Background/Objectives: The primary life-threatening complication in Spinal-bulbar muscular atrophy (SBMA) is ventilatory failure, which results from the weakening of the bulbar and respiratory muscles. However, systematic studies assessing respiratory function over the long-term have not been performed. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years, aiming to identify any potential, sustained decline during this time. Furthermore, we explored possible correlations between respiratory function tests and clinical and biochemical serum indices. Methods: We collected data from 9 genetically confirmed SBMA patients and conducted spirometric measurements twice a year for eleven years. The spirometric data included maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)]. Additionally, we measured serum biochemical indices and SBMA functional rating scale (SBMAFRS) for clinical analysis. Results: All three respiratory function tests showed a descending trend. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with the three pulmonary function tests. MIP and MEP correlated with creatine phosphokinase and creatinine levels, and FVC correlated with serum level of transaminases. Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in patients with SBMA. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

Keywords: spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (ASO); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule, combination therapy

Spinal muscular atrophy (SMA) is an orphan disease characterized by progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in the study. The median duration of drug treatment was over 20 months. Application of tSCS was performed during physical therapy for 20-40 minutes per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both types 2 and 3 SMA participants. The magnitude of functional changes was not associated with participants age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation in SMA.

Spinal muscular atrophy 5q (SMA) is the most common neuromuscular inherited disease in neonates which is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently established drugs can improve the motor functions of SMA infants when treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using real-time PCR assay with dried blood spots (DBS) was performed in Saint-Petersburg from January 2022 through November 2022. Here, 36,140 newborns were screened by GenomeX real-time PCR-based screening test, and three genotypes were determined. Homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns) and wild-type individuals (35,364 newborns) were identified. All four newborns screened positive for homozygous SMN1 deletion were confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined Saint-Petersburg spinal muscular atrophy incidence of 1 in 9,035 and SMA carrier frequency of 1 in 47. In conclusion, it can be summarized that providing both timely SMN1 information and confirmation along with SMN2 copy number as part of SMA newborn screening algorithm can significantly improve clinical follow-up, family members testing, and SMA patients' treatment.

Spinal muscular atrophy is a neuromuscular genetic condition associated with progressive muscle weakness and atrophy. Nusinersen is an antisense oligonucleotide therapy approved for the treatment of 5q spinal muscular atrophy in pediatric and adult patients. The objective of this clinical case series is to describe the efficacy and safety of nusinersen in treating spinal muscular atrophy in 20 pediatric and 18 adult patients across six treatment centers in Kuwait. Functional motor assessments (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module) were used to assess changes in motor function following nusinersen treatment. Safety assessment involved clinical monitoring of adverse events. The results demonstrate clinically meaningful or considerable improvement in motor performance for nearly all patients, lasting over 4 years in some cases. 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved clinically meaningful improvement in motor function following nusinersen treatment. Additionally, nusinersen was well-tolerated in both cohorts. These findings add to the growing body of evidence relating to the clinical efficacy and safety of nusinersen.

Spinal muscular atrophy is a neuromuscular disorder caused by mutationsin both copies of the survival motor neuron gene 1 (SMN1) which lead to reduction in the production of the SMN protein. Currently, there are several therapies that have been approved for SMA, with much more undergoing active research. While various biomarkers have been proposed for assessing the effectiveness of SMA treatment, a universally accepted one still hasnot been identified. This study aimed to investigate whether the number of gems in cell nuclei could serve as a potential biomarker for SMA. To gain insight into whether the number of gems in cell nuclei varies based on their SMN genotype and whether the increase in gems number is associated with therapeutic response, we utilized fibroblast cell cultures obtained from a patient with SMA type II and from healthy individual. We have discovered a remarkable difference in the number of gems found in the nuclei of these cells, specifically when counting gems per 100 nuclei. Then the SMA fibroblasts were treated with antisense oligonucleotides the beneficial effects in correcting the abnormal splicing of SMN2 exon 7 have been demonstrated. It was observed that there was a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The results obtained significantly correlate with an increase of full-length SMN transcripts share. Based on our findings, it is evident that the quantity of gems can be regarded as a reliable biomarker for SMA drugs development.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

The deficiency of Survival Motor Neuron (SMN) protein causes Spinal Muscular Atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in a SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma mem-brane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

Epicatechin has been described as a polyphenol compound that promotes skeletal muscle restructuring, by expressing muscle regulation factors, activation of satellite cells and modulation of the main pathways associated with catabolism. However, the literature shows contrasting results of therapeutic effects and treatment protocols. Thus, the aim of this systematic review was to analyze the current literature addressing the molecular mechanism and clinical protocol of epicatechin on skeletal muscular atrophy in humans and animals. A search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library databases. The qualitative analysis showed a prevalence of the inhibitory action of epicatechin in myostatin expression and atrogenes FOXO, MAFbx and MuRF1. Epicatechin showed positive effects on increased follistatin and on the activation of the myogenic regulatory factors (Myf5, MyoD and myogenin). In addition, the studies evidenced the impact of epicatechin on the mitochondrias' biosynthesis in muscle fibers, activation of the signaling pathway of AKT/mTOR protein synthesis, and improvement of skeletal musculature performance, particularly when associated with physical training. Epicatechin showed promising clinical applicability through beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization allowing to draw more specific conclusions on its therapeutic use.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is a debilitating neuromuscular disease characterized by progressive muscular weakness and neuronal degeneration, affecting 1-2 individuals per 100,000 globally. While SBMA is relatively rare, recent studies have shown a significantly higher prevalence of the disease within the indigenous population of Western Canada compared to the general population. The disease is caused by a pathogenic expansion of polyglutamine residues in the androgen receptor protein, which acts as a key transcriptional regulator for numerous genes. SBMA has no cure, and current treatments are primarily supportive and focused on symptom management. Recently, a form of precision medicine known as antisense therapy has gained traction as a promising therapeutic option for numerous neuromuscular diseases. Antisense therapy uses small synthetic oligonucleotides to confer therapeutic benefit by acting on pathogenic mRNA molecules, serving to either degrade pathogenic mRNA transcripts or helping to modulate splicing. Recent studies have explored the suitability of antisense therapy for the treatment of SBMA, primarily focused on antisense-mediated mRNA knockdown approaches. Advancements in understanding the pathogenesis of SBMA and the development of targeted therapies offer hope for improved quality of life for individuals affected by this debilitating condition. Continued research is essential to optimize these genetic approaches, ensuring their safety and efficacy.

Previous studies have found that individuals with limited motor capabilities due to acquired neurological injury (e.g., spinal cord injury and stroke) can make accurate action possibility judgements for neurologically healthy individuals. Previous studies have shown that people with limited motor capabilities may rely on previous motor experience (i.e., pre-injury) when making action possibility judgments for others. In the present study, we examined whether having severely limited previous motor experience from birth, as a consequence of spinal muscle atrophy (SMA), alters the action possibility judgments made for neurologically healthy individuals. Participants with SMA and Neurologically Healthy (NH) sex- and age-matched controls performed a perceptual-motor judgment task using the Fitts’s law paradigm (see Fitts, 1954). Participants observed apparent motion videos of reciprocal aiming movements with varying indices of difficulty (ID, see: Manson et al., 2014). For each movement, participants predicted the shortest movement time (MT) at which a neurologically healthy young adult could perform the task while maintaining accuracy. Between-group comparisons revealed that participants with SMA predicted significantly longer MTs compared to controls. Regression analyses revealed that predicted MTs of both NH and SMA participants exhibited a Fitts’s law relationship (i.e., the predicted MTs significantly increased as movement difficulty increased). A supplementary analysis on the SMA group revealed no differences in predicted MTs between the participants with some and no motor function as assessed by the SMA health index. Overall, these results provide evidence that participants with SMA who have limited or no motor experience may make more conservative action possibility judgments for others. Critically, our finding that the pattern of action possibility judgements (e.g., the slopes of the regression lines) were not different between SMA and NH groups provides evidence that limited previous motor experience may not completely impair action possibility judgements.

Caveolin is a structural protein within caveolae, which may be involved in transmembrane molecular transport and/or various intercellular interactions within cells. Specific mutations of caveolin-3 in muscle cells are well-known to cause a limb-girdle muscular dystrophy. Altered expression of the caveolin-3 has been also detected in Duchenne's muscular dystrophy, which may be a part of the pathological process leading to muscle weakness. Interestingly, it has been shown that the renovation of nitric oxide synthase (NOS) to the sarcolemma with muscular dystrophy could improve the muscle health, suggesting that NOS may be involved in the pathology of muscular dystrophy. Here, we summarize the notable function of caveolin and/or NOS in skeletal muscle cells, and would like to discuss about their involvement in the pathology as well as possible tactics for the innovative treatment of muscular dystrophies.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

