LEADERSHIP DEVELOPMENT TRAINING FOR BRAZILIAN ORTHOPEDIC SURGEONS.

Objective: To report on the experience and impressions of the Brazilian orthopedic trauma surgeons attending the Leadership Development Program (LDP) hosted by the Sociedade Brasileira do Trauma Ortopédico (SBTO) in Sao Paulo, Brazil on November 4, 2022. Methods: Forty-eight orthopedic trauma surgeons from five different regions throughout Brazil were provided a link to complete The Big Five Test, a validated online personality assessment. The questionnaire was available in Portuguese and was intended to provide a background on individual personality traits and their influence on interpersonal interactions. The LDP integrated content from literature reviews specific to Latin America, established leadership programs from leading business schools, and various subject matter experts. Prior to the start of the LDP, participants received a pre-course survey evaluating demographic information, a needs assessment, and the prioritization of leadership topics utilizing a 5-point Likert-scale. Attendees participated in the one-day, interactive LDP focusing on the fundamental principles of leadership development, communication, personal development, emotional intelligence and negotiation. Following the LDP, a post-course evaluation was administered to determine the participants' overall experience, and suggestions for LDP improvement. Results: Forty-one of the forty-eight course participants completed the pre-course evaluation, whereas forty-six of the forty-eight participants completed the post-course evaluations. Overwhelmingly, the lack of opportunity was most prevalently reported as the main obstacle to attending a leadership course, as cited by 56% of respondents. Conclusion: Expanding the accessibility, diversity, and customizability of leadership programs can facilitate the development of personal tools needed to move healthcare forward. Critical topics include emotional intelligence and other differentiating leadership qualities that distinguish true transformational and servant leaders. Advancing leadership skills can stimulate networking, expose learners to experiential learning styles, inspire others to create positive change, and engender creative solutions for systematic improvements and health outcomes. Level of Evidence III; Individual Case-Control Studies.

Objetivo: Relatar a experiência e as impressões de cirurgiões de trauma ortopédico brasileiros participantes do Programa de Desenvolvimento de Liderança (PDL), organizado pela Sociedade Brasileira do Trauma Ortopédico (SBTO), em São Paulo, Brasil, em 4 de novembro de 2022. Métodos: Quarenta e oito cirurgiões de trauma ortopédico de cinco regiões diferentes do Brasil receberam um link para preencher o The Big Five Test, uma avaliação de personalidade on-line validada. O questionário estava disponível em português e pretendia fornecer informações básicas sobre traços de personalidade individuais e sua influência nas interações interpessoais. O PDL integrou conteúdo de análises de literatura específicas da América Latina, e programas de liderança estabelecidos pelas principais escolas de negócios e por vários especialistas no assunto. Antes do início do PDL, os participantes receberam uma pesquisa pré-curso solicitando informações demográficas, uma avaliação de necessidades e a priorização de tópicos de liderança utilizando uma escala Likert de 5 pontos. Os participantes participaram do PDL interativo de um dia com foco nos princípios fundamentais de desenvolvimento de liderança, comunicação, desenvolvimento pessoal, inteligência emocional e negociação. Após o PDL, foi realizada uma avaliação pós-curso para determinar a experiência geral dos participantes e sugestões para melhoria do PDL. Resultados: Quarenta e um dos quarenta e oito participantes do curso concluíram a avaliação pré-curso, enquanto quarenta e seis dos quarenta e oito participantes concluíram a avaliação pós-curso. A falta de oportunidade foi relatada com maior prevalência como o principal obstáculo para frequentar um curso de liderança, conforme citado por 56% dos entrevistados. Conclusão: Expandir a acessibilidade, a diversidade e a personalização dos programas de liderança podem facilitar o desenvolvimento de ferramentas pessoais necessárias para fazer avançar os cuidados de saúde. Os tópicos críticos incluem inteligência emocional e outras qualidades de liderança diferenciadas, que distinguem verdadeiros líderes transformacionais e servidores O avanço das competências de liderança pode estimular o networking, expor os alunos a estilos de aprendizagem experiencial, inspirar outros a criar mudanças positivas e gerar soluções criativas para melhorias sistemáticas dos resultados na saúde. Nível de Evidência III; Estudos de caso-controle individuais.

