Reporting of confidence intervals, achievement of intended sample size, and adjustment for multiple primary outcomes in randomised trials of physical therapy interventions: an analysis of 100 representatively sampled trials.

BACKGROUND: The physical therapy profession has made efforts to increase the use of confidence intervals due to the valuable information they provide for clinical decision-making. Confidence intervals indicate the precision of the results and describe the strength and direction of a treatment effect measure. OBJECTIVES: To determine the prevalence of reporting of confidence intervals, achievement of intended sample size, and adjustment for multiple primary outcomes in randomised trials of physical therapy interventions. METHODS: We randomly selected 100 trials published in 2021 and indexed on the Physiotherapy Evidence Database. Two independent reviewers extracted the number of participants, any sample size calculation, and any adjustments for multiple primary outcomes. We extracted whether at least one between-group comparison was reported with a 95 % confidence interval and whether any confidence intervals were interpreted. RESULTS: The prevalence of use of confidence intervals was 47 % (95 % CI 38, 57). Only 6 % of trials (95 % CI: 3, 12) both reported and interpreted a confidence interval. Among the 100 trials, 59 (95 % CI: 49, 68) calculated and achieved the required sample size. Among the 100 trials, 19 % (95 % CI: 13, 28) had a problem with unadjusted multiplicity on the primary outcomes. CONCLUSIONS: Around half of trials of physical therapy interventions published in 2021 reported confidence intervals around between-group differences. This represents an increase of 5 % from five years earlier. Very few trials interpreted the confidence intervals. Most trials reported a sample size calculation, and among these most achieved that sample size. There is still a need to increase the use of adjustment for multiple comparisons.

Integrating waste valorization and symbiotic microorganisms for sustainable bioremediation of metal(loid)-polluted soils.

Remediation strategies for metal(loid)-polluted soils vary among the wide range of approaches, including physical, chemical, and biological remediation, or combinations of these. In this study, we assessed the effectiveness of a set of soil remediation treatments based on the combined application of inorganic (marble sludge) and organic amendments (vermicompost, and dry olive residue [DOR] biotransformed by the saprobic fungi Coriolopsis rigida and Coprinellus radians) and inoculation with arbuscular mycorrhizal fungi (AMFs) (Rhizophagus irregularis and Rhizoglomus custos). The treatments were applied under greenhouse conditions to soil residually polluted by potentially toxic elements (PTEs) (Pb, As, Zn, Cu, Cd, and Sb), and wheat was grown in the amended soils to test the effectiveness of the treatments in reducing soil toxicity and improving soil conditions and plant performance. Therefore, we evaluated the influence of the treatments on the main soil properties and microbial activities, as well as on PTE availability and bioaccumulation in wheat plants. Overall, the results showed a positive influence of all treatments on the main soil properties. Treatments consisting of a combination of marble and organic amendments, especially biotransformed DOR amendments, showed the greatest effectiveness in improving the soil biological status, promoting plant growth and survival, and reducing PTE availability and plant uptake. Furthermore, AMF inoculation further enhanced the efficacy of DOR amendments by promoting the immobilization of PTEs in soil and stimulating the phytostabilization mechanisms induced by AMFs, thus playing an important bioprotective role in plants. Therefore, our results highlight that biotransformed DOR may represent an efficient product for use as a soil organic amendment when remediating metal(loid)-polluted soils, and that its application in combination with AMFs may represent a promising sustainable bioremediation strategy for recovering soil functions and reducing toxicity in polluted areas.

Personal support networks of young people with and without intellectual disability. A comparative study.

BACKGROUND: Previous studies show that the personal support networks of people with intellectual disability are smaller and less diverse than those of people without intellectual disability. This article aims to compare the characteristics of the personal networks of young people with and without intellectual disability. METHOD: The Personal Network Analysis (McCarty, Revista Hispana Para El Análisis de Redes Sociales, 2010, 19, 242-271) was applied. The participants comprised 51 young people aged between 13 and 19, of whom 27 had an intellectual disability. The Egonet programme was used to compile information, and SPSS v.27 for the statistical analysis. RESULTS: Young people with intellectual disabilities have smaller personal networks than people without disability, while they also comprise more people with disability and fewer 'friends' and support people. CONCLUSIONS: The full social inclusion of people with intellectual disability requires schools, families, the community and the individual to work together to develop activities that help them initiate and maintain relationships, prioritising mainstream contexts.

Two thousand years of garden urbanism in the Upper Amazon.