This study aimed to identify whether gyrate atrophy of the choroid and retina (GACR) heterozygous individuals have possible clinical manifestations and to explore the potential pathogenic mechanism. In this retrospective study, we surveyed a two-generation pedigree of an individual diagnosed with GACR. Two family members underwent ophthalmological, hematologic, and genetic tests. An arginine-restricted diet with vitamin B6 supplementation was implemented; clinical assessments were repeated every 3 months during follow-up. Relative OAT mRNA expression was determined using real-time quantitative polymerase chain reaction. The 19-year-old compound heterozygous daughter (OAT: c.1186C>T; c.748C>T), had bilateral high myopia, posterior staphyloma, chorioretinal atrophy, macular abnormalities, and elevated hematologic ornithine. The 54-year-old heterozygous mother (OAT: c.1186C>T), presented with bilateral severe myopia, asymmetric posterior staphyloma, retina and choroidal capillary layer atrophy, retinal pigment epithelium abnormalities, and mildly elevated hematologic ornithine. Compared to normal individuals, the daughter and mother had 29% and 46% relative OAT mRNA expression, respectively (P<0.001). We believe that this is the first report of a carrier of one OAT variant allele with mild phenotypes, suggesting that family members should be aware of the possible involvement of autosomal recessive conditions. Additional data suggests nonsense mediated decay-initiated mRNA degradation may cause GACR.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Introduction Delayed intra-operative neuro-monitoring (IOM) events can be defined as loss of responses, after baseline traces were present upon completion of instrumentation and deformity correction. This study reports this subgroup of events, assesses their incidence and evaluates potential causative factors. Methods We reviewed 1881 consecutive patients who underwent spinal deformity correction between 2011 and 2021. Surgeries were performed using a standardised anaesthetic regimen and multimodal IOM protocol. Results 44 patients (2.4%) had an IOM event. 9 patients (6F:3M) had a true positive delayed event after posterior segmental pedicle screw instrumentation. Mean age was 12.5 (2-17) years with mean thoracic Cobb angle of 78° (51-94°). Mean estimated blood loss was 28%. Titanium beam shaped rods were utilised in 3 patients and 5.5mm titanium rods in 5 patients. Motor evoked potentials were lost on average 18 (10-30) minutes after completion of instrumentation. 7 patients had bilateral loss and 2 patients had unilateral loss of MEP traces. Sensory evoked potential amplitude was preserved in all cases. There was a transient latency shift in one patient. MEPs returned within 20 minutes of rod release. The rod was re-contoured to incorporate more scoliosis in 1 patient. 2 patients had beam rods exchanged to 5.5mm titanium rods. 6 patients had rod removal with retention of pedicle screws and staged completion of instrumentation at mean 5 (1-7) days later. No patients had a postoperative neurological deficit. Conclusion Delayed IOM loss represented 15% of all events. Increased cord tension and hypo-perfusion were considered likely mechanisms. Rod release restored MEPs in all cases. The timing of events emphasises the importance of continued monitoring for minimum 30 minutes after completion of spinal instrumentation or until wound closure.

Fatigue and dyspnea are the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. The purpose of the study was to comprehensively evaluate diaphragm muscle function in COVID-19 survivors, as well as investigate whether potential diaphragm dysfunction will contribute to physical functioning impairment. 46 patients qualified to pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while severity of dyspnea, aerobic capacity and amount of energy used by the body during physical activity were assessed by 6-minute walk test, mMRC scale and Metabolic Equivalent Task (MET), respectively. We identified 69.5% patients with diaphragm atrophy and 6.5% with diaphragm paralysis. Percentage of atrophy was not related to age, gender, BMI index, oxygen therapy use during COVID-19 infection course and severity of disease. Patients with presence of cough, fever and without loss of smell during COVID-19 course had a significantly greater values of diaphragm inspiratory thickness, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of person's exercise tolerance, such as distance in 6-minute walk test, saturation level, fatigue and exertion in Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID aftermath and can be viewed as a major contributing factor of prolonged functional impairments.

The objective of this study was to develop and evaluate artificial intelligence (AI) models for the detection and instance segmentation of vertebrae and spinal metastases in computer tomography (CT) scans. The models were trained on datasets consisting of patients with polytrauma and relatively undamaged spines, as well as patients diagnosed with spinal metastases. Our results indicate that the models achieved high performance in vertebra segmentation, with F-beta scores ranging from 0.88 to 0.96 across all vertebra classes. For spinal metastases, the model attained F-beta scores of 0.68 for lytic type and 0.57 for sclerotic type metastases. Additionally, the models demonstrated the capability to detect isolated metastatic nodes in other bones, highlighting their robustness and potential for broader clinical application. Despite these promising results, the study faced limitations including a relatively small and homogeneous dataset, variability in segmentation mask quality, and the need for real-world clinical validation. Future clinical trials are necessary to evaluate the practical utility and effectiveness of these AI models in improving patient outcomes. Our study emphasizes the potential of AI-assisted detection and segmentation models in enhancing diagnostic accuracy and efficiency in clinical practice.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder with a prevalence of approximately 1 in 3,500-5,000 males. DMD manifests as childhood-onset muscle degeneration, followed by loss of ambulation, cardiomyopathy, and death in early adulthood due to a lack of functional dystrophin protein. Out-of-frame mutations in the dystrophin gene are the most common underlying cause of DMD. Gene editing via the clustered regularly interspaced short palindromic repeats (CRISPR) system is a promising therapeutic for DMD, as it can permanently correct DMD mutations and thus restore the reading frame, allowing for the production of functional dystrophin. The specific mechanism of gene editing can vary based on a variety of factors such as the number of cuts generated by CRISPR, the presence of an exogenous DNA template, or the current cell cycle stage. CRISPR-mediated gene editing for DMD has been tested both in vitro and in vivo, with many of these studies discussed herein. Additionally, novel modifications to the CRISPR system such as base or prime editors allow for more precise gene editing. Despite recent advances, limitations remain including delivery efficiency, off-target mutagenesis, and long-term maintenance of dystrophin. Further studies focusing on safety and accuracy of the CRISPR system are necessary prior to clinical translation.

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyse the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week during 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week during 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

Sixteen crossbred rabbits (New Zealand white x Thai native breed) were randomly divided into two groups of eight to determine the effects of daily oral administration of crude extracts from the butterfly pea (Clitoria ternatea L.) from weaning (at 35 days) to slaughter (at 90 days). Effects on phagocytic activity of blood polymorphoneuclear leukocytes, serum biochemistry, meat quality, muscular lipid peroxidation, apparent digestibility, and gut histology were studied. The results revealed that the phagocytic function of circulating leukocytes (75 and 90 days) and alveolar macrophages (90 days) did not differ between the two groups. At slaughter, treated rabbits had lower blood urea nitrogen concentrations and higher liver weight than control rabbits (p < 0.05). After chilling at 4°C for 24 hours, lower meat pH and alteration of meat color (a brighter, less yellow, Hue angle and color saturation) were observed in the treated group (p < 0.05). Furthermore, lipid peroxidation (measured at 3, 5 and 7 storage days) in the meat of treated rabbits was lower than in controls (p < 0.05). Apparent digestibility (analyzed at 46 days for four days) revealed improved organic matter and ether extracts in the treated group (p < 0.05), whereas gut histology was unaffected. In conclusion, butterfly pea extract supplementation did not affect phagocytic function but led to a modification in meat color, delayed lipid peroxidation, and improved digestibility.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

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.

Objective: Interstitial fibrosis / tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm in estimating the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1/1/2012 to 1/3/2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features which were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients’ clinical data were used to produce ML-algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) have been included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. For IFTA ≥ 50%, AUCs in training cohort were 0.89, 0.84, 0.96, and in test cohort were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA>50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p < 0.0001; and WMH: 0.0004±0.0007; p < 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p < 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

Background: Injury of the spinal cord causes motor and sensory dysfunction, and pathological reflexes, leading to paraplegia or tetraplegia. The sequelae of traumatic spinal cord injury (SCI) is a significant burden and impact on healthcare systems. Despite constant progress in medicine, traumatic SCI still remains irreversible. Till now, no satisfying treatment that can enable neuronal regeneration and recovery of function at the damaged level has been found. Hundreds of experiments have been conducted on various possibilities of influencing spinal regeneration, some of them have yielded promising results, but unfortunately, the successes obtained in experimental animals have not translated into humans. Methods: This narrative review article presents the application of Extracorporeal Shock Wave Therapy (eSWT) in Spinal Cord Injury. The article has been divided into parts: 1. Use of extracorporeal Shock Wave Therapy for regeneration of the spinal cord after traumatic Spinal Cord Injury. 2. Application of extracorporeal Shock Wave Therapy in spasticity after Spinal Cord Injury. In both cases, the hypotheses of possible mechanisms of action will be described. Results and conclusions: A small number of clinical trials have demonstrated the potential of eSWT to influence the regeneration of the spine, as an innovative, safe, and cost-effective treatment option for patients with SCI. Some reports have shown that eSWT can improve spasticity, walking ability, urological function, quality of life, and independence in daily life.

Objective: This prospective study investigated the feasibility performing laparoscopic pelvic surgery in spinal anesthesia and analyzed their intraoperative side effects like pain and nausea and vomitus of 915 patients. Methods: Implementation and performance of laparoscopic surgery under local anes-thesia of 915 patients out of a total of 3212, who underwent laparoscopic pelvic surgery in spinal anesthesia, were analyzed in relation to BMI (Body Mass Index), obesity, pain during surgery and amount of intraperitoneal mmHg CO2 gas pressure and surgical complications. Results: BMI > 30, intraabdominal adhesions, increased duration of the operation, bleeding and increased intraperitoneal CO2 pressure were statistically significant as the main causes of pain during laparoscopic surgery in spinal anesthesia. Under-weight patients, on the other hand, had less pain when intra-abdominal pressure in-creased compared to those of normal weight. The appearance of pain, nausea and vomitus occurred in 10,3% and was easy to manage and treat. It did not affect the sur-geon's work and the course of the operation. Conclusion: In view of these observations, we are proposing spinal anesthesia for lap-aroscopic surgery as the first choice in those patients, who have no contraindications. In our knowledge this clinical study constitutes the largest clinical observations and dataset that applies spinal anesthesia in laparoscopic pelvic surgery.

