Muscle eosinophilia is a hallmark of chronic disease in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive myopathy caused by the aberrant increased expression of the DUX4 retrogene in skeletal muscle cells. The DUX4 gene encodes a transcription factor that functions in zygotic genome activation and then is silenced in most adult somatic tissues. DUX4 expression in FSHD disrupts normal muscle cell function; however, the downstream pathogenic mechanisms are still unclear. Histologically, FSHD affected muscles show a characteristic dystrophic phenotype that is often accompanied by a pronounced immune cell infiltration, but the role of the immune system in FSHD is not understood. Previously, we used ACTA1;FLExDUX4 FSHD-like mouse models varying in severity as discovery tools to identify increased Interleukin 6 and microRNA-206 levels as serum biomarkers for FSHD disease severity. In this study, we use the ACTA1;FLExDUX4 chronic FSHD-like mouse model to provide insight into the immune response to DUX4 expression in skeletal muscles. We demonstrate that these FSHD-like muscles are enriched with the chemoattractant eotaxin and the cytotoxic eosinophil peroxidase, and exhibit muscle eosinophilia. We further identified muscle fibers with positive staining for eosinophil peroxidase in human FSHD muscle. Our data supports that skeletal muscle eosinophilia is a hallmark of FSHD pathology.

From monocyte-derived macrophages to resident macrophages-how metabolism leads their way in cancer.

Macrophages are innate immune cells that play key roles during both homeostasis and disease. Depending on the microenvironmental cues sensed in different tissues, macrophages are known to acquire specific phenotypes and exhibit unique features that, ultimately, orchestrate tissue homeostasis, defense, and repair. Within the tumor microenvironment, macrophages are referred to as tumor-associated macrophages (TAMs) and constitute a heterogeneous population. Like their tissue resident counterpart, TAMs are plastic and can switch function and phenotype according to the niche-derived stimuli sensed. While changes in TAM phenotype are known to be accompanied by adaptive alterations in their cell metabolism, it is reported that metabolic reprogramming of macrophages can dictate their activation state and function. In line with these observations, recent research efforts have been focused on defining the metabolic traits of TAM subsets in different tumor malignancies and understanding their role in cancer progression and metastasis formation. This knowledge will pave the way to novel therapeutic strategies tailored to cancer subtype-specific metabolic landscapes. This review outlines the metabolic characteristics of distinct TAM subsets and their implications in tumorigenesis across multiple cancer types.

Portuguese adaptation of the Chronic Heart Failure Knowledge Questionnaire (KQCHF).

BACKGROUND: A patient's knowledge of heart failure (HF) is associated with better outcomes. The more information patients have about their illness, the less likely they are to be readmitted to the hospital. Such knowledge includes the cause, symptoms, probable duration, and expected evolution of the clinical picture. In Portugal, a tool for testing patient knowledge is an unmet need. Therefore, this study aimed to adapt and test the Chronic Heart Failure Knowledge Questionnaire (KQCHF) for the Portuguese context. METHODS: This work includes three cross-sectional studies. In Study 1, subjects were divided between before and after receiving information about HF. In Study 2, participants answered the questionnaire before and after reading the brochure. In Study 3, KQCHF was applied to patients with HF. Studies 1 and 2 were carried out in the general population. Study 3 was carried out with HF outpatients. Convenience sampling was applied to participants in the three studies. RESULTS: In Study 1 (n = 45), those who received information had better scores (9.2 ± 1.9) than those who did not (6.0 ± 2.3). In Study 2 (n = 21), the scores were higher after reading the brochure (10.4 ± 1.7 vs. 6.5 ± 2.9). In Study 3 (n = 169), women had better scores than men (9.1 ± 2.1 vs. 8.3 ± 2.2, overall: 8.5 ± 2.2), and knowledge was correlated with education (r = .340, p < .001) and age (r = -.170, p = .030). CONCLUSION: The Portuguese adaptation of KQCHF captured relevant knowledge about HF and has shown promising results for clinical and research purposes. The questionnaire can be useful in assessing HF patients' knowledge of their disease and as a basis for the implementation of general and personalised educational strategies to improve HF knowledge and, therefore, promote health literacy and self-care.

