Actors, Institutions, and Policies.

This paper aims to characterize the main actors in the Brazilian pharmaceutical industry - national companies, foreign companies and public laboratories - and analyze how they were affected and how they reacted to changes over the last 30 years in the institutional framework. The results show that national companies have been gaining prominence in the Brazilian pharmaceutical market with their internationalization movement and their strengthening of innovation strategies.

A gain-of-function HCN4 mutant in the HCN domain is responsible for inappropriate sinus tachycardia in a Spanish family.

In a family with inappropriate sinus tachycardia (IST), we identified a mutation (p.V240M) of the hyperpolarization-activated cyclic nucleotide-gated type 4 (HCN4) channel, which contributes to the pacemaker current (I) in human sinoatrial node cells. Here, we clinically study fifteen family members and functionally analyze the p.

Severe congenital X-linked myopathy with excessive autophagy secondary to an apparently synonymous but pathogenic novel variant.

X-linked myopathy with excessive autophagy is a rare inherited disease characterized by aberrant accumulation of autophagic vacuoles in skeletal muscle. Affected males usually show a slow progression and the heart is characteristically spared. We present four male patients from the same family with an extremely aggressive form of this disease, requiring permanent mechanical ventilation from birth.

Modeling a Dynamic Printability Window on Polysaccharide Blend Inks for Extrusion Bioprinting.

Extrusion-based bioprinting is one of the most widespread technologies due to its affordability, wide range of processable materials, and ease of use. However, the formulation of new inks for this technique is based on time-consuming trial-and-error processes to establish the optimal ink composition and printing parameters. Here, a dynamic printability window was modeled for the assessment of the printability of polysaccharide blend inks of alginate and hyaluronic acid with the intent to build a versatile predictive tool to speed up the testing procedures.

The Potential of Endoscopic Spring Ligament Repair in Flatfoot Reconstruction.

Background: Spring ligament fulfills 2 main important functions: one, supporting the head of the talus and stabilizing the talonavicular joint, and the other, maintaining the longitudinal arch by acting as a static support. In this preliminary report, we describe an endoscopic repair for spring ligament injuries with modified portals.

Methods: We performed a retrospective case series study from February 2019 to January 2022.

Ly6C monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology.

Gammaherpesviruses (γHVs) have coevolved with their host, leading to a remarkably high infection prevalence and establishment of latency. The lifelong persistence of γHVs in hosts appears to broadly shape host immunity, and we show here that pulmonary infection with Murid herpesvirus 4 (MuHV-4), a mouse γHV, drives the recruitment of Ly6C monocytes (MOs) into the airway, thereby modulating the host immune response. The absence of Ly6C MOs is associated with severe virus-induced immunopathology and the systemic release of inflammatory mediators.

Accuracy of multidetector computed tomography with maximum intensity projection technique in the assessment of fissure integrity.

Background: Bronchoscopic lung volume reduction (BLVR) is a potential treatment for patients with severe emphysema, performed through the placement of unidirectional endobronchial valves (EBVs). Their benefits are only achieved in patients that significantly reduce lobar volume, and it is mandatory that the fissures are complete. Fissure evaluation is preferably done by computed tomography, but little is known if its evaluation corresponds to the anatomical findings.

Brain Arousal as Measured by EEG-Assessment Differs Between Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Depression.

Disturbed regulation of vigilance in the wake state seems to play a key role in the development of mental disorders. It is assumed that hyperactivity in adult ADHD is an attempt to increase a general low vigilance level via external stimulation in order to avoid drowsiness. For depression, the avoidance of stimulation is interpreted as a reaction to a tonic increased vigilance state.

Regression of Left Ventricular Hypertrophy in a Case of Sarcomeric Hypertrophic Cardiomyopathy: An Unexpected Outcome.

We present a case of sarcomeric hypertrophy cardiomyopathy diagnosed in a child who had hypertrophy degree regression during adolescence, with no left ventricular dysfunction and no increase of the ventricular diameters. ().

Minimally invasive neurectomy for Morton's neuroma with interdigital approach. Long term results.

Background: "Morton's Neuroma" is a frequent cause of chronic forefoot pain. It can affect general population, including athletes, and can lead to progressive foot pain and discomfort for daily life activities and sports.

Hypothesis/purpose: Our objective is to evaluate the long-term results in a series of 85 feet, operatively treated with minimally invasive interdigital approach for neurectomy.

The effects of the oral supplementation of L-Cystine associated with reduced L-Glutathione-GSH on human skin pigmentation: a randomized, double-blinded, benchmark- and placebo-controlled clinical trial.

Background: Glutathione has become a potential skin-lightening ingredient after the discovery of its anti-melanogenic properties. Various mechanisms of action have been considered to explain this property, one of them being the skewing of the melanin synthesis pathway toward the production of lighter pheomelanin instead of darker eumelanin, consequently producing a lightening effect.