Cerebrospinal Fluid Shunt Reinfection and Malfunction in Ecuadorian Children with Different Reshunting Criteria After Infection. "Is It Just One Shunt After Another?"

OBJECTIVE: There is no firm evidence regarding cerebrospinal fluid (CSF) shunt reimplantation after infection in the pediatric population. The purpose of this study was to compare different criteria and analyze new shunt failure. METHODS: A cross-sectional retrospective multicenter study was performed over 6 years to study patients and each infected shunt at diagnosis, reimplantation, and after reimplantation. The patients were divided into 2 groups: group 1 (G1), reimplantation after negative serial CSF cultures during antibiotic treatment; group 2 (G2), reimplantation after negative serial pancultures after completion of antibiotics. The differences were measured with Mann-Whitney and Χ2 tests; multivariate analysis and associations were calculated using odds ratios (ORs) based on logistic regression. RESULTS: There were 137 shunt infection events in 110 patients: 28 events in G1 and 109 in G2. Significant differences were observed in the diagnosis and reimplantation. Reimplantation dysfunction in G1 was 16 (55.17%) versus 30 (27.78%) in G2 (P = 0.006). The risk of shunt malfunction after reimplantation increased for G1 reimplantation criteria (P = 0.018; OR, 3.34; confidence interval [CI], 1.23-9.05): pleocytosis at diagnosis >17 cells (P = 0.036; OR, 2.41; CI, 1.06-5.47), CSF proteins at diagnosis >182 mg/dL (P = 0.049; OR, 2.21; CI, 1.00-4.89). CONCLUSIONS: G2 reimplantation criteria were related to improved pleocytosis, CSF proteins, and blood neutrophils compared with G1. Mechanical and infectious dysfunction of the new shunt was 3 times more prevalent in G1 than in G2, considering the differences between the groups at diagnosis. Increased parameters of infection at diagnosis were associated with future malfunction more than parameters before reimplantation in both groups.

Prevalence and Diagnostic Journey of Friedreich's Ataxia in the State of São Paulo, Brazil.

Friedreich's Ataxia (FRDA) is the leading cause of ataxia worldwide, but data on epidemiology and diagnostic journey are scarce, particularly in Latin America. Herein we estimated the prevalence of FRDA in the most populous Brazilian state and characterized the diagnostic odyssey of the disease. We received anonymized data of patients with FRDA from advocacy groups and physicians. Prevalence was estimated dividing the number of patients by the population of the state as reported in the last census. Patients were invited to answer an online survey to describe clinical data and diagnostic journey of the disease. FRDA estimated prevalence was 0.367:100,000, with a slight predominance of women (58.2% vs 41.7%). One hundred and four patients answered the survey (mean age of 37.3 ± 13.8 years; 75.9% classical and 24.0% late onset). On average, 6.2 ± 4.1 physicians were visited before reaching the diagnosis. Mean diagnostic delay was 7.8 ± 6.7 years; no difference between classical and LOFA groups was found. Most of the patients reported unsteadiness and gait abnormalities as the first symptom. Neurologists and orthopedical surgeons were the main specialties first sought by patients. We found a prevalence of 0.36:100,000 for FRDA in the state of São Paulo, Brazil. The disease is characterized by remarkable diagnostic delay, with no relevant differences between classical and LOFA patients.

Vision System for a Forestry Navigation Machine.

This article presents the development of a vision system designed to enhance the autonomous navigation capabilities of robots in complex forest environments. Leveraging RGBD and thermic cameras, specifically the Intel RealSense 435i and FLIR ADK, the system integrates diverse visual sensors with advanced image processing algorithms. This integration enables robots to make real-time decisions, recognize obstacles, and dynamically adjust their trajectories during operation. The article focuses on the architectural aspects of the system, emphasizing the role of sensors and the formulation of algorithms crucial for ensuring safety during robot navigation in challenging forest terrains. Additionally, the article discusses the training of two datasets specifically tailored to forest environments, aiming to evaluate their impact on autonomous navigation. Tests conducted in real forest conditions affirm the effectiveness of the developed vision system. The results underscore the system's pivotal contribution to the autonomous navigation of robots in forest environments.