MRI shows in-vivo the three archetypal patterns of CNS volume loss underlying progressive ataxias, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Freidreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, and repurposing therapies or enlargement of drugs indications in progressive ataxias.

Presenting a rare case of adult-onset mature cystic teratoma of the spinal cord in the thoracolumbar spinal cord in a 54-year-old male whose chief complaint was lower back pain radiating to both legs while other findings were normal. X-ray images of the thoracolumbar spine showed early degenerative changes and unfused posterior elements noted in lower sacral vertebral levels. Magnetic resonance images of the lumbar spine showed a well-defined non-enhancing intramedullary altered intensity lesion noted at the level of conus at the L1-L2 vertebral level. The resected tumour was histopathologically diagnosed as a mature cystic teratoma. The patient's symptoms improved following the surgery.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disorder most commonly caused by mutations disrupting the reading frame of the dystrophin (DMD) gene. DMD codes for dystrophin, which is critical for maintaining the integrity of muscle cell membranes. Without dystrophin, muscle cells receive heightened mechanical stress, becoming more susceptible to damage. An active body of research continues to explore therapeutic treatments for DMD as well as to further our understanding of the disease. These efforts rely on having reliable animal models that accurately recapitulate disease presentation in humans. While current animal models of DMD have served this purpose quite well, each comes with their own limitations. To help overcome this, clustered regularly interspaced short palindromic repeats (CRISPR)-based technology has been extremely useful in creating novel animal models for DMD. This review focuses on animal models developed for DMD that have been created using CRISPR, their advantages and disadvantages as well as their applications in the DMD field.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

Duchenne muscular dystrophy (DMD) is the most prevalent progressive muscular dystrophy, and the guidelines recommend the regular assessment of respiratory muscle function. This study aimed to assess the relationship between maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP) measurements and upright-supine spirometry parameters in children with DMD, predictability of upright-supine spirometry in terms of diaphragm involvement, and impact of nutrition on muscle strength. This prospective cross-sectional study examined patients with DMD by comparing upright and supine FVC, MIP, MEP, and SNIP measurements. Forty-four patients were included in the study. The mean patient age was 10.8±2.9 years. Twenty-five patients were ambulatory. A significant decrease in FVC, FEV1, and FEF25-75 values was detected in the supine position in both ambulatory and nonambulatory patients (p<0.05). All patients had low MIP, MEP, and SNIP measurements (less than 60 cm H2O). MIP, MEP, and SNIP values were significantly lower in patients with malnutrition than in those without (p<0.05). To accurately assess respiratory muscle strength, supine FVC should be combined with upright FVC, MIP, MEP, and SNIP measurements. It is crucial to regularly screen patients for malnutrition, as this can significantly affect respiratory muscle function during pulmonology follow-up.

A progressive and chronic neurological condition called MSA (Multiple System Atrophy) is characterized clinically by varying degrees of dysautonomia, cerebellar ataxia, and parkinsonism. The concept of mitochondrial dysregulation in MSA is one perspective in handling this neurodegenerative disease. Damage to functional mitochondria is driven by the presence of ɑ-Synuclein-induced mitochondrial localization. The goal of MSA treatment up until now has been to reduce symptoms. One of the innovations in the treatment of MSA could be the novel idea based on mitochondrial reprogramming pathways. Mitochondrial reprogramming can be done in various ways in which the use of hydrogen, magnesium and low-dose hydrogen peroxide.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

The aim of this report is to evaluate the segmental rib index (RI) from T1-T12 spinal level in mild and moderate idiopathic scoliosis (IS) curves of thoracic, thoracolumbar and lumbar type by gender. The relationship of segmental RI to the frontal plane radiological deformity presented as the Cobb angle and to the posterior truncal surface deformity presented as the scoliometric readings of Angle of Trunk Rotation (ATR) in these patients is also assessed. Any statistical significant rela-tionship of these parameters would be very important for biomechanical relations of the rib cage (RC) deformity presented as the rib hump deformity (RHD) and the deformity in the spine and it would thus provide valuable information about scoliogeny. The segmental rib index (RI) is presented in 83 boys and girls with mild and moderate IS. The measurements include the scoliometric readings for truncal asymmetry (TA), the Cobb angle assessment and the segmental RI from T1-T12. The statistical package SPSS 23 was used for statistical analysis. The TA is documented and the Cobb angle is presented by gender and curve type. The segmental RI of thoracic, thoracolumbar and lumbar curves are presented for the first time. The correlations of the segmental RI to surface deformity presented as the rib hump deformity (RHD) in all IS patients and particularly in thoracic curves, to Cobb angle by gender and age and the comparison of the segmental RI index of asymmetric but not scoliotic children to the scoliotic peers by curve (in thoracic, thoracolumbar, lumbar curves) in boys and girls are presented. The findings emphasize the significant protagonistic role of the thoracic asymmetry in relation to the spinal deformity mainly in girls for the thoracic and in boys for the thoracolumbar curves. The cut-off point of age of the examined scoliotics is 14 years, that is when the RI shows stronger correlation with the spinal deformity, namely when the thoracic deformity is decisively effective to the developing thoracic spinal deformity, in terms of Cobb angle. In summary, the results of this study provide aetiological implications for IS, as far as the role of thorax is con-cerned.

In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in particular spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and predominantly spinal cord injury (SCI) with occasional relations to stroke. Especially the changes in SCI (and stroke) depend on the cause, site and extent of the afflicted damage and are therefore multifarious. At the end, we will briefly summarize results indicating that operant, classical and instrumental conditioning can be used to produce plastic changes in healthy people, with potentials for applications to patients with spinal cord injury. In order not to overload the article, we will not delve deeply into sub-cellular processes.

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy, characterized by progressive and asymmetric muscle atrophy, primarily affecting muscles of the face, shoulder girdle, and upper arms before affecting muscles of the lower extremities with age and greater disease severity. FSHD is a disabling condition, and patients may also present with various extramuscular symptoms. FSHD is caused by the aberrant expression of double homeobox 4 (DUX4) in adult skeletal muscle, arising from compromised epigenetic repression of the D4Z4 array. DUX4 encodes the DUX4 protein, a transcription factor that activates myotoxic gene programs to produce the FSHD pathology. Therefore, sequence-specific oligonucleotides aimed at reducing DUX4 levels in patients is a compelling therapeutic approach, and one that has received considerable research interest over the last decade. This review aims to describe the current preclinical landscape of oligonucleotide therapies for FSHD. This includes outlining the mechanism of action of each therapy and summarizing the preclinical results obtained regarding their efficacy in cellular and/or murine disease models. The scope of this review is limited to oligonucleotide-based therapies that inhibit the DUX4 gene, mRNA, or protein in a way that does not involve gene editing.

Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/3500 boys globally, characterized by progressive muscle breakdown and eventual death with an average lifespan in the mid-late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.

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.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysiological changes after injury. While low dose nicotine (1µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom double-transgenic mouse, we studied the effect of nicotine (0.5-10µM) on locomotor networks in-vitro. Nicotine 10µM induced motoneuron depolarization, suppressed monosynaptic reflexes, and decreased fictive locomotion in rat spinal cord. Delayed fall in neuronal numbers (including motoneurons) of central and ventral regions emerged without loss of dorsal neurons. Conversely, nicotine (0.5-1µM) preserved neurons throughout the spinal cord and strongly activated the Wnt1 signaling pathway. High-dose nicotine enhanced expression of S100 and GFAP in astrocytes suggesting their response to stress. Excitotoxicity induced by kainate was contrasted by nicotine (10µM) in the dorsal area and persisted in central and ventral regions with no change basal Wnt signaling. When combining nicotine with kainate, the activation of Wnt1 was reduced compared to kainate/sham. The present results suggest that high dose nicotine was neurotoxic to central and ventral spinal neurons as the neuroprotective role of Wnt signaling became attenuated. This also corroborates the risk of cigarette smoking for the foetus/newborn since tobacco contains nicotine.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

The increasing prevalence of spinal disorders and the subsequent rise in spinal fusion surgeries stress the necessity for optimizing spinal fusion cages, crucial for stabilizing the spine and supporting osseointegration. Despite the widespread attempts at material modifications and surface enhancements to improve these devices, failure rates and complications remain significant. This research explores an imaginitive approach to enhancing spinal fusion cages through the application of geometric tiling designs, a method scarcely employed . The study systematically investigates the potential of triangular, diamond, and hexagonal tiling patterns to improve the structural integrity and capability for osseointegration of spinal fusion cages. Through a finite element analysis simulation, each design's ability to withstand multi-directional loads and effectively distribute stress was tested under simulated conditions that mimic the complexities of spinal motion. Preliminary findings in fields of engineering indicate that geometric tiling can significantly enhance the load-bearing capabilities and stress distribution of spinal fusion cages, potentially reducing the likelihood of implant subsidence and failure. The triangular and hexagonal designs, in particular, demonstrate superior performance in maintaining structural stability under axial and anterior compressive forces compared to traditional cage designs. This research opens a new pathway for the development of more durable and efficient spinal fusion cages. By leveraging the structural advantages of geometric tiling, future spinal implants could achieve better clinical outcomes, leading to improved patient recovery and reduced rates of complications.

