation fatigue due to the extra weight of the battery. The weight and manual operation of the electric stapler can cause user's muscle fatigue. To tackle the unsettled fatigue issue, the study is to propose a new design method to offset the influence of extra weight of the battery attached to the electrical stapler by changing the opening and closing of the stapler end clamp to electric control. The purpose of this study is to verify whether the design of this electric stapler can offset the impact of weight. Experiments are set up to test the feasibility of the design on 12 male Chinese surgeons. The muscle fatigue is indicated by measuring the EMG (electromyography) signal, and the stapler's working effect is indicated by measuring the end movement of the stapler. The result shows the new-designed stapler reduce the operation fatigue, counteracting the impact of the battery weight.

Hundreds of thousands of people living along the Yatsushiro Sea coast have been exposed to methylmercury from the contaminated water of the Chisso factory in Minamata. Methylmercury causes neurological deficits in the cerebrum and cerebellum, with symptoms of ataxia, dysarthria, and visual field constriction in severe cases, but the most common symptom of a milder disorder is somatosensory disturbance due to parietal lobe damage. We investigated the characteristics of the somatosensory disturbances in detail by studying subjective complaints, neurological findings, and quantitative sensory tests in 197 residents (63.2 ± 10.7 years old) from contaminated areas exposed to methylmercury from seafood and 130 residents (63.7 ± 9.3 years old) from control areas. The most commonly affected sensory modalities were superficial peripheral touch and pain in the extremities, followed by two-point discrimination and deep senses, and in the most severe cases, full-body sensory dysfunction and impairment of all sensory submodalities. Although the severity of the sensory submodalities correlated with each other, there was almost no correlation between the severity of these submodalities and indices of peripheral nerve conduction studies, suggesting that the primary cause of the sensory deficits was damage to the central nervous system. The health effects of chronic methylmercury toxicosis can be elucidated by a detailed examination of sensory deficits.

We aimed to determine whether A-mode ultrasound (US) can provide accurate and reliable measurements comparable to those obtained through B-mode US, under diverse conditions. Thirty healthy participants (15 female, 15 male) underwent measurements of subcutaneous fat thickness (SFT), muscle thickness (MT), and muscle quality (MQ) in the trapezius and biceps brachii muscle with both US modes after and before exercises designed to stimulate the respec-tive muscles. In three key indices, the results demonstrated high validity of A-mode, with min-imal mean differences between the two devices less than 0.91mm and intraclass correlation coef-ficients exceeding 0.95 at all measures. Also, Correlation coefficients between error scores and average scores for the trapezius and biceps brachii muscles suggested no evidence of systematic error. The trapezius MT and MQ significantly increased, and biceps brachii MT significantly in-creased after exercise (p<0.05). Notably, both A-mode and B-mode exhibited the same tendency in these post-exercise changes in muscle. This study suggests that low-cost and low-resolution A-mode US provides measurements of SFT, MT, and MQ similar to more expensive, high-resolution B-mode imaging. A-mode US can serve as an affordable and portable alternative for muscle assessment.

(1) Background: During physical exercise, ventilation (VE) adapts to the intensity and characteris-tics of the effort. The breathing pattern is defined as the relationship between the tidal volume (VT) and breathing frequency (BF) for a given VE. The aim of this study was to evaluate whether inspiratory muscle training influenced the response of the breathing pattern during an incremen-tal effort in amateur cyclists. (2) Methods: 18 amateur cyclists completed an incremental test to exhaustion with gas analysis on a cycle ergometer and spirometry. Cyclists were randomly as-signed to two groups (IMTG=9; CON=9). The IMT group completed 6 weeks of inspiratory muscle training (IMT) using a PowerBreathe K3® device at 50% of the maximum inspiratory pressure (Pimax). The workload was adjusted weekly. After the 6-week intervention, the cyclists repeated the incremental exercise test with gas analysis and spirometry. The response of the breathing pat-tern was evaluated during the incremental exercise test. (3) Results: Pimax increased in the IMTG (p<0.05; +19.62%). Variables related to the breathing pattern response showed no differences be-tween groups after the intervention (EXPvsCON; p>0.05). Likewise, no differences were found in the IMTG after training (PREvsPOST; p>0.05). (4) Conclusions: IMT improved the strength of in-spiratory muscles and sports performance in amateur cyclists. These changes were not attributed to alterations in the response of the breathing pattern.

