Efficacy of short-course treatment for prevention of congenital transmission of Chagas disease: A retrospective cohort study.

BACKGROUND: In regions with controlled vector transmission of T. cruzi, congenital transmission is the most frequent route of infection. Treatment with benznidazole (BZ) or nifurtimox (NF) for 60 days in girls and women of childbearing age showed to be effective in preventing mother to child transmission of this disease. Reports on short-course treatment (≤30 days) are scarce. METHODS: Retrospective cohort study. Offspring of women with Chagas disease who received short-course treatment (≤30 days) with BZ or NF, attended between 2003 and 2022, were evaluated. Parasitemia (microhaematocrit and/or PCR) was performed at <8 months of age, and serology (ELISA and IHA) at ≥8 months to rule out congenital infection. RESULTS: A total of 27 women receiving ≤30 days of treatment and their children were included in this study. NF was prescribed in 17/27 (63%) women, and BZ in 10/27 (37%). The mean duration of treatment was 29.2 days. None of the women experienced serious adverse events during treatment, and no laboratory abnormalities were observed. Forty infants born to these 27 treated women were included. All newborns were full term, with appropriate weight for their gestational age. No perinatal infectious diseases or complications were observed. DISCUSSION: Several studies have shown that treatment of infected girls and women of childbearing age for 60 days is an effective practice to prevent transplacental transmission of T. cruzi. Our study demonstrated that short-duration treatment (≤30 days) is effective and beneficial in preventing transplacental transmission of Chagas disease.

Venopulmonary Artery Extracorporeal Life Support (VPa ECMO): A Novel Strategy for Refractory Hypoxemia Complicating VV ECMO.

Refractory hypoxemia (RH) during venovenous extracorporeal membrane oxygenation (VV ECMO) support is a complex problem that limits the benefit of this therapy. The need for sustained deep sedation and delays in active rehabilitation are considered as a direct consequence of RH. Changing from VV ECMO to a configuration that returns the flow to pulmonary artery, such as venopulmonary extracorporeal membrane oxygenation (VPa ECMO) may decrease recirculation and improve systemic oxygen delivery. We present a retrospective report that describes the impact of VPa ECMO on oxygenation during sedation withdrawal in 41 patients who received VV ECMO for coronavirus disease 2019 (COVID-19). We evidenced that arterial oxygen pressure (PaO 2 ) increased from 68 to 112.3 mm Hg ( p = 0.001) with a reduction of ECMO flow (5.7-4.8 L/m; p = 0.001). Other findings included lower rates of depth sedation (Richmond Agitation Sedation Scale [RASS] ≤3, 37-63%; p = 0.007) and lower requirement inotropic support assessed by LVIS score (4.7-1.1; p = 0.005). Discharge survival was 54% with a sustained benefit until day 79. This cannulation strategy improved effectively PaO 2 in this cohort, it may be an alternative in patients with RH in VV ECMO.

Soft skills in personnel training: Report of publications in scopus, topics explored and future research agenda.

Recent research has documented the interest of organizations in training their staff in soft skills, but few studies have been found. Therefore, the objective of this research was to analyze 753 publications in the Scopus database related to soft skills in staff training during the period 1999-2021. These documents were analyzed to identify the main information, the most explored areas, and a future research agenda; all under a bibliometric and bibliographic approach with the help of RStudio and VOSviewer software. The results showed that the keywords with the most co-occurrence were personnel training (n = 110) and soft skills (n = 79). The year with the most documents was 2021 (n = 121). The country with the most publications was the United Kingdom (n = 199). Medicine is the subject area with the most documents (n = 278) and the Article is the type of document with the most studies (n = 566). Eleven areas of further exploration were identified: "Soft skills in software engineering at the higher education level", "Soft skills and communication", "Soft skills and engineering education", "Soft skills in virtual environments", "Soft skills in machine learning", "Serious games in teaching soft skills", "Soft skills for problem-based learning", "Soft skills for project management", "Soft skills and technical skills", "Project-based learning for the assessment of soft skills" and "Soft leadership skills". Five potential areas for future research were derived: soft skills in collaborative work (CSCL), soft skills in computer-aided collaborative work (CSCW), facial expressions as a mirror of soft skills, soft skills for employability and Professional Development Plan (PDP) to assess soft skills. In conclusion, this Review type document on soft skills in personnel training helped to identify the most studied topics during the evaluated period, as well as to identify the little explored topics for future research.