Spinal Cord Injury in children can be a devastating condition in children with profound implications for their overall health and quality of life. In this review we aim to provide a concise overview of the key aspects associated with SCI in pediatric population. Firstly, we discuss the etiology and epidemiology of SCI in children, highlighting the diverse range of causes. We explore the unique anatomical and physiological characteristics of the developing spinal cord that contribute to the specific challenges faced by pediatric patients. Next, we delve into the clinical presentation and diagnostic methods, emphasizing the importance of prompt and accurate diagnosis to facilitate appropriate interventions. Furthermore, we approach the multidisciplinary management of pediatric SCI, encompassing acute medical care, surgical interventions, and ongoing supportive therapies. Finally, we explore emerging research and innovative therapies in the field and we emphasize the need for continued advancements in understanding and treating SCI in children to improve their functional independence and overall quality of life.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein which leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.

While some research supports utilizing plain radiography for measuring biomechanical alignment of the spine for prognosis and treatment, there are contrasting viewpoints regarding both the value and utilization of these procedures in conservative care. Evaluation of both conservative and non-conservative approaches to spinal care revealed vast differences in radiographic utilization and interpretation between orthopedic surgeons, primary care physicians, chiropractic physicians, and physical therapists, which may account for the different viewpoints and rationale in the literature. A research summary is provided regarding the various methods of spinal analysis utilized by these professions to help determine if there is any unique diagnostic or prognostic value associated with radiographic utilization that could assist in advancing conservative spinal assessment and treatment. Understanding any unique value provided through biomechanical assessment utilizing plain radiography of the spine established in the literature may help chiropractic physicians determine the appropriate use of radiographic procedures in clinical practice and how to coordinate efforts with other conservative and non-conservative professions to improve spinal healthcare.

Introduction: The COVID-19 pandemic challenged people with spinal cord injury (SCI) regarding a variety of mental and physical issues. New challenges may arise as the effects of the pandemic continue. The objective of the present study was to explore the social participation of Canadians with SCI during the second wave of COVID-19. Methods: Participants with SCI from two Canadian provinces (Quebec and British Columbia) were interviewed. Results: Eighteen participants completed interviews. Facilitators of social participation remain similar since the first wave of COVID-19, such as the use of technology, help received by relatives and the use of delivery services to obtain groceries and other essentials. Obstacles to mobility due to winter conditions and lack of considerations related to COVID-19 public health measures specific to wheelchair users were also discussed by participants. Conclusions: People with SCI perceived participation restrictions, little changes in life habits, and uncertainty about the future during the second wave of COVID-19. The unique living conditions of people with SCI, ability to adapt life habits, and the lived experiences of people with SCI may have contributed to an overall resilience during the pandemic. Adaptive families, social contacts and technology made a difference during the pandemic.

Exoskeleton technology has been shown to be useful for individuals with spinal cord injury (SCI), potentially facilitating their recovery of motor function and social reintegration. However, studies on the safety and usability of exoskeletons are limited. This study aimed to design a powered exoskeleton for SCI and evaluate its safety and usability. Ten healthy adults participated in this study. The prototype exoskeleton featured an adjustable frame, computer-controlled hip and knee joint actuators, and a gait-trigger sensor. The experimental actions included walking, standing, and sitting, with and without the prototype. Safety outcomes included adverse events, vital signs, numerical rating scale (NRS) scores for pain, discomfort, and fatigue, and prototype-human body clearance. Usability outcomes included donning and doffing times, subjective ratings, gait speed, stride length, and kinematic parameters of hip and knee joint angles. Safety outcomes showed no serious adverse events, stable vital signs, minimal NRS scores, and acceptable clearance. Usability outcomes showed high efficiency and received positive ratings. Kinematic parameters showed significant positive correlations between normal walking and walking with the prototype for both hip and knee joint angles, confirming its effectiveness in assisting walking. However, further device improvements and gait parameter tuning are necessary for future clinical application.

This study proposes a cephalometric analysis that can be used for biomechanical simulation by considering the important and complex relationship between craniofacial morphology and masseter muscle (MM) size and inclination and by including muscle values. The MM line of action drawn between the Gonion (Go) and Orbital (Or) point relative to dental and skeletal references (occlusal and Frankfort planes) were analyzed. A total of 510 pre-treatment lateral cephalometric tracings (217 males, 293 females, 6-50 years) and lateral Bolton standard tracings (6-18 years) were analyzed. The study examined the following: a) skeletal-cutaneous class (linear distance in mm between the projections of points A' and B' on the occlusal plane), b) the angle between the perpendicular line to the occlusal plane and the Go-Or line at the molar occlusal point, and c) the angle between the Go-Or line and the Frankfort plane. The skeletal classes of the patients ranged from -14.5 to 15.5 mm and did not differ by sex or age; the angle between the Go-Or line and the normal to the occlusal plane averaged 39° (range 15° to 53°) and decreased with age, while the angle between the Go-Or line and the Frankfort plane averaged 42° (range 30° to 54°), increased in older patients. No effect of gender was observed. The two angles were also significantly correlated with each other, but not with sagittal jaw discrepancy. Similar results were obtained with Bolton tracings; the positional relationship of the Go-Or line to the teeth and skeletal landmarks is partially consistent with the literature. The present cephalometric analysis can be usefully used to estimate the mechanical advantage of MM in biomechanical simulations of masticatory muscle performance.

Background. Sarcopenia and spinal cord injury (SCI) often coexist, but little is known about the associations of these two pathologies. This study aimed to assess the impact of SCI on muscle and bone mass and the correlations between clinical characteristics of SCI patients and sarcopenia. Methods: 136 patients diagnosed with SCI admitted to rehabilitation hospital were included in the study. The type and severity of injury (AIS), the level of spasticity (MAS), bone mineral density and Appendicular Lean Muscle Mass (ALM) were assessed. Sarcopenia was diagnosed according to the recommended EWGSOP2 cut-off points for ALM. Results: There was a statistically significant association between the ALM value and the gender, 75% of women developing sarcopenia. Among men, 42.9% had sarcopenia. Over 55% of AIS Grades A and B cases had sarcopenia. Mean age of sarcopenic patients was 35.8 years and they had multiple comorbidities. 51.6% of the patients with osteoporosis had sarcopenia. 69.7% of MAS level 0 cases had sarcopenia, while this was diagnosed in about 40% of patients with MAS levels 1-4. Conclusions: Gender, type of injury, presence of multiple comorbidities and age were directly associated with sarcopenia, while surprisingly, spasticity level and the presence of immobilization osteoporosis were not.

Loss of muscle mass and strength are progressing with aging. Exercise is a beneficial method to prevent physical disfunction and habitual exercise improve the muscle quality. Therefore, we evaluated the effects of a long-term habitual exercise on the senescence-accelerated mice prone8 (SAMP8). 27wk SAMP8 were used in this study. Mice were classified into 28 (28w) and 44 weeks old. The 44-week group was divided into the sedentary group (44w) and a group exercising for 16 weeks (44w+Ex). The 44w+Ex performed habitual exercise from 28 to 44 weeks. Additionally, grip strength tests were performed with mice aged 28 and 44 weeks. Mice were dissected and collected muscle samples and measured muscle weight at 44w. Gastrocnemius was decreased in 44w but were unchanged in 44w+Ex. Grip strength in 44w was lower trend, but there was no change in 44w+Ex. The phosphorylation levels of Akt and p70S6K as a protein synthesis marker were decreased in 44w. Cytochrome c oxidase subunit IV(COXIV) mRNA and protein levels decreased in 44w. These results suggested that long-term habitual exercise attenuated muscle mass and strength decline through improving muscle protein synthesis and mitochondrial function. In conclusion, long-term habitual exercise attenuated muscle mass and strength decline.

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

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.

Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

(1) Background: This study aims to investigate differences in the perspectives of exercise intensity for resistance exercise of healthcare professionals (HCPs) and adults living with spinal cord injury (SCI) in Asian countries. Also, it verifies the appropriateness of the conventional indicators for resistance exercise intensity in an Asian context; (2) Methods: 121 certified HCPs and 107 adults with SCI participated in a survey conducted in Indonesian, Japanese, Korean and Thai languages. The survey asked what principles are important for prescribing resistance exercise, and if ‘moderate’ and ‘vigorous’ were appropriate terms for indicating an intensity level. Perspective differences were examined between both groups and, further, between countries from a psychosocial perspective; (3) Results: Of the HCPs, 92% perceived that resistance exercise intensity was far more important than frequency, time or type of exercise while frequency (61%) followed by intensity (58%) was perceived as important by respondents with SCI. Only Japanese respondents with SCI agreed with HCP’s perception of intensity. Both HCPs and respondents with SCI showed unfavorable responses on the usage of ‘moderate’ and ‘vigorous’ for describing resistance exercise intensity, especially Japanese HCP and respondents with SCI from Indonesia; (4) Conclusion: Our findings suggest that non-HCPs must improve their perceptions of exercise intensity. Findings also suggest the need for more explicit and user-friendly terms or expressions indicating the level of intensity in a local (Asian) context.