The correlation between pain and emotional status in subjects with temporomandibular disorders (TMD) is known. Regardless of that up to date these findings were seldomly confronted with the objective assessment of pain using a digital algometer on the mastication muscles. The aim of the study was to investigate the relationship between the emotional status, chronic pain pain pressure threshold (PPT). 38 subjects were screened for the existence of temporomandibular disorders with the 3Q/TMD questionnaire, for chronic pain (GCPS) and emotional status (PHQ-9 and GAD-7). The results were confronted with the PPT measured with the digital algometer on the masseter muscles. Each subject was examined three times (after 1 month and after 7 months from the initial exami-nation session. Chronic pain scores (GCPS) were found to be higher in the TMD group in all three examination sessions (p<0,05). The pain, depression and anxiety levels were higher in females de-spite the existence of TMD, but only some were significant.A correlation between chronic orofacial pain scores and PPT was found in 2 out of 3 examination sessions. The PPT scores on the masseter muscles did not correlate with the emotional state in the study population.

Due to the still large number of patients diagnosed with pelvic neoplasms (colorectal, gynecological, and urological) in advanced stages right from the initial diagnosis, surgery represents the mainstay of treatment, often implying wide, eventually multi-organ resections in order to achieve negative surgical margins. Perineal wound morbidity, particularly in extralevator abominoperineal excision, leads to complications and local infection rates of up to 40%. Strategies to reduce postoperative wound complications are pursued to address this issue.The VRAM flap remains the gold standard for autologous reconstruction after pelvic oncological resection; it was initially designed for abdominal wall defects and later expanded for large pelvic tissue defects.The flap's application is based on its physical characteristics, including abundant tissue and a generous skin paddle, which effectively obliterates dead space after exenterations. The generous skin paddle offers good cosmetic and functional outcomes at the recipient site.This article describes the case of a patient histopathologically diagnosed with stage IIIA squamous cell carcinoma of the uterine cervix who received multimodal onco-surgical treatment. The surgical mainstay of this treatment is pelvic exenteration. Pelvic reconstruction after this major surgery was performed using a vertical flap with the rectus abdominis.

(1) Background: This manuscript introduces the "Lines and Dots" (LAD) technique, a novel method for administering Botulinum Toxin Type A (BoNT-A) in treating horizontal forehead lines. This technique emphasizes precision in targeting nerve endplates, considering individual anatomical variations, and optimizing treatment efficacy. (2) Methods: The LAD technique focus on using the frontalis muscle contraction dynamics to identify the specific distribution of the supraorbital and supratrochlear nerves It involves creating a grid of predetermined lines and points on the forehead that align with nerve paths and motor endplate zones. (3) Results: By targeting injections along these precise lines and points, the LAD technique ensures more effective utilization of BoNT-A. This approach not only enhances the toxin's effect but also allows for a reduction in the overall dosage. The strategic placement of injections results in a more natural, symmetrical, and sustained therapeutic effect, ensuring an improved aesthetic outcome. (4) Conclusions: The LAD technique represents a significant advancement in the realm of cosmetic injectables. It offers a tailored, patient-specific approach, maximizing the effectiveness of BoNT-A injections for treating forehead lines while minimizing risks and enhancing patient satisfaction. This method underscores the importance of a deep anatomical understanding and precision in cosmetic procedures.

Epigenetic modifications play a significant role in determining the fate of AFSC in terms of differentiation into multiple lineages. There is a tight correlation among DNA methylation, histone modifications, and small noncoding RNAs during the epigenetic control of stem cells differentiation. The present study investigates the role of miRNAs in differentiation of AFSC and addresses how their unique signatures contribute to lineage-specific differentiation. miRNAs profile was assessed in AFSC after 4 weeks of endothelial and muscular differentiation. Our results showed a decreased expression of for 5 miRNAs (miR-125b-5p, hsa-miR-18a-5p, hsa-miR-137, hsa-miR-21-5p and hsa-let-7a-5p) and an increased expression for 12 miRNAs (miR-134-5p, miR-103a-3p, let-7i-5p, miR-214-3p, let-7c-5p, miR-129-5p, miR-210-3p, let-7d-5p, miR-375, miR-181-5p, miR-125a-5p, hsa-let-7e-5p) in EPC compared with undifferentiated AFSC. Smooth muscle differentiation of AFSC revealed significant changes in 9 miRNAs from total of 84 tested; 3 were downregulated (miR-18a-5p, miR-137, sa-miR-21-5p) and 6 were upregulated (miR-155-5p, miR-20a-5p, let-7i-5p, hsa-miR-134-5p, hsa-miR-214-3p, hsa-miR-375). miRNAs are molecular regulators of cell fate and differentiation, recent advances in molecular biology techniques revealed miRNA regulatory networks that can provide us information of endothelial and muscle cell biology in terms of homeostasis, growth, differentiation, and vascular function.

