Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing.

The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime.

Genetically engineered eucalyptus expressing pesticidal proteins from for insect resistance: a risk assessment evaluation perspective.

Eucalyptus covers approximately 7.5 million hectares in Brazil and serves as the primary woody species cultivated for commercial purposes. However, native insects and invasive pests pose a significant threat to eucalyptus trees, resulting in substantial economic losses and reduced forest productivity.

Improving Assessment and Learning Environments for Graduate Medical Trainees to Advance Healthcare Language Equity.

Language-appropriate care is critical for equitable, high-quality health care, but educational standards to assure graduate medical trainees are prepared to give such care are lacking. Detailed guidance for graduate medical education is provided by the Accreditation Council for Graduate Medical Education through the following: (1) an assessment framework for competencies, subcompetencies, and milestones for trainees and (2) the Clinical Learning Environment Review (CLER) Pathways for assessment of trainees' learning environments. These tools do not include a robust framework to evaluate trainees' abilities to offer language-appropriate care.

Characterization of heart disease in mucopolysaccharidosis type II mice.

Mucopolysaccharidosis type II (MPSII) is a progressive lysosomal storage disease caused by mutations in the IDS gene, that leads to iduronate 2-sulfatase (IDS) enzyme deficiency. The enzyme catalyzes the first step of degradation of two glycosaminoglycans (GAGs), heparan sulfate (HS) and dermatan sulfate (DS). The consequences of MPSII are progressively harmful and can lead to death by cardiac failure.

Genome Editing Tools for Lysosomal Storage Disorders.

Genome editing has multiple applications in the biomedical field. They can be used to modify genomes at specific locations, being able to either delete, reduce, or even enhance gene transcription and protein expression. Here, we summarize applications of genome editing used in the field of lysosomal disorders.

Association between Sleep Disorders and Sleep Quality in Patients with Temporomandibular Joint Osteoarthritis: A Systematic Review.

Background: Osteoarthritis (OA) is a leading cause of disability, the most common form of chronic disease in the temporomandibular joint (TMJ), and the most severe disease type of temporomandibular disorders (TMD). The etiology of TMD is multifactorial, considering parafunctional habits, sleep bruxism, or sleep disturbance as common factors. Insomnia and apnea are the two most frequent forms of sleep disorders in TMD patients.

Analysis of the Active Measurement Systems of the Thoracic Range of Movements of the Spine: A Systematic Review and a Meta-Analysis.

(1) Objective: to analyze current active noninvasive measurement systems of the thoracic range of movements of the spine. (2) Methods: A systematic review and meta-analysis were performed that included observational or clinical trial studies published in English or Spanish, whose subjects were healthy human males or females ≥18 years of age with reported measurements of thoracic range of motion measured with an active system in either flexion, extension, lateral bending, or axial rotation. All studies that passed the screening had a low risk of bias and good methodological results, according to the PEDro and MINORS scales.

Influence of the COPD Assessment Test respiratory item score on the decision to hospitalize patients with disease exacerbation in a hospital emergency department.

Objectives: The COPD Assessment Test (CAT) measures quality of life in patients with chronic obstructive pulmonary disease (COPD) as well as disease impact on activities of daily living. The questionnaire consists of 8 items related to breathing (cough, phlegm, chest tightness, and breathlessness) and other symptoms (low energy level, sleep disturbances, limitations on daily activities, and confidence when leaving the home). We investigated the relative impact of respiratory versus nonrespiratory scoring on the total CAT score at different moments in the course of COPD exacerbations: baseline (24 hours before an exacerbation), during the exacerbation, 15 days later, and 2 months later.

Protective effects of L-carnitine on behavioral alterations and neuroinflammation in striatum of glutaryl-COA dehydrogenase deficient mice.

Glutaric acidemia type 1 (GA1) is caused by glutaryl-CoA dehydrogenase deficiency that leads to a blockage in the metabolic route of the amino acids lysine and tryptophan and subsequent accumulation of glutaric acid (GA), 3-hydroxyglutaric acids and glutarylcarnitine (C5DC). Patients predominantly manifest neurological symptoms, associated with acute striatal degeneration, as well as progressive cortical and striatum injury whose pathogenesis is not yet fully established. Current treatment includes protein/lysine restriction and l-carnitine supplementation of (L-car).

Genome editing in lysosomal disorders.

Lysosomal disorders are a group of heterogenous diseases caused by mutations in genes that encode for lysosomal proteins. With exception of some cases, these disorders still lack both knowledge of disease pathogenesis and specific therapies. In this sense, genome editing arises as a technique that allows both the creation of specific cell lines, animal models and gene therapy protocols for these disorders.

Preliminary results of PBA-loaded nanoparticles development and the effect on oxidative stress and neuroinflammation in rats submitted to a chemically induced chronic model of MSUD.

Maple syrup urine disease (MSUD) is a genetic disorder that leads the accumulation of branched-chain amino acids (BCAA) leucine (Leu), isoleucine, valine and metabolites. The symptomatology includes psychomotor delay and mental retardation. MSUD therapy comprises a lifelong protein strict diet with low BCAA levels and is well established that high concentrations of Leu and/or its ketoacid are associated with neurological symptoms.