Microsurgical Resection for Cavernous Malformation of the Uncus: 3D-Operative Video.

Cavernous malformations (CMs) are rare and often oligosymptomatic vascular lesions. The main symptoms include seizure and focal neurologic deficits.1-3 Depending on the symptomatology, location, size, and risk factors for bleeding, like the presence of a developmental venous anomaly, CMs can be highly morbid. Thus surgical resection may be considered. Deep-seated and eloquent CMs, like those in the uncus, can be challenging.4,5 In Video 1, we present a 23-year-old male adult who developed focal seizures (i.e., oral automatisms) after an episode of sudden intense headache 1 year ago. His neurologic examination was unremarkable. The patient consented to the procedure and publication of his image. Nevertheless, his magnetic resonance images showed an uncal 2-cm Zabramski type I CM. We exposed the insula and its limen through a right pterional craniotomy and transsylvian corridor. During the video, we discuss the surgical nuances to access and resect this CM lesion en bloc while preserving important vascular structures and white matter tracts. Postoperative neuroimaging demonstrated total resection. In postoperative day 1, the patient had 1 episode of generalized seizure and evolved with contralateral hemiparesis. The patient had a good recovery and was discharged on postoperative day 21. At the 6-month follow-up, the patient had no new epileptic events and presented complete weakness improvement. Through this minimally invasive and well-known surgical corridor, we preserve the mesial and lateral portion of the temporal lobe, reducing the risk of lesions to the Meyer loop and limbic association area.

Outcomes of ablative therapy and radical treatment for prostate cancer: a systematic review and meta-analysis.

PURPOSE: To compare biochemical recurrence, sexual potency and urinary continence outcomes of ablative therapy and radical treatment (radical prostatectomy or radiotherapy with androgen deprivation therapy). MATERIAL AND METHODS: A systematic review and meta-analysis followed the PRISMA guidelines were performed. We searched MEDLINE/PubMed. Biochemical recurrence at three and five years; incontinence rate (patients who used one pad or more) and erectile dysfunction rate at 12 and 36 months (patients who did not have sufficient erection to achieve sexual intercourse) were evaluated. The Mantel-Haenszel method was applied to estimate the pooled risk difference (RD) in the individual studies for categorical variables. All results were presented as 95% confidence intervals (95%CI). Random effects models were used regardless of the level of heterogeneity (I²). (PROSPERO CRD42022296998). RESULTS: Eight studies comprising 2,677 men with prostate cancer were included. There was no difference in biochemical recurrence between ablative and radical treatments. We observed the same biochemical recurrence between ablative therapy and radical treatment within five years (19.3% vs. 16.8%, respectively; RD 0.07; 95%CI=-0.05, 0.19; I2=68.2%; P=0.08) and continence rate at 12 months (9.2% vs. 31.8%, respectively; RD -0.13; 95%CI, -0.27, 0.01; I2=89%; P=0.32). When focal treatment was analyzed alone, two studies with 582 patients found higher erectile function at 12 months in the ablative therapy group than in the radical treatment (88.9% vs. 30.8%, respectively; RD -0.45; 95%CI -0.84, -0.05; I2=93%; P=0.03). CONCLUSION: Biochemical recurrence and urinary continence outcomes of ablative therapy and radical treatment were similar. Ablative therapy appears to have a high rate of sexual potency.

Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions.