The management of shoulder instability in children and adolescents is a challenging field of orthopaedics. There are several complicating factors which originate from the variable underlying cause that is often a unique combination of traumatic factors, ligamentous laxity, and the pattern of muscle contractility. As the cause is often multifactorial, this makes interpretation of the literature difficult as nomenclature is variable. The purpose of this review is to shed light on the nuances of paediatric and adolescent shoulder instability.

Hypoxia-inducible factor (HIF)-1α represents the oxygen-sensitive subunit of HIF transcriptional factor, usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expression. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. We herein analyzed HIF-1α expression and localization in differentiating murine C2C12 myoblasts and SCs under normoxia and evaluated matrix metalloproteinase (MMP)-9 as a HIF-1α target, by biomolecular, biochemical, morphological and electrophysiological analyses. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression, differently from the more elongated and parallel-aligned cells, likely ready to fuse with each other, which show mainly a cytoplasmic localization of the factor. Multinucleated myotubes displayed both a nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. Short-interfering RNA silencing of HIF-1α and MMP-9 and MMP-9 pharmacological inhibition unraveled MMP-9 as HIF-1α downstream effector and HIF-1α/MMP-9 axis essential for the morpho-functional cell myogenic commitment.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on prediabetes is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as prediabetes is a reversible condition if it is detected in the early stages. Literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes remain unknown. In this review, we seek to review the existing literature on prediabetic and T2DM associated changes in skeletal muscle function.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardiac-skeletal muscle coupling during exercise was then elucidated. The exercise capacity via cardiopulmonary exercise testing (CPX), cardio-ankle vascular index (CAVI), and body composition of 101 patients with AMI were measured at discharge. Patients were categorized based on their CAVI into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0–8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and peak VO2 (VO2 Peak) during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak in patients with AMI. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply defines systemic exercise limits in patients with AMI. This suggested that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

This experiment was conducted to study the effects of Cyfluthrin (Cy) exposure on neurobehaviour, hippocampal tissue and synaptic plasticity in Wistar rats. First, high-dose Cy exposure can cause nerve injury with symptoms such as deficits in learning and memory ability, spatial exploration and autonomic motor ability. Moreover, it was found that medium- and high-dose Cy exposure can cause disordered energy metabolism in hippocampal cells and an abnormal release of the neurotransmitter Glu. Second, pathological brain sections showed that the middle and high doses of Cy caused deformation, reduction and disorder of hippocampal pyramidal cells, a decrease in the number of Nissl bodies, pyknosis of the hippocampal cell nuclear membrane and serious damage to organelles, indicating that exposure to these doses of Cy may cause hippocampal tissue damage in rats. Third, with the increase in exposure dose, the morphological changes in hippocampal synapses were more obvious, including blurred synaptic spaces, decreased synaptic vesicles and a decreased number of synapses. Moreover, the expression levels of the key synaptic proteins PSD-95 and SYP also decreased in a dose-dependent manner, indicating obvious synaptic damage. Finally, the study found that medium and high doses of Cy could upregulate the expression of A2AR in the hippocampus, and the expression levels of inflammatory factors and apoptosis-related proteins increased in a dose-dependent manner. Moreover, the expression of A2AR mRNA was correlated with neurobehavioural indicators, inflammatory factors, synaptic plasticity factors and apoptosis factors, suggesting that Cy may cause nerve damage in rats and has a close relationship with A2AR.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risks of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria, organelle where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

