178 research outputs found
Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy
Skeletal muscle ion channelopathies (SMICs) are a large heterogeneous group of rare genetic disorders caused by mutations in genes encoding ion channel subunits in the skeletal muscle mainly characterized by myotonia or periodic paralysis, potentially resulting in long-term disabilities. However, with the development of new molecular technologies, new genes and new phenotypes, including progressive myopathies, have been recently discovered, markedly increasing the complexity in the field. In this regard, new advances in SMICs show a less conventional role of ion channels in muscle cell division, proliferation, differentiation, and survival. Hence, SMICs represent an expanding and exciting field. Here, we review current knowledge of SMICs, with a description of their clinical phenotypes, cellular and molecular pathomechanisms, and available treatments
Using the Transformative Storytelling Technique to Generate Empowering Narratives for Informal Caregivers:Semistructured Interviews, Thematic Analysis, and Method Demonstration
Background: The transformative storytelling technique is an innovative top-down approach to narrative therapy that aims to provide building blocks for creating flourishing narratives for target groups or populations. This approach acts as a facilitator for implementing the human-centered design in developing digital self-help tools for larger samples or target groups.Objective: This study applied the transformative storytelling technique, as a new approach in mental health, to develop empowering audio narratives for informal caregivers.Methods: A narrative inquiry was conducted with 17 informal caregivers (16 women and 1 man) who completed a semistructured interview, “Caregiver Life Story,” acquiring information about the beginning of the role, rising action, and critical point of the role. The participants' ages ranged from 41 to 84 years, with all participants providing care for at least a 6-month period. This inquiry was guided by the transformative storytelling technique, and aimed to collect data relevant to creating fictional stories based on real-life themes.Results: Twenty-five overall themes were distinguished across three a priori-set categories, providing narrative building blocks for the informal caregiver life stories. The final empowering caregiver life story was created as an example for this study, demonstrating the application of the transformative storytelling technique in an informal care context.Conclusions: The creation of empowering stories for populations or target groups in mental health care requires a unified and guided approach that will follow clear guidelines and storytelling principles. The transformative storytelling technique is a first of its kind in the mental health context, representing an initial step in enabling and supporting the creation of meaningful stories and the development of relatable, but productive, narratives. Such narratives have the potential to serve across media and digital platforms for supporting and improving well-being, and potentially triggering self-change in the target group or population.</p
Effect of Poor Access to Water and Sanitation As Risk Factors for Soil-Transmitted Helminth Infection: Selectiveness by the Infective Route
Background: Soil-transmitted helminth (STH) infections are a public health problem in resource-limited settings worldwide. Chronic STH infection impairs optimum learning and productivity, contributing to the perpetuation of the poverty-disease cycle. Regular massive drug administration (MDA) is the cardinal recommendation for its control; along with water, sanitation and hygiene (WASH) interventions. The impact of joint WASH interventions on STH infections has been reported; studies on the independent effect of WASH components are needed to contribute with the improvement of current recommendations for the control of STH. The aim of this study is to assess the association of lacking access to water and sanitation with STH infections, taking into account the differences in route of infection among species and the availability of adequate water and sanitation at home. Methods and Findings: Cross-sectional study, conducted in Salta province, Argentina. During a deworming program that enrolled 6957 individuals; 771 were randomly selected for stool/serum sampling for parasitological and serological diagnosis of STH. Bivariate stratified analysis was performed to explore significant correlations between risk factors and STH infections grouped by mechanism of entry as skin-penetrators (hookworms and Strongyloides stercoralis) vs. orally-ingested (Ascaris lumbricoides and Trichuris trichiura). After controlling for potential confounders, unimproved sanitation was significantly associated with increased odds of infection of skin-penetrators (adjusted odds ratio [aOR] = 3.9; 95% CI: 2.6–5.9). Unimproved drinking water was significantly associated with increased odds of infection of orally-ingested (aOR = 2.2; 95% CI: 1.3–3.7). Conclusions: Lack of safe water and proper sanitation pose a risk of STH infections that is distinct according to the route of entry to the human host used by each of the STH species. Interventions aimed to improve water and sanitation access should be highlighted in the recommendations for the control of STH.Fil: Echazú, Adriana. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonanno, Daniela. Ministerio de Salud de la Nación. Dirección Nacional de Prevención de Enfermedades y Riesgos; ArgentinaFil: Juarez, Marisa. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Fundación Mundo Sano; ArgentinaFil: Cajal, Silvana P.. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Heredia, Viviana. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Caropresi, Silvia. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Cimino, Rubén Oscar. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caro, Nicolas. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Vargas Flores, Paola Andrea. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paredes, Gladys. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Up-regulation of neural and cell cycle-related microRNAs in brain of amyotrophic lateral sclerosis mice at late disease stage