Combination Therapy With CD147-Targeted Nanoparticles Carrying Phenformin Decreases Lung Cancer Growth.

Lung cancer is one of the most fatal cancers worldwide. Resistance to conventional therapies remains a hindrance to patient treatment. Therefore, the development of more effective anti-cancer therapeutic strategies is imperative. Solid tumors exhibit a hyperglycolytic phenotype, leading to enhanced lactate production; and, consequently, its extrusion to the tumor microenvironment. Previous data reveals that inhibition of CD147, the chaperone of lactate transporters (MCTs), decreases lactate export in lung cancer cells and sensitizes them to phenformin, leading to a drastic decrease in cell growth. In this study, the development of anti-CD147 targeted liposomes (LUVs) carrying phenformin is envisioned, and their efficacy is evaluated to eliminate lung cancer cells. Herein, the therapeutic effect of free phenformin and anti-CD147 antibody, as well as the efficacy of anti-CD147 LUVs carrying phenformin on A549, H292, and PC-9 cell growth, metabolism, and invasion, are evaluated. Data reveals that phenformin decreases 2D and 3D-cancer cell growth and that the anti-CD147 antibody reduces cell invasion. Importantly, anti-CD147 LUVs carrying phenformin are internalized by cancer cells and impaired lung cancer cell growth in vitro and in vivo. Overall, these results provide evidence for the effectiveness of anti-CD147 LUVs carrying phenformin in compromising lung cancer cell aggressiveness.

Designing and building OSCEBot ® for virtual OSCE - Performance evaluation.

With AI's advancing technology and chatbots becoming more intertwined in our daily lives, pedagogical challenges are occurring. While chatbots can be used in various disciplines, they play a particularly significant role in medical education. We present the development process of OSCEBot ®, a chatbot to train medical students in the clinical interview approach. The SentenceTransformers, or SBERT, framework was used to develop this chatbot. To enable semantic search for various phrases, SBERT uses siamese and triplet networks to build sentence embeddings for each sentence that can then be compared using a cosine-similarity. Three clinical cases were developed using symptoms that followed the SOCRATES approach. The optimal cutoffs were determined, and each case's performance metrics were calculated. Each question was divided into different categories based on their content. Regarding the performance between cases, case 3 presented higher average confidence values, explained by the continuous improvement of the cases following the feedback acquired after the sessions with the students. When evaluating performance between categories, it was found that the mean confidence values were highest for previous medical history. It is anticipated that the results can be improved upon since this study was conducted early in the chatbot deployment process. More clinical scenarios must be created to broaden the options available to students.

Predictors of Portuguese teachers' use of Information and Communication Technologies in literacy classes.

In the last years, the teaching and learning of literacy has changed due to the development of Information and Communication Technologies (ICT). The use of ICT in the classroom depends largely on teachers, who are the key players in its integration. However, several factors influence teachers' decisions to use ICT in their classroom, both internal (e.g., self-efficacy) and external (e.g., school support). Indeed, despite the potential benefits of using ICT, not all teachers use them in their teaching practice. In the present study, we examined which are the main factors influencing teachers' effective use of ICT in literacy classrooms. A total of 125 teachers lecturing Portuguese Language in grades 5-12 participated in this study (M = 50.00 years, SD = 7.88; 89% women). Teachers filled in an online survey, comprising sociodemographic questions (viz., age, gender, education, years of teaching experience, teaching level, school type, and geographical area) and four questionnaires related to ICT and teaching. Results showed that effective use of ICT was predicted by both internal (ICT' self-efficacy and constructivist conception of teaching) and external (lack of access and support, and gatekeepers) factors. These findings may help in the identification of key targets to facilitate the effective use of ICT in literacy classrooms.

Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice.

Background Integrin α7ß1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7ß1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7ß1 is also highly expressed in the heart, but its precise role in cardiac function is unknown. Mutations in the integrin α7 gene (ITGA7) have been reported in children with congenital myopathy. Methods and Results In this study, we described skeletal and cardiac muscle pathology in Itga7-/- mice and 5 patients from 2 unrelated families with ITGA7 mutations. Proband in family 1 presented a homozygous c.806_818del [p.S269fs] variant, and proband in family 2 was identified with 2 intron variants in the ITGA7 gene. The complete absence of the integrin α7 protein in muscle supports the ITGA7 mutations are pathogenic. We performed electrocardiography, echocardiography, or cardiac magnetic resonance imaging, and histological biopsy analyses in patients with ITGA7 deficiency and Itga7-/- mice. The patients exhibited cardiac dysrhythmia and dysfunction from the third decade of life and late-onset respiratory insufficiency, but with relatively mild limb muscle involvement. Mice demonstrated corresponding abnormalities in cardiac conduction and contraction as well as diaphragm muscle fibrosis. Conclusions Our data suggest that loss of integrin α7 causes a novel form of adult-onset cardiac dysfunction indicating a critical role for the integrin α7ß1 in normal cardiac function and highlights the need for long-term cardiac monitoring in patients with ITGA7-related congenital myopathy.

Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies in adults, displaying a progressive, frequently asymmetric involvement of a typical muscles' pattern. FSHD is associated with epigenetic derepression of the polymorphic D4Z4 repeat on chromosome 4q, leading to DUX4 retrogene toxic expression in skeletal muscles. Identifying biomarkers that correlate with disease severity would facilitate clinical management and assess potential FSHD therapeutics' efficacy. OBJECTIVES: This study purpose was to analyze serum cytokines to identify potential biomarkers in a large cohort of adult patients with FSHD. METHODS: We retrospectively measured the levels of 20 pro-inflammatory and regulatory cytokines in sera from 100 genetically confirmed adult FSHD1 patients. Associations between cytokine concentrations and various clinical scores were investigated. We then measured serum and muscle interleukin 6 (IL-6) levels in a validated FSHD-like mouse model, ranging in severity and DUX4 expression. RESULTS: IL-6 was identified as the only cytokine with a concentration correlating with several clinical severity and functional scores, including Clinical Severity Score, Manual Muscle Testing sum score, Brooke and Vignos scores. Further, FSHD patients displayed overall IL-6 levels more than twice high as control, and patients with milder phenotypes exhibited lower IL-6 serum concentration than those with severe muscular weakness. Lastly, an FSHD-like mouse model analysis confirmed that IL-6 levels positively correlate with disease severity and DUX4 expression. CONCLUSIONS: Serum IL-6, therefore, shows promise as a serum biomarker of FSHD severity in a large cohort of FSHD1 adult patients.

Identification of candidate miRNA biomarkers for facioscapulohumeral muscular dystrophy using DUX4-based mouse models.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by misexpression of DUX4 in skeletal myocytes. As DUX4 is the key therapeutic target in FSHD, surrogate biomarkers of DUX4 expression in skeletal muscle are critically needed for clinical trials. Although no natural animal models of FSHD exist, transgenic mice with inducible DUX4 expression in skeletal muscles rapidly develop myopathic phenotypes consistent with FSHD. Here, we established a new, more-accurate FSHD-like mouse model based on chronic DUX4 expression in a small fraction of skeletal myonuclei that develops pathology mimicking key aspects of FSHD across its lifespan. Utilizing this new aged mouse model and DUX4-inducible mouse models, we characterized the DUX4-related microRNA signatures in skeletal muscles, which represent potential biomarkers for FSHD. We found increased expression of miR-31-5p and miR-206 in muscles expressing different levels of DUX4 and displaying varying degrees of pathology. Importantly, miR-206 expression is significantly increased in serum samples from FSHD patients compared with healthy controls. Our data support miR-31-5p and miR-206 as new potential regulators of muscle pathology and miR-206 as a potential circulating biomarker for FSHD. This article has an associated First Person interview with the first author of the paper.