Background: Two types of medicinal systems are available in Korea: Western and oriental. These exist as separate services that independently provide medical care to patients. We determined the utility and benefits of compressive and integrated medical services (CIMS) comprising 12 sessions of acupuncture and healing programs over 6 weeks. Methods: In this two-group parallel single-center randomized controlled assessor-blinded trial, 24 participants were assigned to either the experimental (conventional medical treatment plus CIMS, n = 12) or control (conventional medical treatment, n = 13) group. Spinal nerve root block was performed on the compressed spinal nerve root (identified using magnetic resonance imaging) when no improvement was observed after the initial treatment. The experimental group received 12 cycles of acupuncture and manual therapy for 6 weeks; the control group received conventional medical treatment alone. Results: The average age of participants in the experimental and control groups was 70.73 ± 5.95 and 67.33 ± 8.89 years, respectively. There were no significant differences between the groups in terms of age, body mass index, Leeds Assessment of Neuropathic Symptoms and Signs, sex, and current medical history. We found high compliance for both programs (acupuncture and healing). On exclusion of between-group effects, the visual analog scale (VAS) score improved significantly over time (p = 0.045). Further, comparison of the groups after excluding the effects of visits revealed significantly lower VAS scores in the experimental group than in the control group (p = 0.000). Conclusions: Patients with degenerative lumbar spinal stenosis who mainly complain of radiating pain in the lower leg may benefit from CIMS after spinal nerve root block for ≤3 months after treatment. Our study findings suggest that this treatment improves spinal function and Oswestry Disability Index score. However, CIMS did not improve QoL.

The basis for computation in the brain is the quantum threshold of the ‘soliton’ accompanying the ion changes of the action potential and the refractory membrane at convergences. We provide a logical explanation from the action potential to a neuronal model of the coding and computation of the retina and have explained how the visual cortex operates by quantum phase processing. In the small world network parallel frequencies collide into definable patterns of distinct objects. Elsewhere we have shown how many sensory cells are mean sampled to a single neuron and that convergences of neurons are common. We have also demonstrated, using the threshold and refractory period of a quantum phase pulse, that action potentials diffract across a neural network due to the annulment of parallel collisions in phase ternary computation (PTC). Thus, PTC applied to neuron convergences results in collective mean sampled frequency and is the only mathematical solution within the constraints of brain neural networks (BNN). In the retina and other sensory areas, we discuss how this information is coded and then understood in terms of network abstracts within the lateral geniculate nucleus (LGN) and visual cortex. First by defined neural patterning within a neural network, and then in terms of contextual networks, we demonstrate that the output of frequencies from the visual cortex contain information amounting to abstract representations of objects in increasing detail. We show that nerve tracts from the LGN provide time synchronisation to the neocortex (defined as the location of the combination of connections of the visual cortex, motor cortex, auditory cortex, etc). The full image is therefore combined in the neocortex with other sensory modalities so that it receives information about the object from the eye, and all abstracts that make up the object. Spatial patterns in the visual cortex are formed from individual patterns illuminating the retina and memory is encoded by reverberatory loops of computational actions potentials (CAPs). We demonstrate that a similar process of PTC may take place in the cochlea and associated ganglia, as well as ascending information from the spinal cord, and that this function should be considered universal where convergences of neurons occur.

Extensive damage to peripheral nerves is a health problem with few therapeutic alternatives. In this context, the development of tissue engineering seeks to obtain materials that can help recreate environments conducive to cellular development and functional repair of peripheral nerves. Different hydrogels have been studied and presented as alternatives for future treatments to emulate the morphological characteristics of nerves. Along with this, other research proposes the need to incorporate electrical stimuli into treatments as agents that promote cell growth and differentiation; however, no precedent correlates the simultaneous effects of the types of hydrogel and electrical stimuli. In this research, the neural differentiation of PC12 cells we are evaluated, relating the effect of collagen, alginate, GelMA, and PEGDA hydrogels with electrical stimulation modulated in four different ways. Our results show significant correlations for different culture conditions, allowing us to develop new experimental schemes for new materials in peripheral nerve engineering.