The severest form of muscular dystrophy (MD) termed Duchenne MD (DMD) remains to this day an incurable disease, hence the continued effort to further develop supportive therapies. Perturbation of autophagy, a degradative yet protective mechanism activated when tissues face severe and persistent stress, is critically involved in DMD, consequently, treatments harnessing autophagic capacities represent an amenable therapeutic strategy. We studied the effects of the protective osmolyte ectoine in the standard mouse model of DMD, the MDX, zooming in on the autophagy-related proteome. From birth, mice were treated with ectoine in the drinking water (150mg/kg) or through daily intraperitoneal injection (177mg/kg) until 5 weeks old. Hind limb muscles were dissected, performing western blotting for protein quantification and immunofluorescence to investigate tissue distribution. We report significant alterations of total levels of autophagy related 5 (ATG5), Ser366 phosphorylated sequestosome 1 (SQSTM1) and heat shock protein 70 (HSP70), and of activated microtubule-associated protein 1A/1B-light chain 3 (LC3 II) in mitochondrial fractions. Ectoine tends to restore the shifted balance between LC3 II and SQSTM1 levels observed in MDX muscle, and LC3 II upregulation was most pronounced on muscle fibers of MDX treated with ectoine in the drinking water. Findings from this explorative study support a possible beneficial effect of ectoine on the autophagic deficit in the MDX, which warrants its further exploration as a therapeutic supplement for DMD.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

In our country, the aging society is rapidly progressing, with an increase in patients with chronic kidney disease (CKD) and those undergoing dialysis, coupled with the aging of the population. As a result, the number of individuals with cognitive impairment (CI) is rising, and addressing this issue has become an urgent problem. One characteristic of dementia in CKD patients is the high frequency of vascular dementia, making the prevention through the management of classical risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, etc., associated with atherosclerosis and arteriosclerosis. Other effective measures, including the use of renin-angiotensin system inhibitors, addressing anemia, exercise therapy, and lifestyle improvements, have been reported. Incidence and progression of CI may also be influenced by the type of dialysis or kidney replacement therapy, with reports suggesting that long-duration dialysis, low-temperature hemodialysis, peritoneal dialysis, and kidney transplantation (KTx) can have a possible preferable effect on preserving cognitive function.

The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach could not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies including electrical stimulation, training, pharmacological treatments, or cell implantation that resulted in improvements in locomotor behaviour, rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers to classify these populations.

The length of time it takes to experimentally make one-sided choppers, as found in the fossil record, bears a linear relationship to the knapping process of fabricating them. In addition, this temporal frame appears to be related to human heart rates measured as beats per minute, which act as a physiological metronome. We achieved these observations assuming that any paleolithic one-sided chopper has the information needed to estimate quantitatively the number of strikes on it. The experimental data allow us to establish the total timing needed for the standard fabricating of any one-sided chopper. We discuss issues derived from these experimental results, showing the evolution of human neurological abilities from 2.4 million years ago to the Modern period through the duration of time needed for making one chopper to that needed to play a 19th-century music score on a piano. Given that the neuronal and physiological distance between both actions differs by a factor of 6, we propose the concept of “technome” to measure human evolution by using methodological homogeneous metrics applied to these two human technologic objects, the chopper and the piano.

The purpose of the present study was to investigate the effects of psychological pressure on corticospinal excitability, the spinal reflex, lower limb muscular activity, and reaction times during a task involving dominant leg movements. Ten healthy participants performed a simple reaction time task by raising the heel of their dominant foot from a switch. After 20 practice trials, participants performed 20 non-pressure and 20 pressure trials in a counterbalanced order. Stress responses were successfully induced, as indexed by significant increases in state anxiety, mental effort, and heart rates under pressure. Significant increases in motor evoked potential (MEP) amplitude of the tibialis anterior muscle (TA) occurred under pressure. In terms of task-related EMG amplitude, the co-contraction rate between the soleus (SOL) and TA muscles significantly increased along with SOL and TA EMG amplitudes under pressure. Hoffmann reflexes for SOL and reaction times did not change under pressure. These results indicate that corticospinal excitability and leg muscle-related EMG activity increase homogeneously during lower limb movements that are performed under psychological pressure.

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macro-phages and reactive M1 microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in a the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlight the time-dependent transformation of reactive mi-croglia (M1) and astrocytes (A1) into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide sug-gestions on how to increase functional outcome after SCI and discuss key therapeutic approaches.

IgA nephropathy (IgAN) is one of the most common forms of glomerular disease. It is diagnosed by the dominant or co-dominant IgA deposition in the mesangial region by histopathological examination of kidney biopsy. Kidney biopsy has its own complication and not performed frequently. microRNA (miRNA) is a small RNA, which plays an important role at the post transcriptional level by downregulating mRNAs. We have tried to establish a miRNA based biomarker for IgAN. We quantified miR-148b and let-7b from plasma in IgAN patients and healthy controls. Logistic regression models and receiver operating curve analysis used to analyze the miRNAs quantity and Oxford MEST-C scoring parameters (M- Mesangial hypercellularity, E- Endocapillary hypercellularity, S- Segmental glomerulosclerosis, T- Tubular atrophy/Interstitial fibrosis, C- Crescents). miR-148b and let-7b levels in IgAN were found to be higher by 2.9 and 5.48 times than the healthy controls, respectively. let-7b was positively correlated with complement C3 levels. Similarly, miR-148b was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with S, T, and blood pressure (BP). The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) for miR-148b against T were 0.87, 0.77, and 0.85, respectively. The threshold value of miR-148b concentration was found to be 8479 to differentiate the severe condition of IgAN. Furthermore, the decrease in miR-148b concentration at a threshold point indicated the progression of the severity of the IgAN. It can also be used to predict the IgAN at an earlier stage.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. Much of what we know about sarcopenia derive from studies on small rodents which serve as models for the human condition. Here we used outbred male rats to study the natural history of sarcopenia with the aim to compare behavioral motor deficits with degree of muscle wasting and to find processes underlying the preclinical phase of sarcopenia. Selected metrics were validated in female rats. We used the soleus muscle because of its long duty cycles in everyday life and significance for postural control. The results show that gait and coordination remain intact through middle age (12-18 months; 40%-60% of median lifespan) when muscle mass relative to body weight is largely maintained. The muscle, however, show multiple signs of remodeling with a shift in myofiber-type composition towards type I, increased number of hybrid fibers and fibers expressing embryonic myosin. In parallel with the shift in fiber type prevalence, fiber type clustering increased. The latter combined with a transcriptional upregulation of nicotinic acetylcholine receptor subunit  (CHRN ), NCAM and Myogenin (MYOG) suggests a remodeling driven by myofiber denervation. Additional stigmata were increased number of central nuclei, transcriptional upregulation of Smad3, FBXO32, and MuRF1mRNAs; unaltered density of satellite cells (SC) and Catenin mRNA. In early (25-month-old) and advanced (30-month-old) aging, gait and coordination deteriorate as loss of muscle mass progresses. In late middle age and early aging because of a type II atrophy (>50%), followed by type I atrophy (>50%). Number of myofiber did not correlate with this process. At advance age, the atrophy is accompanied by a decrease in SC and Catenin mRNA while several transcripts upregulated earlier-on were downregulated. In contrast, glial-derived nerve growth factor (GDNF) mRNA abundance peaked at endpoint. We conclude that sarcopenia in the rat as in humans, has a long preclinical phase where the muscle undergoes extensive remodeling to preserve muscle mass and function. The data supports the notion that myofiber denervation is the instigating mechanism, initially affecting large type II motor units (MUs) and at more advanced stage also the smaller type I MUs.

Background/Objectives: High-intensity anaerobic physical training frequently results in muscle damage among boxers and kickboxers, which can impede performance and recovery. Vibrational therapy (VT) and passive rest (PR) have been employed as methods to enhance muscular recovery and performance. This study evaluates the effectiveness of these two recovery methods on upper limb muscle strength and lactate levels in plasma after high-intensity exertion. Methods: Eighteen elite boxers and kickboxers, aged 19-32 years, underwent tests employing VT and PR as recovery methods in a controlled, crossover study. Muscle performance was assessed via isokinetic dynamometry, and lactate levels were measured pre-exercise, post-exercise, and post-recovery. The study adhered to the Declaration of Helsinki guidelines and was approved by the relevant bioethics committee. Results: The results showed that VT led to a faster recruitment of muscle fibers and improved muscle endurance as indicated by decreased fatigue work indices compared to PR. However, no significant differences were observed in peak torque or lactate levels between the two recovery methods. The VT group exhibited quicker recovery times in torque generation and better performance in fatigue resistance. Conclusions: VT appears to provide superior muscular recovery compared to PR following intense anaerobic effort, particularly in terms of muscle strength endurance and activation speed. These findings support the potential of VT in sports recovery protocols, although similar lactate response suggests that metabolic recovery rates are not significantly affected.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

Background This study aimed to examine the acute effects of different pre-ST strategies on muscular performance and blood pressure (BP) responses in recreationally strength-trained women. Methods: Twelve overweight women with normal-to-elevated BP were recruited and performed six exper-imental protocols in a randomized order: 1) control protocol (CC) – BP assessed without exercises performed, 2) strength training (ST), 3) foam rolling warm-up followed by strength training (FR+ST), 4) specific warm-up followed by strength training (SW+ST), 5) aerobic exercise followed by strength training (AE+ST), and 6) stretching exercises followed by strength training (SE+ST). Strength training consisted of three sets at 80% of 10RM with a self-suggested rest interval between sets for bench press, back squat, bench press 45º, front squat, lat pull-down, leg press, shoulder press, and leg extension. Results: All experimental protocol had a lower total training volume, fa-tigue index, and repetitions performance in relation to ST (p

The purpose of this qualitative study was to describe parent perceptions of the home exercise pro-gram (HEP) for their infant with congenital muscular torticollis (CMT), and how these perceptions evolved over a physical therapy (PT) plan of care. Twelve participants were recruited from a pediatric PT clinic, and nine completed interviews at three time points. Qualitative description and an iterative approach for thematic analysis of 27 interviews yielded three themes that corresponded to the research questions. The participants’ responses were categorized into three main themes: 1) parents’ perceptions of three key exercises within the HEP; 2) internal and external sources of stress; and 3) sources of empowerment and disempowerment. Regarding the HEP, parents articulated common sentiments for three frequently prescribed exercises for the management of CMT: 1) Tummy time was the fast favorite, 2) ipsilateral cervical rotation was perceived as stressful, and 3) contralateral cervical lateral flexion felt uncomfortable. Additionally, participants disclosed internal and external sources of stress (guilt, uncertainty, and the demands of returning to work) and sources of disempowerment (inconsistent messaging from providers, feeling overwhelmed) and empowerment (being able to see the bigger picture and clear communication and education about the diagnosis) with respect to managing their infant’s CMT. These themes provide insight into the evolution of parent perceptions over a PT plan of care for CMT. Participants’ insights suggest a need for consistent messaging regarding the diagnosis and evidence-based management of CMT, addressing parent stress, and modifying how exercises are taught. This study contributes updated research on parents’ experience with physical therapy and the HEP for their infant’s CMT.