Guanylate binding proteins (GBPs) are an evolutionarily ancient family of proteins that are widely distributed among eukaryotes. They belong to the dynamin superfamily of GTPases, and their expression can be partially induced by interferons (IFNs). GBPs are involved in the cell-autonomous innate immune response against bacterial, parasitic and viral infections. Evolutionary studies have shown that GBPs exhibit a pattern of gene gain and loss events, indicative for the birth-and-death model of evolution. Most species harbor large GBP gene clusters that encode multiple paralogs. Previous functional and in-depth evolutionary studies have mainly focused on murine and human GBPs. Since rabbits are another important model system for studying human diseases, we focus here on lagomorphs to broaden our understanding of the multifunctional GBP protein family by conducting evolutionary analyses and performing a molecular and functional characterization of rabbit GBPs. We observed that lagomorphs lack GBP3, 6 and 7. Furthermore, Leporidae experienced a loss of GBP2, a unique duplication of GBP5 and a massive expansion of GBP4. Gene expression analysis by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and transcriptome data revealed that leporid GBP expression varied across tissues. Overexpressed rabbit GBPs localized either uniformly and/or discretely to the cytoplasm and/or to the nucleus. Oryctolagus cuniculus (oc)GBP5L1 and rarely ocGBP5L2 were an exception, colocalizing with the trans-Golgi network (TGN). In addition, four ocGBPs were IFN-inducible and only ocGBP5L2 inhibited furin activity. In conclusion, from an evolutionary perspective, lagomorph GBPs experienced multiple gain and loss events, and the molecular and functional characteristics of ocGBP suggest a role in innate immunity.

Intermediate conduction velocity in two cases of Charcot-Marie-Tooth disease type 1A.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most prevalent hereditary neuropathy worldwide and classically has slow nerve conduction velocity (NCV), in most cases below 38 m/s. Two unrelated patients with motor NCVs in the upper limbs above 38 m/s are reported. METHOD: Case report. RESULTS: Two genetically confirmed CMT1A patients are presented, from two unrelated families (one of British origin and the other of Brazilian origin). Both individuals had upper limb motor NCVs above 38 m/s, with values ranging from 41.9 to 45 m/s in the median nerve and from 42 to 42.3 m/s in the ulnar nerve. They presented with a very mild phenotype, with CMT Neuropathy Score version 2 (CMTNSv2) of 6 and 5, respectively. In contrast, affected family members within both kinships exhibited a classical phenotype with more severe disease manifestation (CMTNSv2 ranging from 12 to 20) and motor NCVs below 30 m/s. CONCLUSION: These cases, although very rare, highlight the importance of testing PMP22 duplication in patients with intermediate conduction velocities.

Symptomatic gallstone disease: Recurrence patterns and risk factors for relapse after first admission, the RELAPSTONE study.

BACKGROUND: Delayed cholecystectomy in patients with symptomatic gallstone disease is associated with recurrence. Limited data on the recurrence patterns and the factors that determine them are available. OBJECTIVE: We aimed to determine the pattern of relapse in each symptomatic gallstone disease (acute pancreatitis, cholecystitis, cholangitis, symptomatic choledocholithiasis, and biliary colic) and determine the associated factors. METHODS: RELAPSTONE was an international multicenter retrospective cohort study. Patients (n = 3016) from 18 tertiary centers who suffered a first episode of symptomatic gallstone disease from 2018 to 2020 and had not undergone cholecystectomy during admission were included. The main outcome was relapse-free survival. Kaplan-Meier curves were used in the bivariate analysis. Multivariable Cox regression models were used to identify prognostic factors associated with relapses. RESULTS: Mean age was 76.6 [IQR: 59.7-84.1], and 51% were male. The median follow-up was 5.3 months [IQR 2.1-12.4]. Relapse-free survival was 0.79 (95% CI: 0.77-0.80) at 3 months, 0.71 (95% CI: 0.69-0.73) at 6 months, and 0.63 (95% CI: 0.61-0.65) at 12 months. In multivariable analysis, older age (HR = 0.57; 95% CI: 0.49-0.66), sphincterotomy (HR = 0.58, 95% CI: 0.49-0.68) and higher leukocyte count (HR = 0.79; 95% CI: 0.70-0.90) were independently associated with lower risk of relapse, whereas higher levels of alanine aminotransferase (HR = 1.22; 95% CI: 1.02-1.46) and multiple cholelithiasis (HR = 1.19, 95% CI: 1.05-1.34) were associated with higher relapse rates. CONCLUSION: The relapse rate is high and different in each symptomatic gallstone disease. Our independent predictors could be useful for prioritizing patients on the waiting list for cholecystectomies.