Useful Ultrasonographic Parameters to Predict Difficult Laryngoscopy and Difficult Tracheal Intubation-A Systematic Review and Meta-Analysis.

Unexpected difficult airway management can cause significant morbidity and mortality in patients admitted for elective procedures. Ultrasonography is a promising tool for perioperative airway assessment, nevertheless it is still unclear which sonographic parameters are useful predictors of difficult laryngoscopy and tracheal intubation. To determine the ultrasonographic predictors of a difficult airway that could be applied for routine practice, a systematic review and meta-analysis was conducted. Literature search was performed on PubMED, Web of Science and Embase using the selected keywords. Human primary studies, published in English with the use of ultrasonography to prediction of difficult laryngoscopy or tracheal intubation were included. A total of 19 articles (4,570 patients) were analyzed for the systematic review and 12 articles (1,141 patients) for the meta-analysis. Standardized mean differences between easy and difficult laryngoscopy groups were calculated and the parameter effect size quantified. A PRISMA methodology was used and the critical appraisal tool from Joanna Briggs Institute was applied. Twenty-six sonographic parameters were studied. The overall effect of the distance from skin to hyoid bone (p = 0.02); skin to epiglottis (p = 0.02); skin to the anterior commissure of vocal cords (p = 0.02), pre-epiglottis space to distance between epiglottis and midpoint between vocal cords (p = 0.01), hyomental distance in neutral (p < 0.0001), and extended (p = 0.0002) positions and ratio of hyomental distance in neutral to extended (p = 0.001) was significant. This study shows that hyomental distance in the neutral position is the most reliable parameter for pre-operative airway ultrasound assessment. The main limitations of the study are the small sample size, heterogeneity of studies, and absence of a standardized ultrasonographic evaluation method [Registered at International prospective register of systematic reviews (PROSPERO): number 167931].

Investigations of Olive Oil Industry By-Products Extracts with Potential Skin Benefits in Topical Formulations.

The by-products of olive oil industry are a major ecological issue due to their phenolic content, highly toxic organic load, and low pH. However, they can be recovered and reused, since their components have antioxidant, anti-inflammatory, and photoprotector properties. In this work, oil-in-water creams containing three different olive oil industry by-products extracts were produced without the use of organic solvents. First, the extracts were thoroughly characterized in vitro for cytotoxicity, inhibition of skin enzymes, and antioxidant and photoprotection capacities. Safety studies were then performed, including ocular and skin irritation tests, ecotoxicity evaluation, and in vivo Human Repeat Insult Patch Test. The results obtained in this initial characterization supported the incorporation of the extracts in the cream formulations. After preparation, the creams were characterized for their organoleptic, physicochemical, droplet size and rheological properties, and microbial contamination. The results showed that all formulations were semi-solid creams, with stable pH, compatible with the skin, without microbial contamination, and with the expected droplet size range. The rheological analysis showed shear-thinning behavior with yield stress, with the viscosity decreasing with increasing shear rate. The oscillatory results suggest that the creams have a strong network structure, being easily rubbed into the skin. Finally, compatibility, acceptability and antioxidant efficacy were evaluated in vivo, in human volunteers. No adverse reactions were observed after application of the formulations on skin and the cream with the highest concentrations of phenolic compounds showed the highest antioxidant efficiency. In conclusion, the results suggest that olive oil industry by-products extracts have valuable properties that favor their re-use in the cosmetic industry. The example presented here showed their successful incorporation into creams and their impact in these formulations' appearance, pH, and rheological performance, as well as their in vivo compatibility with skin and antioxidant efficiency.