Injured peripheral nerves regenerate their axons in contrast to those in the central nervous system. However, functional recovery after surgical repair is often disappointing. The basis for the poor recovery is the progressive deterioration with time and distance, of the growth capacity of the neurons that lose their contact with targets (chronic axotomy) and the growth support of the chronically denervated Schwann cells (SC) in the distal nerve stumps. This is despite the retained capacity of chronically denervated and atrophic muscle to accept reinnervation. Progressive decline in regeneration associated genes in both axotomized neurons and denervated SCs accounts for the decline in regenerative success in association with silencing of neural activity in sensory neurons due to their disconnection from their sense organs and, in motoneurons due to loss of their synaptic contacts in the spinal cord. Whilst exogenous neurotrophic factors promote nerve regeneration, the profuse axonal outgrowth and difficulties in delivery are avoided by promoting their endogenous expression with brief (1 hour) low frequency (20Hz) electrical stimulation (ES) proximal to the injury site. ES accelerates axon outgrowth and in turn, target reinnervation in both animals and human subjects. Applying ES to intact nerve days prior to nerve injury, conditional ES (CES) increases axonal outgrowth and regeneration rate with the potential for application in nerve transfer surgeries and end-to-side neurorrhaphies. However, the additional surgery for applying CES electrodes may be a hurdle. ES is applicable in all surgeries with excellent outcomes.

Entrapment neuropathies of the lower limb are a misunderstood and underdiagnosed group of disorders, characterized by pain and dysesthesia, muscular weakness, and specific provoking movements on physical examination. The most frequent of these syndromes encountered in clinical practice are fibular nerve entrapment, proximal tibial neuropathy, sural nerve neuropathy, deep gluteal syndrome or sciatic nerve entrapment and lateral femoral cutaneous nerve entrapment, also known as meralgia paresthetica. They are commonly mistaken for lumbar plexopathies, radiculopathies, and musculotendinous diseases, which appear even more frequently and have overlapping clinical presentations. A comprehensive anamnesis, physical examination, and electrodiagnostic studies should help clarify the diagnosis. If the diagnosis is still unclear or a secondary cause of entrapment is suspected, magnetic resonance neurography, MRI or ultrasonography should be conducted to clarify the etiology, rule out other diseases and confirm the diagnosis. Moreover, clinicians should gain familiarity with this disease and their diagnostic confidence should increase, leading to early diagnosis of nerve damage and prevention of muscle atrophy. The reviewed and updated epidemiology, anatomy, pathophysiology, etiology, clinical presentation and EDX technique and interpretation of the entrapment neuropathies of the lower limb are further described in this article.

Introduction. Congenital muscular torticollis (CMT) is an asymmetrical head positioning resulting from structural changes in the sternocleidomastoid muscle (SCM) that occurs early in a child’s development period or due to perinatal trauma. Children with CMT exhibit a marked imbalance in tension between the SCMs. When the clinical picture is typical, an ultrasound scan is performed to reveal characteristic lesions, such as tissue fibrosis or post-traumatic changes. Early diagnosis of CMT in newborns and implementation of treatment offer the chance of a complete cure. Torticollis treatment aims to rebuild the SCM's normal function by restoring its anatomical length, normal cervical spine mobility and muscle flexibility to enable regular head movements. Surgical treatment is performed when conservative methods fail to improve the patient’s condition. Indications for surgery include marked shortening of the SCM, persistent fibrosis in the muscle, constant head and facial asymmetry, and rotation or lateral flexion in the cervical spine restricted by > 15°. After hip dislocations and foot deformities, pediatric orthopedics addresses torticollis as the third most common congenital anomaly. Aim. This study was a retrospective analysis of 111 children diagnosed and treated due to CMT. Methods. The following were determined: the relationship between the side of CMT location and the type of delivery (cc vs. natural), between the body weight at birth and the side of CMT location, between the extent of SCM thickening and the type of delivery, and the incidence of CMT depending on the order of delivery. Results and conclusions. The analysis showed that CMT was more common in boys 61(54%) than in girls 51(46%), which may be related to the greater birth weight in boys. Of the pediatric patients with CMT, 76% were primiparous. More often, children born via natural delivery had left-sided torticollis with a more significant broadening of the SCM on ultrasound scans than right-sided torticollis. Theories of torticollis development pathophysiology should be deepened, systematized, and further researched.