Aims: To evaluate the skin lightening and anti-dark spot effects of oral supplementation with L-Cystine associated with L-Glutathione as compared to placebo and benchmark.

Amphiphilic copolymers in biomedical applications: Synthesis routes and property control.

The request of new materials, matching strict requirements to be applied in precision and patient-specific medicine, is pushing for the synthesis of more and more complex block copolymers. Amphiphilic block copolymers are emerging in the biomedical field due to their great potential in terms of stimuli responsiveness, drug loading capabilities and reversible thermal gelation. Amphiphilicity guarantees self-assembly and thermoreversibility, while grafting polymers offers the possibility of combining blocks with various properties in one single material.

Results of catheter ablation with zero or near zero fluoroscopy in pediatric patients with supraventricular tachyarrhythmias.

Introduction And Objectives: Ionizing radiation exposure in catheter ablation procedures carries health risks, especially in pediatric patients. Our aim was to compare the safety and efficacy of catheter ablation guided by a nonfluoroscopic intracardiac navigation system (NFINS) with those of an exclusively fluoroscopy-guided approach in pediatric patients.

Methods: We analyzed catheter ablation results in pediatric patients with high-risk accessory pathways or supraventricular tachycardia referred to our center during a 6-year period.

Utilization of Quantitative Computed Tomography Assessment to Identify Bronchiolitis Obliterans Syndrome After Single Lung Transplantation.

Objective: To evaluate quantitative chest computed tomography (CT) methods for the detection of air trapping (AT) and to assess its diagnostic performance for the diagnosis of bronchiolitis obliterans syndrome (BOS) in single lung transplant (SLT) patients.

Methods: Adult patients who had a SLT at a single transplant center and underwent CT scan after transplantation were retrospectively included. CT findings of air trapping were measured by three different methods: expiratory air-trapping index (ATIexp), mean lung density on expiratory acquisition (MLDexp) and expiratory to inspiratory ratio of mean lung density (E/I-ratio(MLD).

Effect of Preoperative Infusion of Levosimendan on Biomarkers of Myocardial Injury and Haemodynamics After Paediatric Cardiac Surgery: A Randomised Controlled Trial.

Objective: The aim was to test the hypothesis that preoperative infusion of levosimendan would decrease patients' cardiac biomarker profiles during the immediate postoperative stage (troponin I and B-type natriuretic peptide levels) more efficiently than placebo after cardiopulmonary bypass.

Methods: In a randomised, placebo-controlled, double-blinded study, 30 paediatric patients were scheduled for congenital heart disease surgery. 15 patients (50%) received prophylactic levosimendan and 15 patients (50%) received placebo from 12 h before cardiopulmonary bypass to 24 h after surgery.

Impact of angiotensin II type 1 and G-protein-coupled Mas receptor expression on the pulmonary performance of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial disease with a mean survival of about 2.5-5 years after diagnosis. Its pathophysiology is still a major challenge for science.

Flatfoot Deformity Due to Isolated Spring Ligament Injury.

Patients with acquired flatfoot deformity due to isolated injury of the spring ligament, with healthy posterior tibialis tendon, are rarely identified. Between December 2004 and September 2011 (6 years and 9 months), we treated 10 patients with acquired flatfoot deformity due to spring ligament injury without tibialis posterior tendon tear. One patient (10%) was lost to follow-up.

Intermuscular S-ICD Implantation in Pediatric Patients.

The use of conventional implantable cardioverter-defibrillators (ICDs) in children presents important technical challenges. We present the surgical technique necessary to adapt the subcutaneous ICD (S-ICD) implantation designed for adults, to children, including patients weighing less than 20 kg. The implant procedure implies a two-incision technique and interfascial serratus anterior-latissimus dorsi dissection to accommodate the device.

Locally instructed CXCR4 neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps.

Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps.

Preclinical evaluation of topically-administered PEGylated Fab' lung toxicity.

PEGylation is a promising approach to increase the residence time of antibody fragments in the lungs and sustain their therapeutic effects. However, concerns arise as to the potential pulmonary toxicity of antibody fragments conjugated to high molecular weight (HMW) polyethylene glycol (PEG), notably after repeated administrations, and the possibility of PEG accumulation in the lungs. The purpose of this proof-of-concept study is to give insights about the safety of lung administration of a Fab' anti-IL17A antibody fragment conjugated to two-armed 40 kDa PEG (PEG40).

Genetic Mosaicism in Calmodulinopathy.

Background: CaM (calmodulin) mutations are associated with congenital arrhythmia susceptibility (calmodulinopathy) and are most often de novo. In this report, we sought to broaden the genotype-phenotype spectrum of calmodulinopathies with 2 novel calmodulin mutations and to investigate mosaicism in 2 affected families.

Methods: CaM mutations were identified in 4 independent cases by DNA sequencing.