Targeting lactate production and efflux in prostate cancer.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men worldwide. Screening and management of PCa remain controversial and, therefore, the discovery of novel molecular biomarkers is urgently needed. Alteration in cancer cell metabolism is a recognized hallmark of cancer, whereby cancer cells exhibit high glycolytic rates with subsequent lactate production, regardless of oxygen availability. To maintain the hyperglycolytic phenotype, cancer cells efficiently export lactate through the monocarboxylate transporters MCT1 and MCT4. The impact of inhibiting lactate production/extrusion on PCa cell survival and aggressiveness was investigated in vitro and ex vivo using primary tumor and metastatic PCa cell lines and the chicken embryo chorioallantoic membrane (CAM) model. In this study, we showed the metastatic PCa cell line (DU125) displayed higher expression levels of MCT1/4 isoforms and glycolysis-related markers than the localized prostate tumor-derived cell line (22RV1), indicating these proteins are differentially expressed throughout prostate malignant transformation. Moreover, disruption of lactate export by MCT1/4 silencing resulted in a decrease in PCa cell growth and motility. To support these results, we pharmacological inhibited lactate production (via inhibition of LDH) and release (via inhibition of MCTs) and a reduction in cancer cell growth in vitro and in vivo was observed. In summary, our data provide evidence that MCT1 and MCT4 are important players in prostate neoplastic progression and that inhibition of lactate production/export can be explored as a strategy for PCa treatment.

Injury to the Superior Gluteal Artery during Intramedullary Fixation of a Proximal Femoral Fracture - A Case Report.

INTRODUCTION: Proximal femoral fractures represent a health problem of global proportions. Iatrogenic vascular lesion in the treatment of these fractures is an unusual potentially lethal complication, reported in only 0.2% of trochanteric fractures treated with intramedullary implants. Superior gluteal artery injury is extremely rare, with only two cases reported in literature. CASE REPORT: A 66-year-old Caucasian woman, with metastatic disease, was admitted with a right pertrochanteric fracture. She underwent closed reduction and long intramedullary nail fixation. Five days post-operatively, a sudden hemoglobin drop occurred. A computed tomography demonstrated an extensive hematoma. Angiography confirmed an arterial bleeding from the superior gluteal artery and subsequent selective embolization was successfully performed. CONCLUSION: The presence of anemia and thigh hematoma that progressively worsens post-operatively should raise the diagnostic suspicion of an iatrogenic vascular injury. To the best of our knowledge, this is only the third case reported of superior gluteal artery injury after intramedullary fixation of a proximal femoral fracture. We describe the post-operative course and management strategy and hope this will contribute to the global knowledge and increase awareness of these rare injuries.

Novel and Modified Neutrophil Elastase Inhibitor Loaded in Topical Formulations for Psoriasis Management.

Human neutrophil elastase (HNE) is a serine protease that degrades matrix proteins. An excess of HNE may trigger several pathological conditions, such as psoriasis. In this work, we aimed to synthesize, characterize and formulate new HNE inhibitors with a 4-oxo-ß-lactam scaffold with less toxicity, as well as therapeutic index in a psoriasis context. HNE inhibitors with 4-oxo-ß-lactam scaffolds were synthesized and characterized by NMR, FTIR, melting point, mass spectrometry and elemental analysis. In vitro cytotoxicity and serine protease assays were performed. The compound with the highest cell viability (AAN-16) was selected to be incorporated in an emulsion (AAN-16 E) and in a microemulsion (AAN-16 ME). Formulations were characterized in terms of organoleptic properties, pH, rheology, droplet size distribution, in vitro drug release and in vivo psoriatic activity. All compounds were successfully synthesized according to analytical methodology, with good yields. Both formulations presented suitable physicochemical properties. AAN-16 E presented the most promising therapeutic effects in a murine model of psoriasis. Overall, new HNE inhibitors were synthesized with high and selective activity and incorporated into topical emulsions with potential to treat psoriasis.