Altered glucose catabolism in the presynaptic and perisynaptic compartments of SOD1G93A mouse spinal cord and motor cortex indicates that mitochondria are the site of bioenergetic imbalance in ALS
Amyotrophic lateral sclerosis is an adult-onset neurodegenerative disease that develops due to motor neuron death. Several mechanisms occur supporting neurodegeneration, including mitochondrial dysfunction. Recently, we demonstrated that the synaptosomes from the spinal cord of SOD1G93A mice, an in vitro model of presynapses, displayed impaired mitochondrial metabolism at early pre-symptomatic stages of the disease, while perisynaptic astrocyte particles, or gliosomes, were characterized by mild energy impairment only at symptomatic stages. This work aimed to understand whether mitochondrial impairment is a consequence of upstream metabolic damage. We analysed the critical pathways involved in glucose catabolism at presynaptic and perisynaptic compartments. Spinal cord and motor cortex synaptosomes from SOD1G93A mice displayed high activity of hexokinase and phosphofructokinase, key glycolysis enzymes, and of citrate synthase and malate dehydrogenase, key Krebs cycle enzymes, but did not display high lactate dehydrogenase activity, the key enzyme in lactate fermentation. This enhancement was evident in the spinal cord from the early stages of the disease and in the motor cortex at only symptomatic stages. Conversely, an increase in glycolysis and lactate fermentation activity, but not Krebs cycle activity, was observed in gliosomes from the spinal cord and motor cortex of SOD1G93A mice although only at the symptomatic stages of the disease. The cited enzymatic activities were enhanced in spinal cord and motor cortex homogenates, paralleling the time-course of the effect observed in synaptosomes and gliosomes. The observed metabolic modifications might be considered an attempt to restore altered energetic balance and indicate that mitochondria represent the ultimate site of bioenergetic impairment. This article is protected by copyright. All rights reserved
Chronic pain and spinal cord stimulation.
Chronic pain can have a devastating impact and lead to patient isolation. Many people with chronic pain are predisposed to anxiety-depressant symptoms, due to a lower quality life. The aim of the study is to demonstrate how neuromodulation methods, can encourage the reduction of chronic pain and an improvement in the quality of life, therefore advancing the restoration of psychological well-being.We involved 50 patients with a diagnosis of pain that not respond to traditional pharmacological therapies. Interventions: All subject had depression and anxiety symptoms and a low-quality life. We used the spinal cord stimulation treatment and a psychological evaluation for assessment of depression-anxiety symptomatology and the level of quality life.We observed a significant difference in physical functioning, role limitations due to physical health, general health perceptions, vitality, social functioning, role limitations due to emotional problems and mental health.Our study affirms that the perception of chronic pain has a great impact on the perception of psychological well-being, quality of life, and the performance of normal daily social and professional activities
Functional evaluation of awareness in vegetative and minimally conscious state
Objective: The aim of this study was to assess differences in brain activation in a large sample of Vegetative State (VS) and Minimally Conscious State (MCS) patients, using functional magnetic resonance imaging (fMRI). Methods: We studied 50 patients four to seven months after brain injury. By using international clinical criteria and validated behavioural scales such as the Glasgow Coma Scale and the Clinical Unawareness Assessment Scale, the patients were grouped into VS (n=23) and MCS (n=27). All patients underwent to fMRI examination. After 6 months, the patients were reassessed using Glasgow Outcome Scale and Revised Coma Recovery Scale. Results: fMRI showed significant (p<0.01, cluster-corrected) brain activation in the primary auditory cortex bilaterally during the acoustic stimuli in patients with both VS and MCS. However, ten patients clinically classified as VS, showed a pattern of brain activation very similar to that of MCS patients. Six months later, these ten VS patients had significant clinical improvement, evolving into MCS, whereas the other VS patients and patients with MCS remained clinically stable. Conclusion: Brain activity could help in discerning whether the status of wakefulness in VS is also accompanied by partial awareness, as occurs in MCS. This may have very important prognostic implications
Physical activity practiced at a young age is associated with a less severe subsequent clinical presentation in facioscapulohumeral muscular dystrophy
Background: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA). Methods: People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age. Results: 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73-0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51-0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B). Conclusions: PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution
Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA
Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer's dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis
The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients
We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/ 27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality
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