A dense system of pre-Hispanic urban centers has been found in the Upano Valley of Amazonian Ecuador, in the eastern foothills of the Andes. Fieldwork and light detection and ranging (LIDAR) analysis have revealed an anthropized landscape with clusters of monumental platforms, plazas, and streets following a specific pattern intertwined with extensive agricultural drainages and terraces as well as wide straight roads running over great distances. Archaeological excavations date the occupation from around 500 BCE to between 300 and 600 CE. The most notable landscape feature is the complex road system extending over tens of kilometers, connecting the different urban centers, thus creating a regional-scale network. Such extensive early development in the Upper Amazon is comparable to similar Maya urban systems recently highlighted in Mexico and Guatemala.

Preoperative respiratory muscle training reduces the risk of pulmonary complications and the length of hospital stay after cardiac surgery: a systematic review.

QUESTIONS: What is the effect of preoperative respiratory muscle training (RMT) on the incidence of postoperative pulmonary complications (PPCs) after open cardiac surgery? What is the effect of RMT on the duration of mechanical ventilation, postoperative length of stay and respiratory muscle strength? DESIGN: Systematic review of randomised trials with meta-analysis. PARTICIPANTS: Adults undergoing elective open cardiac surgery. INTERVENTION: The experimental groups received preoperative RMT and the comparison groups received no intervention. OUTCOME MEASURES: The primary outcomes were PPCs, length of hospital stay, respiratory muscle strength, oxygenation and duration of mechanical ventilation. The methodological quality of studies was assessed using the PEDro scale and the overall certainty of the evidence was assessed using the GRADE approach. RESULTS: Eight trials involving 696 participants were included. Compared with the control group, the respiratory training group had fewer PPCs (RR 0.51, 95% CI 0.38 to 0.70), less pneumonia (RR 0.44, 95% CI 0.25 to 0.78), shorter hospital stay (MD -1.7 days, 95% CI -2.4 to -1.1) and higher maximal inspiratory pressure values at the end of the training protocol (MD 12 cmH2O, 95% CI 8 to 16). The mechanical ventilation time was similar in both groups. The quality of evidence was high for pneumonia, length of hospital stay and maximal inspiratory pressure. CONCLUSION: Preoperative RMT reduced the risk of PPCs and pneumonia after cardiac surgery. The training also improved the maximal inspiratory pressure and reduced hospital stay. The effects on PPCs were large enough to warrant use of RMT in this population. REGISTRATION: CRD42021227779.

Predicting disease severity in multiple sclerosis using multimodal data and machine learning.

BACKGROUND: Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity. METHODS: We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Assessment of the algorithm performance was conducted in an independent prospective cohort of 271 MS patients from a single centre. RESULTS: We found algorithms for predicting confirmed disability accumulation for the different scales, no evidence of disease activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in both cohorts. CONCLUSION: Combining clinical, imaging and omics data with machine learning helps identify MS patients at risk of disability worsening.

Technosols Derived from Mining, Urban, and Agro-Industrial Waste for the Remediation of Metal(loid)-Polluted Soils: A Microcosm Assay.

This study evaluated the effectiveness of six Technosols designed for the remediation of polluted soils (PS) by metal(loid)s at physicochemical, biological, and ecotoxicological levels and at a microcosm scale. Technosols T1-T6 were prepared by combining PS with a mix of organic and inorganic wastes from mining, urban, and agro-industrial activities. After two months of surface application of Technosols on polluted soils, we analysed the soil properties, metal(loid) concentration in total, soluble and bioavailable fractions, soil enzymatic activities, and the growth responses of Trifolium campestre and Lactuca sativa in both the Technosols and the underlying polluted soils. All Technosols improved the unfavourable conditions of polluted soils by neutralising acidity, increasing the OC, reducing the mobility of most metal(loid)s, and stimulating both the soil enzymatic activities and growths of T. campestre and L. sativa. The origin of organic waste used in the Technosols strongly conditioned the changes induced in the polluted soils; in this sense, the Technosols composed of pruning and gardening vermicompost (T3 and T6) showed greater reductions in toxicity and plant growth than the other Technosols composed with different organic wastes. Thus, these Technosols constitute a potential solution for the remediation of persistent polluted soils that should be applied in large-scale and long-term interventions to reinforce their feasibility as a cost-effective ecotechnology.

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.

Gender Bias When Using Artificial Intelligence to Assess Anorexia Nervosa on Social Media: Data-Driven Study.