Lactate and Lactate Transporters as Key Players in the Maintenance of the Warburg Effect.

Reprogramming of energy metabolism is a key hallmark of cancer. Most cancer cells display a glycolytic phenotype, with increased glucose consumption and glycolysis rates, and production of lactate as the end product, independently of oxygen concentrations. This phenomenon, known as "Warburg Effect", provides several survival advantages to cancer cells and modulates the metabolism and function of neighbour cells in the tumour microenvironment. However, due to the presence of metabolic heterogeneity within a tumour, cancer cells can also display an oxidative phenotype, and corruptible cells from the microenvironment become glycolytic, cooperating with oxidative cancer cells to boost tumour growth. This phenomenon is known as "Reverse Warburg Effect". In either way, lactate is a key mediator in the metabolic crosstalk between cancer cells and the microenvironment, and lactate transporters are expressed differentially by existing cell populations, to support this crosstalk.In this review, we will focus on lactate and on lactate transporters in distinct cells of the tumour microenvironment, aiming at a better understanding of their role in the acquisition and maintenance of the direct/reverse "Warburg effect" phenotype, which modulate cancer progression.

Laminin-111 protein therapy enhances muscle regeneration and repair in the GRMD dog model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce muscle pathology and improve muscle function in the mdx mouse model for DMD. In this study, we examined the ability of msLam-111 to prevent muscle disease progression in the golden retriever muscular dystrophy (GRMD) dog model of DMD. The msLam-111 protein was injected into the cranial tibial muscle compartment of GRMD dogs and muscle strength and pathology were assessed. The results showed that msLam-111 treatment increased muscle fiber regeneration and repair with improved muscle strength and reduced muscle fibrosis in the GRMD model. Together, these findings support the idea that Laminin-111 could serve as a novel protein therapy for the treatment of DMD.

Preoperative halo-gravity traction with and without anterior release for severe scoliosis / Tracção halogravitacional com e sem libertação anterior no tratamento de escoliose grave / Tracción preoperatoria de halo-gravedad con y sin liberación anterior en escoliosis grave

ABSTRACT Objective: This study aims to compare the use of halo-gravity traction (HGT) with and without previous anterior release, in terms of curve reduction, for the treatment of pediatric severe spinal deformity. Methods: From 2010 to 2016, all patients treated with HGT prior to instrumentation for scoliosis and kyphoscoliosis were reviewed. They were assessed by deformity etiology, previous anterior release, instrumentation procedure used, traction protocol, major Cobb angle before traction, after the protocol, and after the instrumentation procedure. Twelve patients met these criteria and constituted the sample groups: Group I (n=7) with anterior release and Group II (n=5) without anterior release. Results: The average pre-traction major curve Cobb angles were 114.9o and 108.4º for Group I and II, respectively (P>0.05). After HGT, both groups achieved a significant reduction in curve angle (P<0.05). Group I presented an average Cobb angle of 95.0o after HGT, representing a 17.3% (19.8o) curve reduction. Group II presented a Cobb angle of 80.1o, representing a 25.2% (28.4o) curve reduction. The difference between the two groups in relation to the reduction of major curve after HGT was not statistically significant (P=0.073). After the surgical procedure, the correction achieved was significantly improved (P<0.05), without statistically significant difference between the two groups (P>0.05). No major HGT related complications were reported. Conclusions: Anterior release prior to HGT did not increase major curve correction after posterior surgery for severe pediatric idiopathic and syndromic scoliosis. HGT is an effective and safe technique, though it frequently presents minor and transitory complications. Level of Evidence III; Retrospective Comparative Study.