The importance of various markers such as sclerostin, Dickkopf-1 (DKK-1), Irisin, receptor activator of NF-kB ligand (RANKL), and Vitamin D have been well studied in bone metabolism. Additionally, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and Interleukine-6 (IL-6) have been identified to hinder muscle protein synthesis, leading to the loss of muscle and strength. However, a research gap exists in the understanding their role in muscle function and physical activity. Therefore, this study aims to explore the serum levels of sclerostin, DKK-1, irisin, IL-6, RANKL, Vitamin D, and TNF-α and assess their relationships with upper and lower body strength in young adults. In this study, 38 college-aged students 18-23 years participated and completed the protocols. The participants’ lower and upper body strength were assessed by the vertical jump test (Just Jump, Probotic, AL) with a Tendo FitroDyne (Tendo Sports Machines, Trencin, Slovak Republic) and handgrip (HG) dynamometry (Takei Scientific Instruments, Yashiroda, Japan), respectively. Fasting morning blood samples were analyzed for serum levels of the biomarkers by ELISA. The results indicate significant sex differences in sclerostin, DKK-1, irisin, and vitamin D levels (p<0.05). Furthermore, a positive association was observed between sclerostin, DKK-1, and vitamin D, with lower body muscle performance variables (p<0.05). Conversely, a significant negative correlation was observed between TNF-α and upper-body muscle performance variables (p<0.05). The results suggest that these markers may have a distinct effect on muscle performance, underscoring the need for further investigation to elucidate the concept of muscle-bone crosstalk.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Thyroid surgery has been for years one of the most common elective procedures performed in general surgery. In the last 25 years, there have been significant advances in the diagnosis and treatment of thyroid disorders, and new technologies are being implemented. The aim of this study was to ana-lyze 25 years of experience in thyroid surgery in the Department of General, Minimally Invasive and Endocrine Surgery at the Medical University of Wroclaw in terms of demographic changes, indica-tions for surgical treatment, the type of thyroid surgery performed and complications. The impact of recent advances on changes in endocrine surgery was evaluated. For this purpose, clinical material from the years 1996-2020 was analyzed, with a total of 3748 patients (7285 RLN at risk of injury). Period I included the years: 1996-2003, period II: 2011-2015 and 2018-2020. Results: In the last 25 years, the percentage of patients operated on for thyroid cancer has increased threefold (p <0.00001); the extent of thyroid surgery has changed: in 1996-2003, subtotal thyroid operation was performed in more than 90% of patients vs. 1.7% of total thyroid gland surgery; 2011-2015 and 2018-2020 were more than 94% of total thyroid surgery vs. 4% of subtotal surgery (p<0.00001). The increase in the extent of surgery did not affect the percentage of total amount recurrent laryngeal nerve palsy (RLN palsy) (5.17% vs. 4.38% p = 0.1785), it did affect the percentage of transient RLN palsy in group II vs. group I (0.41% vs. 1.34%, p<0.00001), while the percentage of permanent RLN palsy in group I was statistically significantly higher than in group II (4.77% vs. 3.05%, p=0.0016). An increase in the percentage of postoperative clinical hypoparathyroidism in group II was observed: 4.84% vs. 8.93% (p<0.00001). Conclusions: Over 25 years, there has been a significant increase in the number of sur-geries performed for thyroid cancer, the range of surgeries from partial resections to total excision of the thyroid gland has changed, and the increased range of surgeries did not have a statistically signifi-cant effect on the number of vocal fold paralysis, but increased the percentage of postoperative hypo-parathyroidism. Intraoperative neuromonitoring had a significant impact on changing the scope of surgery and preventing complications.

Obesity in adolescents combined with the increased exposure time to electronic devices, enhances a sedentary lifestyle and is linked to the risk of developing musculoskeletal injuries. The aim of this study was to identify possible correlations between anthropometric characteristics, body composition, exposure time to electronic devices or screen time (ST) and physical activity (PA) level along with muscle power and dynamic knee valgus (DKV) in young athletes to avoid future injuries. A total of 125 adolescent basketball athletes (66.4% boys), 12 to 17 years old (13.94±1.58 years) participated. Anthropometric and demographic characteristics were recorded. PA level was assessed through IPAQ and ST through a single question from the HELENA study. The Counter Movement Jump test was used for the evaluation of the lower limb muscle power, while the Single Leg Drop Jump test was used for the evaluation of the dynamic knee valgus via two-dimensional (2D) kinematic analysis. The Pearson index showed a statistically significant positive correlation between muscle power and height (r=0.788, p<0.001), while the Spearman index showed a smaller but equally statistically significant positive correlation with BMI (rs =0.651, p<0.001) and age (rs=0.579, p<0.001). The ST (rs= -0.194, p=0.03) showed a weak negative correlation with DKV, while PA (r=0.85, p<0.001) showed a high, statistically significant, positive correlation. The anthropometric characteristics of adolescent athletes can determine their ability to produce muscle power. A high level of physical activity could play a key role in compensating and thus reducing the negative effects of high exposure to screen time on the dynamic knee valgus