Open-Design for a Smart Cover of a Night-Time Telescope for Day-Time Use.

Robotic observatories are ideal infrastructures that can be remotely accessed by scientists, amateurs, and general public for research and education in Astronomy. Its robotization is a complex process for ensuring autonomy, safety, and coordination among all subsystems. Some observatories, such as Francisco Sanchez's, are equipped with two types of telescopes: one for the night and one for the day.

Network Analysis Reveals Proteins Associated with Aortic Dilatation in Mucopolysaccharidoses.

Mucopolysaccharidoses are caused by a deficiency of enzymes involved in the degradation of glycosaminoglycans. Heart diseases are a significant cause of morbidity and mortality in MPS patients, even in conditions in which enzyme replacement therapy is available. In this sense, cardiovascular manifestations, such as heart hypertrophy, cardiac function reduction, increased left ventricular chamber, and aortic dilatation, are among the most frequent.

The progression of pulmonary arterial hypertension induced by monocrotaline is characterized by lung nitrosative and oxidative stress, and impaired pulmonary artery reactivity.

The time-course of pulmonary arterial hypertension in the monocrotaline (MCT) model was investigated. Male rats were divided into two groups: MCT (received a 60 mg/kg i.p.

Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, that codifies the alpha-L-iduronidase enzyme, which deficiency leads to storage of glycosaminoglycans, with multiple clinical manifestations. One of the leading causes of death in MPS I patients are cardiac complications such as cardiac valve thickening, conduction abnormalities, myocardial dysfunction, and cardiac hypertrophy. The mechanism leading to cardiac dysfunction in MPS I is not entirely understood.

Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells.

Background: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1).

Methods: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine.

Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma.

Background And Aims: We aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC).

Methods: A retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR).

Early Graft Dysfunction Evaluation by Indocyanine Green Plasma Clearance Rate in the Immediate Postoperative Period After Liver Transplantation.

Background: Liver transplantation (LT) has evolved to improve graft and patient survival. Early graft dysfunction (EGD) and primary nonfunction are an important cause of morbi-mortality. We had formulated the scientific hypothesis that the liver function can be evaluated by the indocyanine green (IG) after LT.

Identification of a molecular marker associated with lignotuber in Eucalyptus ssp.

About 95% of Eucalyptus species present an organ known as a lignotuber, a basal woody swelling that holds a large number of dormant buds in a protected position along with carbohydrates and other nutrients. The importance of this trait in Eucalyptus species relates to its regenerative capacity, particularly in the context of coppicing practices and survival in regions of high abiotic stress, especially fire. In this study, we identified and characterized a genomic region associated with the lignotuber trait in commercially important Eucalyptus species by developing a polymorphic marker that co-segregates with lignotuber presence.

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex.

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of α-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB).

Estimated birth prevalence of mucopolysaccharidoses in Brazil.

Several studies have been published on the frequency of the mucopolysaccharidoses (MPS) in different countries. The objective of the present study was to estimate the birth prevalence (BP) of MPS in Brazil. MPS diagnosis registered at MPS-Brazil Network and in Instituto Vidas Raras were reviewed.

Progressive eye pathology in mucopolysaccharidosis type I mice and effects of enzyme replacement therapy.

Background: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by α-L-iduronidase deficiency, resulting in accumulation of glycosaminoglycans (GAG). Ophthalmological manifestations are common in MPS I patients and often lead to visual impairment. Accumulation of GAG in corneal or retinal tissues reduces vision causing corneal opacity and neurosensory complications.

Neonatal nonviral gene editing with the CRISPR/Cas9 system improves some cardiovascular, respiratory, and bone disease features of the mucopolysaccharidosis I phenotype in mice.

Mucopolysaccharidosis type I (MPS I) is caused by deficiency of alpha-L-iduronidase (IDUA), leading to multisystemic accumulation of glycosaminoglycans (GAG). Untreated MPS I patients may die in the first decades of life, mostly due to cardiovascular and respiratory complications. We previously reported that the treatment of newborn MPS I mice with intravenous administration of lipossomal CRISPR/Cas9 complexes carrying the murine Idua gene aiming at the ROSA26 locus resulted in long-lasting IDUA activity and GAG reduction in various tissues.

Renal function and choroidal thickness using swept-source optical coherence tomography in diabetic patients.

Aim: To assess the relationship between choroidal thickness and renal function in diabetic patients.

Methods: Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-naïve diabetic patients. Demographic data included: age, sex, type and course of diabetes.

Wheat storage proteins: changes on the glutenins after wheat infection with different isolates of Fusarium graminearum.

Wheat gluten proteins are decisive for the industrial properties of flour, so alterations resulting from grain infection with Fusarium graminearum produce changes in the glutenin content that affect the baking properties. This work analyzes the high-molecular-weight glutenin changes from wheat flour with different degrees of F. graminearum infection at field, since these proteins are determinant for the quality properties of flour.