Duchenne muscular dystrophy (DMD) is a yet incurable rare genetic disease that affects the skeletal and cardiac muscles, leading to progressive muscle wasting and premature death. DMD is caused by the lack of dystrophin, a muscle protein essential for the biochemical support and integrity of muscle fibers. Gene replacement strategies for Duchenne muscular dystrophy (DMD) employing the adeno-associated virus (AAV) face the challenge imposed by the limited packaging capacity of AAV, only allowing the accommodation of a short version of dystrophin (µDys) that is still far removed from correcting human disease. The need to develop strategies leading to the expression of a best performing dystrophin variant led to only few studies reporting on the use of dual vectors, but none reported on a method to assess in vivo transgene reconstitution efficiency, the degree of which directly affects the use of safe AAV dosing. We report here on the generation of a dual AAV vector approach for the expression of a larger dystrophin version (quasidystrophin) based on homologous recombination, and the development of a methodology employing a strategic droplet digital PCR design, to determine the recombination efficiency as well as the occurrence of unwanted concatemerization events or aberrant expression from the single vectors. We demonstrated that, upon systemic delivery in the dystrophic DBA2mdx mice, our dual AAV approach led to high transgene reconstitution efficiency and negligible ITR-dependent concatemerization, with consequent remarkable protein restoration in muscles and improvement of muscle pathology. This evidence supports the suitability of our system for gene therapy application and the potential of this methodology to assess and improve the feasibility for therapeutic translation of multiple vector approaches

Introduction:In this study we evaluated the connivance of oxidative and antioxidative parameters in the pathogenesis of spinal cord injury (SCI). Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress may play a significant role in the pathophysiology of SCI. Furthermore, there is little information available in scientific literature about oxidative and antioxidative parameters in SCI patients. Methods:Oxidative stress was determined by measuring the levels of Lipid Peroxides (LPO) and Protein carbonyl in plasma and antioxidative parameters like Glutathione Reductase (GR), catalase and Glutathione peroxidase (GPx) in lysate in 40 SCI patients and 40 healthy subjects without SCI. However, pain was measured by McGill pain questionnaire. Results: Concentrations of catalase (p<0.01), GR (p<0.01) and GPx (p<0.01) were significantly lower in patients with SCI than in controls, and levels of oxidative stress parameters, LPO (p<0.01), Protein carbonyl (p<0.01) were significantly higher in patients than in controls. A significant positive correlation was found between LPO and pain score among SCI patients group. Furthermore, a significant positive correlation was also found between Protein carbonyl and pain score among SCI patients group than in control group. Conclusion: The present results indicate that SCI patients are exposed to oxidative stress and this escalated oxidative stress may play a role in the etiopathogenesis of the disease. Moreover, our results also show that increased oxidative stress parameters are more strongly amalgamated with pain in SCI patients.

As an uncommon cause of spinal cord infarction, anterior spinal cord syndrome can manifest with motor paralysis, loss of pain, and temperature sensation distal to the site of the lesion. The main pathogenesis of this syndrome is the disruption of blood flow in the anterior spinal artery. Mortality and morbidity differ with the etiology of the syndrome. So knowing the etiology of blood flow disruption is essential for patient management. This review article highlights the important clinical manifestation of Anterior spinal artery syndrome. Also describes etiology, pathogenesis, diagnosis, prognosis, possible management, and complications.

: Medial temporal lobe atrophy (MTA) remains an important imaging biomarker in brain magnetic resonance imaging (MRI) for diagnosing and evaluating Alzheimer's disease (AD). We compared the detection performance for determining significant MTA and the correlation with Scheltens' scale between two automatic volumetry software, NeuroQuant® and Aqua®, in non-AD and AD groups. Overall, 127 (non-AD, 54; AD, 73) individuals who underwent three-dimensional T1-weighted volumetric MRI in our hospital between January and August 2011 were enrolled and retrospectively analyzed using NeuroQuant® and Aqua®. The accuracy, sensitivity, and specificity for detecting significant MTA and the correlation for Scheltens' scale with the mean hippocampal volume of each software were evaluated. The study sample’s mean age was 78 (range, 59–97) years. Regarding accuracy and specificity, Aqua® was non-inferior to NeuroQuant®. Aqua® had significantly higher overall specificity than NeuroQuant® for detecting significant MTA. Additionally, the calculated mean hippocampal volume of Aqua® was more correlated with Scheltens' scale (Kendall's τ, - 0.48) than that of NeuroQuant® (Kendall's τ, - 0.20). The accuracy and specificity of Aqua® in detecting MTA are not inferior to those of NeuroQuant®. Additionally, Aqua® has a stronger correlation of mean hippocampal volume with Scheltens' scale than NeuroQuant®.

Skeletal muscle atrophy is one of the major side effects of high dose or sustained usage of glucocorticoids. Pyroptosis is a novel form of pro-inflammatory programmed cell death that may contribute to skeletal muscle injury. Trimetazidine, a well-known anti-anginal agent, can also improve skeletal muscle performance both in human and mice. We here showed that dexamethasone induced atrophy, evidenced by the increase of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) expression , and the decrease of myotube diameter in C2C12 myotubes. Dexamethasone also induced pyroptosis, indicated by upregulated pyroptosis-related protein NLRP3, Caspase-1 and GSDMD. Knockdown of NLRP3 or GSDMD attenuated dexamethasone-induced myotube pyroptosis and atrophy. Trimetazidine administration ameliorated dexamethasone-induced muscle atrophy both in vivo and in vitro. Moreover, trimetazidine improved exercise tolerance, as evidenced by increased running distance and running time, as well as increased skeletal muscle mass in dexamethasone-treated mice. Mechanically, trimetazidine could reverse dexamethasone-induced activation of pyroptosis both in C2C12 myotubes and in mice. Taken together, our present study demonstrated that NLRP3/GSDMD pathway-mediated pyroptosis was involved in dexamethasone-induced skeletal muscle atrophy. Trimetazidine could partially alleviate dexamethasone-induced skeletal muscle atrophy, and increase the diameter of C2C12 myotubes via inhibiting pyroptosis. Thus, trimetazidine might be a potential therapeutic compound for the prevention of muscle atrophy in glucocorticoid-treated patients.

Background/Objectives: Traditional neurosurgical training involves a steep learning curve. The introduction of advanced simulation technologies, such as virtual reality (VR), provides an alternative method for skill acquisition, allowing for repeated practice and objective assessment. This study focuses on evaluating the learning curve associated with lumbar pedicle Kirschner wire insertion using a virtual fluoroscopic simulator among neurosurgical residents. Methods: Eighteen neurosurgery residents and two interns participated in this study. Participants’ initial skill levels were assessed through a questionnaire. Performance metrics, including insertion accuracy, time, and the number of virtual X-ray scans, were recorded across multiple attempts until a “practical learning plateau” was reached. Statistical analyses were conducted to model learning curves, assess the correlation between pre-training experience and performance. Results: The average number of attempts required to stabilize performance was 5.61. Learning rates varied, with some residents showing rapid improvement while others progressed more slowly. Higher accuracy in wire placement correlated with reduced usage on X-rays over time. However, experienced residents did not necessarily learn faster, indicating potential challenges in adapting to new simulation-based methods. Post-training feedback highlighted the simulator’s utility in increasing confidence and skill levels, although some limitations in anatomical accuracy were noted. Conclusions: This study demonstrates the potential of virtual simulation to enhance neurosurgical training by providing a controlled environment for repeated practice and objective feedback. Simulation-based training can effectively complement traditional methods, though individualized approaches may be necessary to accommodate varying learning rates among residents. Further refinement of simulation tools and their integration into standard training curricula are recommended.

Artificial intelligence has garnered significant attention in recent years as a rapidly advancing field of computer technology. With the continual advancement of computer hardware, deep learning has made breakthrough developments within the realm of artificial intelligence. Over the past few years, applying deep learning architecture in medicine and Industrial anomaly inspection has significantly contributed to solving numerous challenges related to efficiency and accuracy. Despite excellent results in radiological, pathological, endoscopic, ultrasonic, and biochemical examinations, this paper utilizes deep learning combined with image processing to identify spinal canal and vertebral foramen dimensions. In existing research, technologies such as corrosion and expansion in magnetic resonance image (MRI) processing have also strengthening the accuracy of results. Indicators such as area and Intersection over Union (IoU)are also provided for assessment. Among them, the mean average precision (mAP), for identifying intervertebral foramen (IVF) and intervertebral disc (IVD) through YOLOv4 is 95.6%. Resnet50 mixing U-Net was employed to identify the spinal canal and intervertebral foramen and achieved IoU scores of 79.11% and 80.89%.