RESUMO Objetivo: O presente estudo tem como objectivo comparar a utilização de tracção halo-gravitacional (THG), com e sem libertações anteriores prévias, no que diz respeito à correcção da curva no tratamento de escoliose grave pediátrica. Métodos: Foram avaliados retrospectivamente doentes com escoliose/cifoescoliose, tratados com THG prévia ao procedimento instrumentado, entre 2010 e 2016. Foi avaliada a etiologia da deformidade, realização de libertações discais prévias, tipo de procedimento instrumentado, protocolo da THG, ângulo de Cobb da curva major previamente à THG, após protocolo e após procedimento instrumentado. Doze doentes satisfaziam os critérios de inclusão: Grupo I (n=7) com libertações anteriores prévias e Grupo II (n=5) sem libertações prévias. Resultados: O ângulo Cobb médio da curva major era 114,9o e 108,4º para o Grupo I e II respectivamente (P>0,05). Após THG, ambos os grupos apresentaram redução significativa da curva major (P<0,05). O Grupo I apresentava um ângulo Cobb médio de 95,0o, representando redução de 17,3% (19,8o). O Grupo II apresentava um ângulo Cobb médio de 80,1o, representando redução de 25,2% (28,4o). Após THG não existiu diferença significativa entre os grupos, no que diz respeito à redução da curva major (P=0,073). Após instrumentação, a correcção aumentou de forma significativa (P<0,05), sem diferença estatisticamente significativa entre os dois grupos (P=0.05). Não existiram complicações major relacionadas com a THG. Conclusões: Libertações discais prévias à THG não parecem aumentar a correcção final da curva major, no tratamento de escoliose pediátrica grave. A THG é um método efectivo e seguro. Nível de Evidência III; Estudo Retrospectivo Comparativo.

RESUMEN Objetivo: Este estudio tiene como objetivo comparar el uso de la tracción de halo-gravedad (THG) con y sin liberación anterior previa, con respecto a la reducción de la curva en el tratamiento de la deformidad espinal pediátrica grave. Métodos: Entre 2010 y 2016, se revisaron todos los pacientes tratados con THG antes de la instrumentación para escoliosis y cifoescoliosis. Se evaluaron por etiología de la deformidad, liberación anterior previa, tipo de instrumentación, protocolo de tracción, ángulo de Cobb mayor antes de la tracción, después del protocolo y después de la instrumentación. Doce pacientes cumplieron los criterios de inclusión y constituyeron los grupos de muestra: Grupo I (n = 7) con liberación anterior y Grupo II (n = 5) sin liberación anterior. Resultados: El promedio de los ángulos de Cobb de la curva principal antes de la tracción fue de 114,9o y 108,4° para el grupo I y II, respectivamente (P > 0,05). Después de la THG, ambos grupos lograron una reducción significativa en el ángulo de la curva (P > 0,05). El Grupo I tenía ángulo Cobb promedio de 95o, después de la THG, lo que representa una reducción de la curva del 17,3% (19,8o). El Grupo II tenía ángulo de Cobb de 80,1º, que representa una reducción de la curva del 25,2% (28,4o). La diferencia entre los dos grupos en relación con la reducción de la curva principal después de la THG no fue estadísticamente significativa (P = 0.073). Después del procedimiento quirúrgico, la corrección mejoró de manera expresiva (P > 0,05), aunque sin diferencia estadísticamente significativa entre los dos grupos (P > 0,05). No se informaron complicaciones mayores relacionadas con la THG. Conclusiones: La liberación anterior previa a la THG no aumentó la corrección de la curva principal después de la cirugía posterior para la escoliosis pediátrica idiopática y sindrómica grave. La THG es una técnica efectiva y segura, aunque con frecuencia presenta complicaciones menores y transitorias. Nivel de Evidencia III; Estudio Retrospectivo Comparativo.