The maintenance of skeletal muscle mass plays a fundamental role in health and issues associated with quality of life. Mechanical signals are one of the most potent regulators of muscle mass, with a decrease in mechanical loading leading to a decrease in muscle mass. This concept has been supported by a plethora of of human- and animal-based studies during the last 100 years and has resulted in the commonly used term of “disuse atrophy”. These same studies have also provided a great deal of insight into the structural adaptations that mediate disuse-induced atrophy. For instance, disuse results in radial atrophy of fascicles, and this is driven, at least in part, by radial atrophy of the muscle fibers. However, the ultrastructural adaptations that mediate these changes remain far from defined. Indeed, even the most basic questions, such as whether the radial atrophy of muscle fibers is driven by the radial atrophy of myofibrils and/or myofibril hypoplasia, have yet to be answered. In this review, we thoroughly summarize what is known about the macroscopic, microscopic, and ultrastructural adaptations that mediated disuse-induced atrophy and highlight some of the major gaps in knowledge that need to be filled.

Dielectric elastomer actuators (DEAs) offer robust, high energy density solutions for soft robotics. The proposed end effector consists of three spring roll configuration DEAs, each acting as a robotic finger, using a 3M VHB-F9473PC adhesive membrane. The lateral force, bending angle and response time of the actuator are measured experimentally and compared with the predictions of an analytical model. The cylindrical actuator measures 70 mm in length and 15 mm in diameter and achieved a lateral force of 30 mN, a bending angle of 6.8 ° and a response time of ≈ 1 s. Spring roll configuration DEAs are shown to reduce the effects of viscoelasticity seen in the membrane, making the actuator more controllable at higher voltages. The dielectric constant of the membrane is shown to be a limiting factor of actuation, with a decrease in dielectric constant resulting in larger actuation. The end effector successfully gripped numerous light objects for extended periods, showing the applicability of spring roll DEAs for soft end effectors.

The introduction of exoskeletons in the industry has focused on improving worker safety. Exoskeletons have the objective of decreasing the risk of injury or fatigue when performing physically demanding tasks. The exoskeleton’s effects on the muscles is one of the most common focus in the assessments. The present study aims to analyse the muscle interactions generated by using a passive lumbar exoskeleton during load-handling tasks in laboratory conditions with and without an exoskeleton. Electromyographic data of the muscles involved in the task were recorded from twelve participants performing load-handling tasks. Correlation Coefficient, Coherence Coefficient, Mutual Information, and Multivariate Sample Entropy were calculated to determine if there were significant differences in muscle interactions between the two test conditions. Results showed statistically significant differences for all pairs of muscles and indicated that the use of the exoskeleton implied more constant values throughout the exercise. The Directed Conditional Granger Causality was obtained to study the directionality of the interactions, with significant differences in two muscle pairs Gluteus-Quadriceps and Gluteus-Lumbar in the gravity-positive direction in both cases. In conclusion, EMG parameters chosen appear to be appropriate measurements for studying the exoskeleton effects over muscle couplings.

In the last decade there has been a growing interest in infrared thermography in the field of sports medicine in order to elucidate the mechanisms of thermoregulation. The aim of this study was to describe bilateral variations in skin temperature of the anterior thigh and patellar tendon in healthy athletes, to provide a model of baseline tendon and muscle thermoregulation in healthy sprinters following a unilateral isokinetic fatigue protocol. Fifteen healthy national-level sprinters underwent unilateral isokinetic force testing and electrostimulation in which body temperature was measured before, during, and after the protocol using an infrared thermographic camera. ANOVA detected a significant difference in the time x side interaction for patellar temperature changes (p≤0.001) and a significant difference in the time x side interaction for quadriceps temperature changes (p≤0.001). The thermal challenge produces homogeneous changes evident in quadriceps areas, but not homogeneous in tendon areas. these data show that metabolic and blood flow changes may depend on the physical and mechanical properties of each tissue.