Standing on shoulder of giants: the incredible legacy of the Judet family in orthopaedic surgery.

In orthopaedic surgery, as well as other areas in medicine, it is common for a surgical technique to carry the original authors' name describing the procedure. The Judet family represents a unique history, since several orthopaedic procedures are known as "Judet's technique". The aim of this historic review is to outline the genealogy of the orthopaedic arm of the Judet family, while crediting each surgical procedure to the specific family member that described the technique.

Highly crystalline and fluorescent BODIPY-labelled phenyl-triazole-coumarins as n-type semiconducting materials for OFET devices.

In this work, the synthesis of BODIPY-phenyl-triazole labelled coumarins (BPhTCs) using a two-step approach is described. The influence of the BODIPY appending on the photophysical, electrochemical and thermal properties of the phenyl-triazole-coumarin precursors (PhTCs) was investigated. Band gap energies were measured by absorption spectroscopy (2.20 ± 0.02 eV in the solid and 2.35 ± 0.01 eV in solution) and cyclic voltammetry (2.10 ± 0.05 eV). The results are supported by DFT calculations confirming the presence of lowest LUMO levels that facilitate the electron injection and stabilize the electron transport. Their charge-transport parameters were measured in Organic Field-Effect Transistor (OFET) devices. BPhTCs showed an ambipolar transistor behavior with good n-type charge mobilities (10-2 cm2V-1s-1) allowing these derivatives to be employed as promising semiconducting crystalline and fluorescent materials with good thermal and air stability up to 250 °C.

Genetic diversity in hereditary axonal neuropathy: Analyzing 53 Brazilian children.

BACKGROUND AND AIMS: The genetic epidemiology of inherited neuropathies in children remains largely unknown. In this study, we specifically investigated the genetic profile of a Brazilian cohort of pediatric patients with pure or complex axonal neuropathies, a crucial knowledge in the near future for establishing treatment priorities and perspectives for this group of patients. METHODS: Fifty-three pediatric patients who were assessed prior to reaching the age of 20, and who had clinical diagnoses of axonal hereditary neuropathy or presented with axonal neuropathy as the primary clinical feature, were included in the study. The recruitment of these cases took place from January 1, 2018, to December 31, 2020. The diagnosis was based on clinical and electrophysiological data. A molecular assessment was made using target-gene panel or whole-exome sequencing. Subsequently, segregation analysis was performed on available family members, and all candidate variants found were confirmed through Sanger. RESULTS: A molecular diagnosis was reached in 68% of the patients (n = 36/53), considering only pathogenic and probably pathogenic variants. Variants in MFN2 (n = 15) and GJB1 (n = 3) accounted for half of the genetically confirmed patients (50%; n = 18/36). The other 18 genetically diagnosed patients had variants in several less common genes. INTERPRETATION: Apart from MFN2 and GJB1 genes, universally recognized as a frequent cause of axonal neuropathies in most studied population, our Brazilian cohort of children with axonal neuropathies showed an important genetic heterogeneity, probably reflecting the multi ethnicity of the Brazilian population. Diagnostic, counseling, and future interventions should consider this characteristic.