Background: Prediction of neurorehabilitation outcomes after a Spinal Cord Injury (SCI) is crucial for healthcare resource management and improving prognosis and rehabilitation strategies. Arti-ficial neural networks (ANNs) have emerged as a promising alternative to conventional statistical approaches for identifying complex prognostic factors in SCI patients. Materials: a database of 1256 SCI patients admitted for rehabilitation was analyzed. Clinical and demographics data and SCI characteristics, were used to predict functional outcomes using both ANN and linear regression models. The former was structured with input, hidden, and output layers, while the linear regression identified significant variables affecting outcomes. Both ap-proaches aimed to evaluate and compare their predictive accuracy for rehabilitation outcomes measured by the Spinal Cord Independence Measure (SCIM) score. Results: Both ANN and linear regression models identified key predictors of functional outcomes, such as age, injury level, and initial SCIM scores (correlation with actual outcome: R=0.75 and 0.73, respectively). When alimented also with parameters recorded during hospitalization, the ANN highlighted the importance of these additional factors like motor completeness and compli-cations during hospitalization, showing an improvement in its predictive accuracy (R=0.87). Conclusion: ANN seemed to be not widely superior to classical statistics in general, but, taking into account complex and non-linear relationships among variables, emphasized the impact of complications during the hospitalization on recovery, particularly respiratory issues, deep vein thrombosis, and urological complications. These results suggested that the management of com-plications is crucial for improving functional recovery in SCI patients.

Keywords: Spine surgery 1; Metastatic spinal cord compression 2; Spinal metastasis 3; Cancer treatment.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

Background: Spinal schwannomas and meningiomas are the most common spinal cord benign tumors in adults and total excision is the goal of the treatment. The traditional surgical approach is performed by total laminectomy, but recently unilateral hemilaminectomy has been recognized as a valuable surgical alternative. We report the clinical results of patients affected by spinal schwannoma and meningioma in whom total laminectomy or unilateral hemilaminectomy were performed. Material and Methods: A retrospective study of patients who underwent resection of spinal meningioma or schwannoma by laminectomy or unilateral hemilaminectomy approaches in our Institute from January 2013 to January 2023 was made. The baseline data of these patients, operative approach and postoperative outcome were compared. Results: The study was performed on 41 patients with mean age of 62.5 ±14.6 years. Our series included 24 (59%) cases of schwannomas and 17 (41%) cases of meningiomas, with a prevalent location in the thoracic spine. The average schwannomas volume was 3,6 ±2,7 cm3, whereas the average meningiomas volume was 1.1 ±0.5 cm3. Total excision was achieved in all cases. Operative time of schwannomas was longer (p=0.001) respect to meningiomas with higher intra-operative blood loss (p=0.000). Total laminectomy approach was performed in 24 out of 41 patients (59%) and unilateral hemilaminectomy approach in 17 out of 41 (41%) patients. Unilateral hemilaminectomy was associated with shorter postoperative bed rest (p=0.003), shorter hospitalization (p=0.028) and lower postoperative pain (p=0.02) respect to total laminectomy. Conclusions: Both spinal schwannomas and spinal meningiomas in various size can be safely and effectively treated with unilateral hemilaminectomy approach. This approach grants more advantages compared with standard total laminectomy, including shorter postoperative bed rest, shorter hospitalization and reduced postoperative pain.

This report elucidates the first surgical correction of an infundibular muscular ventricular septal defect (VSD) in a one-year-old Ragdoll cat via cardiac arrest using cardiopulmonary bypass, a method that is rarely used in feline cardiac surgery. VSDs can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. This case involved a VSD that was atypically located and classified under the Soto classification instead of the standard Kirklin classification. Detailed echocardiography revealed that the defect required intervention owing to left heart and main pulmonary artery enlargement. Despite the VSD being located on the contralateral side, as anticipated in the preoperative examinations, the choice of median sternotomy allowed for successful closure of the defect. Conversely, the insertion of two cannulas into the ascending aorta resulted in damage to the adjacent thoracic duct, causing transient chylothorax, which resolved with conservative treatment. Cardiac arrest induced by a cardioplegic solution facilitated the surgical procedure, although it has led to anemia in cats. However, on postoperative day 490, the patient exhibited only minor residual shunting with normalized heart size, and remained healthy. This technique appears to be a viable treatment option for congenital heart disease in cats.

Kinesio tape is considered one of the most common techniques which using recently, where it is used as a therapeutic technique for pain relief, correction of joint position, prevention of oedema and injuries, improve range of motion and muscular activity for the individual. This study is a descriptive research design and aims to identify the effect of using Kinesio tape on the neuromuscular activity of quadriceps muscle after the rehabilitation program of the knee joint. The study sample consists of (10) players from different sports (football, basketball …etc.) and suffering from knee joint injuries. This sample was taken from Kafr-El sheikh and Kaleen club. Results showed that Kinesio tape doesn’t have any explicit effect on the neuromuscular activity of muscle but acts as a catalyst for muscle and promote a person’s feeling of psychological wellbeing and reassurance.When comparing results of using Kinesio tape during performing leg squatting and balance test with not using tape, founded that when performing leg squatting and balance test with using Kinesio tape, there were significant effects on muscle activity compared to not using it.

Wear simulation aims to assess wear rates and their dependence on factors like load, kinematics, temperature, and implant orientation. Despite its significance, there's a notable gap in research concerning advancements in simulator control systems and the testing of clinically relevant waveforms. This study addresses this gap by focusing on enhancing the conventional proportional-integral-derivative (PID) controller used in joint simulators through the development of a fuzzy logic-based controller. Leveraging a single-input-multiple-output (SIMO) fuzzy logic control system, the study aimed to improve displacement control, augmenting the traditional Proportional-Integral (PI) tuning approach. Implementation and evaluation of a novel Fuzzy-PI control algorithm were conducted on the Leeds spine wear simulator. The study also included testing of daily-living (DL) profiles, particularly from the hip joint, to broaden the scope of simulation scenarios. While both the conventional PI controller and the Fuzzy-PI controller met ISO tolerance criteria for the spine flexion-extension (FE) profile at 1Hz, the Fuzzy-PI controller demonstrated superior performance at higher frequencies and with DL profiles due to its real-time adaptive tuning capability. The Fuzzy-PI controller represents a significant advancement in joint wear simulation, offering improved control functionalities and a more accurate emulation of real-world physiological dynamics.

Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine co-releasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play key roles in the regulation of pain, locomotive movement, and respiratory rhythms. Herein, we first describe GABAergic and glycinergic transmission and inhibitory networks, which consist of three types of terminals, in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many of GABAergic neurons convert to co-releasing state. The co-releasing neurons and terminals remain in the dorsal horn, whereas many of co-releasing ones ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.

The aim of the study was to assess the relationship between the shape of the anterior-posterior curvature of the spine and body composition in school-children. The study included 257 children, aged 11-12. Correct spinal curvature was established in 106 (41.08%) subjects. Other types included: decreased kyphosis and correct lordosis - 40 participants (15.50%), correct kyphosis and decreased lordosis - 24 individuals (9.30%), increased kyphosis and correct lordosis - 17 subjects (6.59%), correct kyphosis and increased lordosis - 22 children (8.53%), decreased kyphosis and decreased lordosis - 32 people (12.40%), decreased kyphosis and increased lordosis - 4 of the examined subjects (1.55%), increased kyphosis and lordosis - 13 people (5.04%). In addition, 134 (51.94%) demonstrated scoliotic posture and 8 (3.10%) scoliosis. There were significant relationships between the shape of the anterior-posterior curvatures and body composition in school-children. Those with a strong body build (predominance of mesomorphs) were generally characterised by the correct formation of these curvatures. In contrast, lean people (with the predominance of ectomorphic factors) were more likely to experience abnormalities. No correlations with body composition were observed in the group with scoliotic posture or scoliosis.

Brown-Séquard Syndrome (BSS) is a rare spinal cord injury characterized by asymmetrical motor and sensory dysfunction. Trauma to the spinal cord, particularly the hemi section, is the primary cause. Diagnosis involves a thorough medical history, physical examination, and imaging studies. Treatment focuses on stabilization, rehabilitation, and potential emerging therapies. This article provides a comprehensive overview of BSS, including its causes, symptoms, diagnosis, and treatment.

Transcutaneous electrical stimulation of the spinal cord is used to restore locomotion and body weight support in patients with severe motor disorders. We studied effects of this non-invasive stimulation on postural control in healthy subjects. Stimulation at the L1-L2 vertebrae was performed to activate the extensor muscles of the lower limbs. Because postural regulation depends on the cognitive style, the effects of the stimulation were analyzed separately in field-dependent (FD) and field-independent (FI) participants. During the study young adults (N=16, half FD and half FI participants, all right dominant leg) stood on a force platform in a soundproof chamber with their eyes closed. Stimulation was applied in the midline between the L1-L2 vertebrae or over the left or right dorsal roots of the spinal cord; under control condition there was no stimulation. Stimulation destabilized posture in healthy subjects, whereas patients with movement disorders usually showed an improvement in postural control. In FD participants, left dorsal root and midline stimulation increased several postural parameters by up to 30%. Dorsal root stimulation on the side of the supporting leg reduced postural control, while stimulation on the side of the dominant leg did not. No significant changes were observed in the FI participants.