BACKGROUND: Social media sites are becoming an increasingly important source of information about mental health disorders. Among them, eating disorders are complex psychological problems that involve unhealthy eating habits. In particular, there is evidence showing that signs and symptoms of anorexia nervosa can be traced in social media platforms. Knowing that input data biases tend to be amplified by artificial intelligence algorithms and, in particular, machine learning, these methods should be revised to mitigate biased discrimination in such important domains. OBJECTIVE: The main goal of this study was to detect and analyze the performance disparities across genders in algorithms trained for the detection of anorexia nervosa on social media posts. We used a collection of automated predictors trained on a data set in Spanish containing cases of 177 users that showed signs of anorexia (471,262 tweets) and 326 control cases (910,967 tweets). METHODS: We first inspected the predictive performance differences between the algorithms for male and female users. Once biases were detected, we applied a feature-level bias characterization to evaluate the source of such biases and performed a comparative analysis of such features and those that are relevant for clinicians. Finally, we showcased different bias mitigation strategies to develop fairer automated classifiers, particularly for risk assessment in sensitive domains. RESULTS: Our results revealed concerning predictive performance differences, with substantially higher false negative rates (FNRs) for female samples (FNR=0.082) compared with male samples (FNR=0.005). The findings show that biological processes and suicide risk factors were relevant for classifying positive male cases, whereas age, emotions, and personal concerns were more relevant for female cases. We also proposed techniques for bias mitigation, and we could see that, even though disparities can be mitigated, they cannot be eliminated. CONCLUSIONS: We concluded that more attention should be paid to the assessment of biases in automated methods dedicated to the detection of mental health issues. This is particularly relevant before the deployment of systems that are thought to assist clinicians, especially considering that the outputs of such systems can have an impact on the diagnosis of people at risk.

Myofascial stiffness of plantar fascia and Achilles tendon in individuals with plantar fasciopathy: An observational cross-sectional study.

BACKGROUND: Assessment of myofascial tissue stiffness have a role in identifying physical impairments in plantar fasciopathy (PF). It is still unclear which specific functional and tissue differences exist between individuals with PF. AIM: To compare myofascial stiffness of plantar fascia, Achilles tendon, and triceps surae between symptomatic and asymptomatic limbs in individuals with PF and between individuals with and without PF. METHODS: Thirty nine individuals diagnosed with PF and individuals with no history of PF were recruited. Myofascial stiffness of the plantar fascia, Achilles tendon, and triceps surae, range of motion, and clinical tests were performed. Mean difference (MD) and 95% confidence interval (CI) were calculated. RESULTS: Individuals with PF showed lower mean stiffness in Achilles tendon insertion (MD = -1.00 N/mm; 95%CI: -1.80,-0.21) on the symptomatic limb compared to the corresponding symptomatic limb in control group, a lower mean stiffness in plantar fascia (MD = -0.16 N/mm; 95%CI: -0.30, -0.01) on the symptomatic limb compared to asymptomatic limb, and a lower mean stiffness in the region 3 cm above the Achilles tendon insertion (MD = -0.79; 95%CI: -1.59, -0.00) compared to control. Individuals with PF showed fewer repetitions in heel rise test (MD = -3.97 reps; 95%CI: -5.83, -2.12) and in the step-down test (MD = -5.23 reps; 95%CI: -7.02, -3.44) compared to control. CONCLUSIONS: Individuals with PF present reduced stiffness in Achilles tendon insertion and plantar fascia. The reduced stiffness was more evident in Achilles tendon in individuals with PF compared to individuals without PF. Individuals with PF showed lower performance in clinical tests.

Editorial for the Special Issue "Phytotoxicity of Heavy Metals in Contaminated Soils".

Soil is an essential natural resource because of the ecosystem services it carries out in the terrestrial ecosystem: the provision of food, fibre and fuel; habitats for organisms; nutrient cycling; climate regulation and carbon sequestration; water purification and soil contaminant reductions; and others [...].

Digital educational technology content production and validity about Japanese bathtub (ofurô) in neonatal unit.

OBJECTIVE: To describe the elaboration and content validity stages of a digital educational technology for nursing professionals about Japanese bathtub (ofurô) in newborns in neonatal care units. METHOD: A methodological study conducted between August 2019 and July 2021, in a public maternity hospital in Manaus, Amazonas, developed in two stages. In the first, the e-book images, text and editing were produced. In the second, material content validity was carried out, through the opinion of 15 expert judges, nurses and neonatal care experts. In data analysis, the percentage of agreement was applied with agreement score estimation. Items with 80% or more agreement were considered valid. RESULTS: The e-book "Japanese bathtub: manual for nursing professionals" was produced, organized into nine sessions, which describe the technique execution. Content was considered valid by expert judges (general score 90%). CONCLUSION: The e-book was considered suitable for use in training nursing professionals, with potential for dissemination of knowledge regarding humanization of care for premature babies.

Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response.