Chronic obstructive pulmonary disease mortality in Spain between 1999 and 2019 / Mortalidad por enfermedad pulmonar obstructiva crónica en España entre 1999 y 2019

Introduction Mortality from COPD has decreased in Spain in recent years, but it is unknown whether this decline has been homogeneous among the different regions. Methods From the Statistical Portal of the Ministry of Health of Spain we obtained the age-adjusted mortality rates/100,000 inhabitants for men and women in Spain and the Autonomous Communities for the years 1999–2019, using the coding of the International Classification of Diseases (ICD 10, sections J40–J44). With the adjusted rates we performed a jointpoint regression analysis to estimate an annual percentage change (APC), as well as identify possible points of trend change. Statistical significance was considered for a value of p<0.05. Results During the study period, COPD mortality rates adjusted in Spain decreased from 28.77 deaths/100,000 inhabitants in 1999 to 12.14 deaths/100,000 inhabitants in 2019. We observed a linear decline in COPD mortality in men at national level of −3.67% per year (95% CI −4.1 to −3.4; p<0.001), with differences between the Autonomous Communities. Mortality in women also experienced a decrease in mortality in two phases, with a first period from 1999 to 2006 with a fall of −6.8% per year (95% CI −8.6 to −5.0; p<0.001) and a second period from 2006 to 2019 with a decrease in mortality of −2.1% (95% CI −2.8 to −1.3; p<0.001), with again differences between the Autonomous Communities. Conclusion Mortality rates from COPD have decreased heterogeneously among the different Autonomous Communities in both men and women (AU)

Introducción La mortalidad por EPOC ha disminuido en España en los últimos años, pero se desconoce si esta caída ha sido homogénea entre las diferentes comunidades autónomas. Metodología consultando el Portal Estadístico del Ministerio de Sanidad de España obtuvimos las tasas ajustadas por edad/100.000 habitantes para hombres y mujeres de España y las CCAA para los años 1999 a 2019, utilizando la codificación de la Clasificación Internacional de Enfermedades (CIE 10, secciones J40 a J44). Con las tasas ajustadas realizamos un análisis de regresión de jointpoint con el objetivo de estimar un porcentaje anual de cambio (APC), así como identificar posibles puntos de cambio de tendencia. Se consideró la significación estadística para un valor de p<0.05. Resultados Durante el periodo de estudio, las tasas de mortalidad global ajustada por EPOC en España pasaron de 28.77 muertes/100.000 habitantes en 1999 a 12.14 muertes/100.000 habitantes en 2019. Observamos una caída de la mortalidad por EPOC en varones a nivel de España lineal del -3.67% anual (IC 95% -4.1 a -3.4; p<0.001), con diferencias entre las CCAA. La mortalidad en mujeres también experimentó una disminución de mortalidad en dos fases, con un primer periodo de 1999 a 2006 con caída del -6.8% anual (IC 95% -8.6 a -5.0; p<0.001) y un segundo periodo de 2006 a 2019 con un descenso de la mortalidad del -2.1% (IC 95% -2.8 a -1.3; p<0.001), encontrando diferencias entre las CCAA. Conclusiones Las tasas de mortalidad por EPOC han disminuido de forma heterogénea entre las diferentes CCAA (AU)

Development and evaluation of the in vitro schistosomicidal activity of solid dispersions based on 2-(-5-bromo-1-H-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide.

Among all the neglected diseases, schistosomiasis is considered the second most important parasitic infection after malaria. Praziquantel is the most widely used drug for this disease, but its exclusive use may result in the development of drug-resistant schistosomiasis. To increase the control of the disease, new drugs have been developed as alternative treatments, among them 2-(-5-bromo-1-h-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide (LQIT/LT-50), which showed promising schistosomicidal activity in nonclinical studies. However, LQIT/LT-50 presents low solubility in water, resulting in reduced bioavailability. To overcome this solubility problem, the present study aimed to develop LQIT/LT-50 solid dispersions for the treatment of schistosomiasis. Solid dispersions were prepared through the solvent method using Soluplus©, polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP K-30) as hydrophilic carriers. The formulations with the best results in the compatibility tests, aqueous solubility and preliminary stability studies have undergone solubility tests and physicochemical characterizations by Fourier-transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), exploratory differential calorimetry (DSC), thermogravimetry (TG) and Raman spectroscopy. Finally, the schistosomicidal activity was evaluated in vitro. The phycochemical analyzes showed that when using PVP K-30, there was an interaction between the PVP K-30 and LQIT/LT-50, proving the successful development of the solid dispersion. Furthermore, an increase in the solubility of the new system was observed (LQIT/LT-50:PVP K-30) in addition to the improvement in the in vitro shistosomidal activity at 1:4 (w/w) molar ratio (i.e., 20% drug loading) when compared to LQIT/LT-50 alone. The development of the LQIT/LT-50:PVP K-30 1:4 solid dispersion is encouraging for the future development of new pharmaceutical solid formulations, aiming the schistosomicidal treatment.