Sunitinib promotes myogenic regeneration and mitigates disease progression in the mdx mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal, muscle degenerative disease causing premature death of affected children. DMD is characterized by mutations in the dystrophin gene that result in a loss of the dystrophin protein. Loss of dystrophin causes an associated reduction in proteins of the dystrophin glycoprotein complex, leading to contraction-induced sarcolemmal weakening, muscle tearing, fibrotic infiltration and rounds of degeneration and failed regeneration affecting satellite cell populations. The α7ß1 integrin has been implicated in increasing myogenic capacity of satellite cells, therefore restoring muscle viability, increasing muscle force and preserving muscle function in dystrophic mouse models. In this study, we show that a Food and Drug Administration (FDA)-approved small molecule, Sunitinib, is a potent α7 integrin enhancer capable of promoting myogenic regeneration by stimulating satellite cell activation and increasing myofiber fusion. Sunitinib exerts its regenerative effects via transient inhibition of SHP-2 and subsequent activation of the STAT3 pathway. Treatment of mdx mice with Sunitinib demonstrated decreased membrane leakiness and damage owing to myofiber regeneration and enhanced support at the extracellular matrix. The decreased myofiber damage translated into a significant increase in muscle force production. This study identifies an already FDA-approved compound, Sunitinib, as a possible DMD therapeutic with the potential to treat other muscular dystrophies in which there is defective muscle repair.

Acceptance of Mobile Health Applications: Examining Key Determinants and Moderators.

Mobile health applications are increasingly numerous and varied. However, despite high expectations and large budgets involved in their development they are often rejected by potential users, and little is known on why this happens. This study aimed to fill this gap by investigating the determinants of technology acceptance and its moderators. Aligned with the Unified Theory of Acceptance and Use of Technology, we examined the moderating roles of age, gender, and smartphone experience in the relationship between technology acceptance determinants (performance expectancy, effort expectancy, social influence, and facilitating conditions) and the intention to use mobile health applications (N = 394, 18-65 years). A stepwise multiple linear regression was conducted. Results showed that the intention to use mobile health applications was determined by performance expectancy moderated by age and smartphone experience, and that the role of the other determinants depended on age and gender (e.g., more intention to use in older men if less effort, and in younger men if better facilitating conditions). These findings show that user characteristics are relevant moderators and should be considered when targeting specific populations to use mobile health applications.

Clinimetric Properties of the Brief Fatigue Inventory Applied to Oncological Patients Hospitalized for Chemotherapy.

BACKGROUND: The clinimetric properties of the Brief Fatigue Inventory (BFI) were not previously assessed in oncological patients hospitalized for chemotherapy. OBJECTIVE: To assess the reliability and validity of the construct, ceiling and floor effects, and responsiveness of the BFI administered to oncological patients hospitalized for chemotherapy. METHODS: This test-retest study included 100 oncological patients hospitalized for chemotherapy. The clinimetric properties tested were as follows: internal consistency (Cronbach's alpha), reliability (intraclass correlation coefficient [ICC2,1] and 95% CI), agreement (standard error of measurement and minimum difference changed [MDC90%]), validity of the construct (Pearson's correlation [r] with the Piper Fatigue Scale), responsiveness (effect size [ES] and correlation), and ceiling and floor effects (minimum and maximum score frequencies). The BFI was applied on the first day of chemotherapy and 48 hours and 15 days after the start of chemotherapy. RESULTS: The BFI presented adequate values of internal consistency (α Cronbach = 0.94), substantial reliability [ICC2,1 (95% CI) = 0.87 (0.81 to 0.91)] and very good agreement (standard error of measurement = 1% and MDC90% = -0.37). The BFI had a positive and strong correlation with the Piper Fatigue Scale (r = 0.84; P < 0.001). Internal responsiveness was considered moderate (ES = 0.5), and external responsiveness was absent. A floor effect was present (35%). CONCLUSION: BFI applied to oncological patients hospitalized for chemotherapy replicates its original version with adequate reliability, validity, and internal responsiveness. However, in this population, the BFI showed a floor effect.