Aging associated defects within stem cell-supportive niches contribute towards age-related decline in stem cell activity. However, mechanisms underlying age-related niche defects, and whether restoring niche function can improve stem cell fitness, remain unclear. Here, we sought to determine whether aged blood stem cell function can be restored by rejuvenating their supportive niches within the bone marrow (BM). We identify Netrin-1 as a critical regulator of BM niche cell aging. Niche-specific deletion of Netrin-1 induces premature aging phenotypes within the BM microenvironment, while supplementation of aged mice with Netrin-1 rejuvenates aged niche cells and restores competitive fitness of aged blood stem cells to youthful levels. We show that Netrin-1 plays an essential role in maintaining active DNA damage responses (DDR), and that aging-associated decline in niche-derived Netrin-1 results in DNA damage accumulation within the BM microenvironment. We show that Netrin-1 supplementation is sufficient to resolve DNA damage and restore regenerative potential of the aged BM niche and blood stem cells to endure serial chemotherapy regimens.

Ecotoxicological Assessment of Polluted Soils One Year after the Application of Different Soil Remediation Techniques.

The present work evaluated the influence of eight different soil remediation techniques, based on the use of residual materials (gypsum, marble, vermicompost) on the reduction in metal(loid)s toxicity (Cu, Zn, As, Pb and Cd) in a polluted natural area. Selected remediation treatments were applied in a field exposed to real conditions and they were evaluated one year after the application. More specifically, five ecotoxicological tests were carried out using different organisms on either the solid or the aqueous (leachate) fraction of the amended soils. Likewise, the main soil properties and the total, water-soluble and bioavailable metal fractions were determined to evaluate their influence on soil toxicity. According to the toxicity bioassays performed, the response of organisms to the treatments differed depending on whether the solid or the aqueous fraction was used. Our results highlighted that the use of a single bioassay may not be sufficient as an indicator of toxicity pathways to select soil remediation methods, so that the joint determination of metal availability and ecotoxicological response will be determinant for the correct establishment of any remediation technique carried out under natural conditions. Our results indicated that, of the different treatments used, the best technique for the remediation of metal(loid)s toxicity was the addition of marble sludge with vermicompost.

Autonomic Function Recovery and Physical Activity Levels in Post-COVID-19 Young Adults after Immunization: An Observational Follow-Up Case-Control Study.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but the literature on long-term recovery of young adults after mild to moderate infection is lacking. Heart rate variability (HRV) allows for the observation of autonomic nervous system (ANS) modulation post-SARS-CoV-2 infection. Since physical activity (PA) can help improve ANS modulation, investigating factors that can influence HRV outcomes after COVID-19 is essential to advancements in care and intervention strategies. Clinicians may use this research to aid in the development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general anamnesis was performed, followed by HRV and PA assessment. Thus, 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (two doses) and assessments were repeated. Over the follow-up period, a decrease in sympathetic (SNS) activity (mean heart rate: p = 0.0024, CI = -24.67--3.26; SNS index: p = 0.0068, CI = -2.50--0.32) and increase in parasympathetic (PNS) activity (mean RR: p = 0.0097, CI = 33.72-225.51; PNS index: p = 0.0091, CI = -0.20-1.47) were observed. At follow-up, HRV was not different between groups (p > 0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

Polymorphisms and gene expression of metalloproteinases and their inhibitors associated with cerebral ischemic stroke in young patients with sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is a genetic disease with great clinical heterogeneity and few viable strategies for treatment; hydroxyurea (HU) is the only widely used drug. Thus, the study of single nucleotide polymorphisms (SNPs) and the gene expression of MMPs 1, 2, 9, 7 and TIMPs 1 and 2, which are involved in the regulation of extracellular matrix, inflammation, and neuropathies, may provide further insights into the pathophysiology of the disease and elucidate biomarkers and molecules as potential therapeutic targets for patients with SCA. METHODS AND RESULTS: We evaluated 251 young individuals with SCA from northeastern Brazil. The groups were divided according to vaso-occlusive crisis (VOC) and cerebrovascular disease (CVD), compared to control individuals. SNP detection and gene expression assays were performed by real-time PCR, TaqMan system®. Both the expression levels of MMP1 gene, and the SNP MMP1-1607 1G/2G were associated with the risk of cerebral ischemic stroke (IS), and the expression of MMP1 was also associated with a higher frequency of VOC/year. Expression levels of MMP7, TIMP1, and TIMP2 were increased in patients conditioned to IS. The SNP 372T>C (rs4898) TIMP1 T alleles were more frequent in patients with > 5 VOC events/year. The SNP rs17576 of MMP9 showed differences in gene expression levels; it was increased in the genotypes AG, and AG+GG. CONCLUSION: The findings of this study, the SNPs, and expression provide initial support for understanding the role of MMPs-TIMPs in the pathophysiology of SCA in young patients.