Background Main treatment modality for spinal meningiomas (SM) is gross total resection (GTR). However, optimal timing of surgery, especially in cases with absent or mild neurological symptoms remains unclear. The aim of this study is to assess the impact of early-stage resection on neurological outcome, quality of life (QoL) and quality of care. The primary objective was a favorable neurological outcome (McCormick scale 1); Methods: We retrospectively analyzed data from patients operated on SM between 2011 and 2021. Patients with mild neurological symptoms preoperatively (McCormick scale 1 and 2) were compared to those with more severe neurological symptoms (McCormick scale 3-5). Disabilities and QoL were assessed according to validated questionnaires (SF36, ODI, NDI). Results: Age, spinal cord edema, thoracic localization, and spinal canal occupancy ratio were associated with more severe neurological symptoms (all p<.05). Patients presented with mild symptoms were associated with favorable neurological outcome (OR: 14.778 (95%CI 3.918-55.746, p<.001), which is associated with shorter hospitalization, better QoL and less disabilities (p<.05). Quality of care was comparable in both cohorts; Conclusions: Early surgical intervention of SM, before the development of severe neurological deficits, should be considered as it is associated with a favorable neurological outcome and quality of life.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene - resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with development of cardiomyopathy - the leading cause of death - inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD – treatment is aimed at delaying disorder progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial stress has recently come into focus as a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but effects of such agents on cardiac function remain unclear. Synergistic integration of small molecule- and gene-target-based drugs with metabolic, immune, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.

Background: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder that has no curative treatment. Diagnosis is based on a set of criteria established by Gilman (1998 and 2008) and recently updated by Wenning (2022). We aim to determine the effectiveness of [123I]Ioflupane SPECT in MSA, especially at the initial clinical suspicion. Methods: Cross-sectional study of patients at initial clinical suspicion of MSA, referred for [123I]Ioflupane SPECT. Results: 139 patients (68 men, 71 women) were included, 104 being MSA-probable and 35 MSA-possible. MRI was normal in 89.2% while SPECT was positive in 78.45%. SPECT showed high sensitivity (82.46%) and positive predictive value (86.24), reaching maximum sensitivity in MSA-P (97.26%). Significant differences were found when relating both SPECT assessments in the healthy-sick and inconclusive-sick groups. We also found an association when relating SPECT to the subtype (MSA-C or MSA-P), as well as to the presence of parkinsonian symptoms. Lateralization of striatal involvement was detected (left side). Conclusions: [123I]Ioflupane SPECT is a useful and reliable tool for diagnosing MSA, with good effectiveness and accuracy. Qualitative assessment shows a clear superiority when distinguishing between the healthy-sick categories, as well as between the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes at initial clinical suspicion.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

The interplay between Diffuse Idiopathic Skeletal Hyperostosis (DISH) and the gut microbiota represents a compelling area of research, offering insights into the relationship between spinal degenerative diseases and the gut's microbial inhabitants. This comprehensive review seeks to unravel the complex connection, shedding light on its implications for human health and potential therapeutic avenues. A crucial section dives into the world of gut microbiota (GM), exploring its impact on human health, featuring its defining characteristics, and highlighting its role in metabolism, immunomodulation, host interaction, and how its composition changes over time. The subsequent portion delves into the relationship between microbiome composition and pathological bone development, including the link between Intervertebral Disc Degeneration (IDD) and gut inflammation, emphasizing how gut inflammation and GM dysbiosis play pivotal roles. Further dissecting the interconnections, various axes of influence, including the gut-spine axis, gut-bone axis, gut-joint axis, gut-disc axis (specific to DISH), gut-ligament axis, and gut-muscle axis, are discussed. Of particular interest is the section on the impact of GM on DISH-derived pain, addressing a critical aspect of the condition's manifestation. The review discusses the potential of GM modulation as a treatment for DISH, providing hope for therapeutic advancements. Additionally, it highlights the positive impact of lifestyle interventions, such as dietary modifications, sleep optimization, and exercise regimens, in mitigating GM dysbiosis and potentially improving DISH outcomes. Lastly, the intriguing prospect of fecal microbiome transplant and its implications for DISH management is examined, opening new avenues for research and therapeutic interventions. In conclusion, this comprehensive review underscores the intricate interplay between DISH and the gut microbiota, offering a fresh perspective on the impact of GM on spinal degenerative diseases. It emphasizes the potential for innovative treatments, such as GM modulation and lifestyle interventions, and presents fecal microbiome transplant as an exciting area for future exploration.

Background: In spinal cord injury, radical treatment is still a persistent hope for patients and clinicians. Our study aimed to determine the different histological changes in central, cranial and caudal sites of compressed spinal cord as a result of neuroectodermal stem cells (NESCs) transplantation in rats. Material and methods: For extraction of NESCs, future brains were extracted from mice embryos (10-days old) and cultured. Eighty, male rats were divided randomly into control, sham (20 rats each); while 40 rats were subjected to compressed spinal cord injury (CSCI). Seven days after spinal cord injury, rats were subdivided into 2 groups (20 rats each); an untreated and treated with NESCs injected cranial and caudal to the site of the spinal cord injury. Rats were sacrificed 4 weeks after transplantations of NESCs and specimens from the spinal cord at the central, cranial and caudal to site of spinal cord injury were proceeded to be stained with haematoxylin & eosin, osmic acid and Immunohistochemistry of glial fibrillary acidic protein (GFAP). Results: Sections of CSCI revealed areas of hemorrhages, necrosis and cavitation limited by reactive astrocytosis, with upregulation of GFAP expression. Evidence of remyelination and mitigation of histopathological features, reactive astrocytosis in CSCI sections were more pronounced in cranial than in caudal region. Conclusions: NESCs transplantation ameliorated the pathological changes, promoted remyelination.

We recently reported that in the spinal cord of PPMS or SPMS patients, large areas of periplaque demyelinating lesions extend distance away from plaque borders. Such lesions are characterized by a progliotic TGF-beta 1 signature accompanied by: i) a low-grade inflammatory reaction, ii) an extensive astrocytosis and iii) a process of incomplete demyelination. It was proposed that, while efficiently dampening inflammation in MS spinal cords, TGF-beta 1 could promote astrocytosis, prevent remyelination and possibly trigger alterations of myelin synthesis. In light of these findings, a re-interpretation of two large neuropathological studies performed on MS brains and spinal cords is provided here. While results from these studies clearly showed that active plaques do not display any region-specific distribution, an important point was apparently overlooked and not discussed by the authors: a significantly higher percentage of inactive plaques was found in MS spinal cords as compared to brains and, conversely, the percentage of slowly-expanding (or smoldering) lesions was significantly lower in the spinal cord as compared to the brain. These data indicate that the spinal cord environment may be more favorable to the resolution of inflammation. Downstream of the autoimmune process leading to plaque formation, region-specific mechanisms may thus drive the outcome of active plaques. While inflammation triggers tissue destruction, inflammation may also be needed for effective tissue repair and an inappropriate dampening of inflammatory events may possibly translate into a poor level of remyelination in MS spinal cords. It is proposed here that TGF-beta 1 is involved in such a brain-spinal cord dissociation of active plaques outcome.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Study design : Technical note. Objectives: To present a new spinal shortening technique for tethered cord syndrome. Background : Tethered cord syndrome (TCS) is a debilitating condition of progressive neurological decline. Surgical detethering for TCS is a gold standard. However, symptomatic retethering of TCS has been reported in 5%–50% of patients after initial release. To solve this problem, posterior spinal shortening osteotomy has been reported. This technique has risks of massive blood loss and neurological deterioration. The authors hereby report a new safe spinal shortening technique for tethered cord syndrome. Materials and Methods : A 31-year-old man with gait disturbance was referred to our hospital. After the delivery, he underwent surgical untethering of spinal cord in another hospital. He had hyperreflexia of Achilles tendon reflex and muscle weakness of bilateral legs (MMT 3-4). He also had urinary and bowel incontinence, and total sensory loss below L5.Anteroposterior lumbar radiogram indicates partial laminectomy of L3 and L4. Lumbar MRI showed retethering of spinal cord. Results: He underwent new spinal shortening technique for tethered cord syndrome under the guidance of O-arm navigation. First, from anterior approach disectomy from T12 to L3 was performed. Second, from posterior Ponte osteotomy was done from T12 to L3, shorten the spinal column 15 mm. The patient was successfully treated surgically. Postoperative lumbar MRI showed the tension of spinal cord was released. Manual muscle testing results and sensory function of the left leg had recovered almost fully on final follow-up at one year. Conclusions/Level of Evidence: Retethered spinal cord after initial untethering was difficult to treat. This new spinal shortening technique was effective and very safe technique to release the tension of spinal cord. Level V.

The operating theatre represents a key contributor to healthcare-derived emissions. Here, we outline the carbon footprint of a lumbar microdiscectomy at our regional unit in Greater Manchester, with the use of AI technology. In doing so, we aim to define the extent of the environmental impact and identify carbon hotspots for sustainable change. Our unit of analysis covered the start of the patient journey into hospital through to the final outpatient appointment. Publicly available and locally sourced data was used. An inventory analysis of two lumbar microdiscectomies was conducted. Each item was categorised reconciled against our AI-powered ‘CO2 analysis’ database. Kilograms of carbon dioxide equivalent (kg CO2e) was chosen as the primary measure of impact. An average lumbar microdiscectomy at our trust generates 477.73kg CO2e. The operation (173.89kg CO2e, 36.40%) and the inpatient stay (144.67kg CO2e, 30.28%) constituted the biggest contributors. Single-use intraoperative equipment contributed to over three-quarters of the total emissions from the operation. By defining the environmental burden of elective spinal surgery, we have identified carbon hotspots to target for sustainable change. Substituting polluting elements for carbon-friendly alternatives and challenging the single-use culture, modern healthcare systems can help pave the way to a ‘net zero’ healthcare system.