All-cause mortality and risk factors in patients with type 1 diabetes in Castilla-La Mancha, Spain. DIACAM1 2010-2020 study.

INTRODUCTION: Despite better treatments and care for patients with type 1 diabetes (T1DM), all-cause and cardiovascular mortality still remains higher compared to the general population. We evaluated mortality and risk factors for mortality in a representative cohort of patients with T1DM. METHODS: DIACAM1 was a cross-sectional, multicenter study on adult patients (≥ 16 years old) and diabetes with at least 5 years since diabetes diagnosis conducted between 2009 and 2010. DIACAM1 2010-2020 study was a follow-up study, extension of DIACAM1, where vital status of patients was evaluated between June 2019 and June 2020. RESULTS: 4.03% [CI95%, 2.53-5.62) of the 1465 patients with T1DM included in the cohort of the DIACAM1 in 2010 had died. Survival was lower than in the sex- and age-matched general population in the same region. 40.7% of deaths were due to cardiovascular disease. HbA1c levels < 7% and triglyceride levels < 150 mg/dL were associated with lower mortality, whereas retinopathy and plasma creatinine were associated with increased mortality. CONCLUSIONS: We confirmed a lower survival in people with T1DM, with cardiovascular disease being the main cause of mortality. High HbA1c, high triglycerides, retinopathy, and high creatinine are factors associated with mortality.

Chronic obstructive pulmonary disease mortality in Spain between 1999 and 2019.

INTRODUCTION: Mortality from COPD has decreased in Spain in recent years, but it is unknown whether this decline has been homogeneous among the different regions. METHODS: From the Statistical Portal of the Ministry of Health of Spain we obtained the age-adjusted mortality rates/100,000 inhabitants for men and women in Spain and the Autonomous Communities for the years 1999-2019, using the coding of the International Classification of Diseases (ICD 10, sections J40-J44). With the adjusted rates we performed a jointpoint regression analysis to estimate an annual percentage change (APC), as well as identify possible points of trend change. Statistical significance was considered for a value of p<0.05. RESULTS: During the study period, COPD mortality rates adjusted in Spain decreased from 28.77 deaths/100,000 inhabitants in 1999 to 12.14 deaths/100,000 inhabitants in 2019. We observed a linear decline in COPD mortality in men at national level of -3.67% per year (95% CI -4.1 to -3.4; p<0.001), with differences between the Autonomous Communities. Mortality in women also experienced a decrease in mortality in two phases, with a first period from 1999 to 2006 with a fall of -6.8% per year (95% CI -8.6 to -5.0; p<0.001) and a second period from 2006 to 2019 with a decrease in mortality of -2.1% (95% CI -2.8 to -1.3; p<0.001), with again differences between the Autonomous Communities. CONCLUSION: Mortality rates from COPD have decreased heterogeneously among the different Autonomous Communities in both men and women.

A novel metalloproteinase-derived cryptide from Bothrops cotiara venom inhibits angiotensin-converting enzyme activity.

Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara, including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin. Using FRET (fluorescence resonance energy transfer) substrate assays, we demonstrated that Bc-7a strongly inhibits the two domains of angiotensin converting enzyme (Ki < 1 µM). Our findings contribute to the repertoire of biologically active peptides from snake venoms capable of inhibiting angiotensin-converting enzyme (ACE), beyond current known structural motifs and precursors. In summary, we report a novel snake venom peptide with ACE inhibitory activity, suggesting its potential contribution to the hypotensive effect observed in envenomation.