Biomecánica del pase con borde interno entre futbolistas prejuveniles y juveniles de Formativas y Academia / Biomecânica do passe com bordo interior entre os jogadores de futebol pré-juvenil e juvenil de formação e academia / Biomechanics of the pass with internal edge among prejuvenile and juvenile soccer players of Formative and Academy centers

RESUMEN La biomecánica es una ciencia que ayuda al estudio de los movimientos aplicados en distintos deportes, incluyendo el fútbol, que permite identificar y corregir errores técnicos. Esta es una base fundamental para el control de la preparación del deportista. En tal sentido, se planteó como propósito de la investigación analizar biomecánicamente el pase con borde interno del pie en futbolistas prejuveniles y juveniles de Formativas y Academia. La investigación es de tipo descriptiva-explicativa, de orden correlacional; se diagnostican biomecánicamente a 40 futbolistas en dos grupos independientes (grupo 1: Formativas; grupo 2: Academia; entre 14-18 años). Se analizan diez indicadores, se incluye la edad. Se demostraron diferencias significativas en el indicador "DB" (p=0.000), el indicador "ÁFRA" (p=0.006), el indicador "DPAE" (p=0.000), y los indicadores "VF", "A" y "TE" (p=0.000) respectivamente, mientras que las variables o indicadores "ÁFRE" (p=1.000), "EX" (p=0.102) y "EY" (p=0.056) no presentaron diferencias significativas entre los grupos independientes. En la comparación realizada con los jugadores de un equipo profesional y los jugadores de una Academia de formación, se pudo evidenciar que existen diferencias notables desde la fase inicial del pase con el borde interno del pie, mostrando la distancia del jugador con respecto al balón, así como en la fase previa donde los jugadores de Formativas poseen una mejor ejecución del movimiento técnico; esto se refleja en la fase de contacto donde se evidencia una mayor velocidad y aceleración al momento del impacto con el balón.

RESUMO A biomecânica é uma ciência que ajuda o estudo dos movimentos aplicados em diferentes desportos, incluindo o futebol, o que permite a identificação e correção de erros técnicos. Esta é uma base fundamental para o controlo da preparação do atleta. Neste sentido, o objectivo da investigação era analisar biomecanicamente o passe com a extremidade interna do pé em jogadores de futebol pré-juvenil e juvenil em treino e academia. A investigação é de tipo descritivo-explicativo, de ordem correlativa; 40 jogadores de futebol são diagnosticados biomecanicamente em dois grupos independentes (Grupo 1: Formação; Grupo 2: Academia; entre 14-18 anos de idade). Foram analisados dez indicadores, incluindo a idade. Foram demonstradas diferenças significativas no indicador "DB" (p=0,000), o indicador "ÁFRA" (p=0,006), o indicador "DPAE" (p=0,000), e os indicadores "VF", "A" e "TE" (p=0,000) respectivamente, enquanto que as variáveis ou indicadores "ÁFRE" (p=1,000), "EX" (p=0,102) e "EY" (p=0,056) não apresentavam diferenças significativas entre os grupos independentes. Na comparação feita com os jogadores de uma equipa profissional e com os jogadores de uma academia de treino, constatou-se que existem diferenças notáveis em relação à fase inicial do passe com a borda interior do pé, mostrando a distância do jogador em relação à bola, bem como na fase anterior em que os jogadores da academia de treino têm uma melhor execução do movimento técnico; isto reflete-se na fase de contato onde é evidente uma maior velocidade e aceleração no momento do impacto com a bola.

ABSTRACT Biomechanics is a science that helps the study of movements applied in different sports, including soccer, which allows identifying and correcting technical errors. This is a fundamental basis for the control of the athlete's preparation. In this sense, the purpose of the research was to analyze biomechanically the pass with the inner edge of the foot in pre-juvenile and youth soccer players of training and academy. The research is of descriptive-explanatory type, of correlational order; 40 soccer players were biomechanically diagnosed in two independent groups (Group 1: Formative; Group 2: Academy; between 14-18 years). Ten indicators are analyzed, including age. Significant differences were demonstrated in the "DB" indicator (p=0.000), the "ÁFRA" indicator (p=0.006), the "DPAE" indicator (p=0.000), and the "VF", "A" and " TE" (p=0.000) respectively, while the variables or indicators "ÁFRE" (p=1.000), "EX" (p=0.102) and "EY" (p=0.056) did not present significant differences between the independent groups. In the comparison made with the players of a professional team and the players of a training academy, it was possible to show that there are notable differences from the initial phase of the pass with the inner edge of the foot, showing the distance of the player with respect to the ball, as well as in the previous phase where the players in formatiom have a better execution of the technical movement; this is reflected in the contact phase where greater speed and acceleration are evident at the moment of impact with the ball.

Diferencias biomecánicas entre jugadores avanzados y amateur en la ejecución del tiro libre en fútbol / Diferenças biomecânicas entre jogadores avançados e amadores na execução do pontapé livre no futebol / Biomechanical differences between advanced and amateur players in the execution of the free kick in soccer

RESUMEN El tiro libre en el fútbol es una de las técnicas deportivas de importancia, la cual permite reanudar el juego luego de la falta cometida por el otro jugador. La potenciación de la habilidad motriz específica permite desarrollar mayores rendimientos a corto y largo plazo, por lo cual su caracterización es importante para desarrollar metodologías especializadas en las etapas de iniciación deportiva. En tal sentido, la presente investigación tuvo por objetivo analizar las diferencias biomecánicas del tiro libre entre jugadores avanzados y amateur de fútbol. Este estudio es de tipo descriptivo-explicativo de orden correlacional, se diagnostican intencionalmente a 30 futbolistas de la Escuela de Fútbol Chiqui Park (16-32 años de edad), clasificados en dos grupos independientes, el grupo 1 con futbolistas avanzados, y el grupo 2 con futbolistas de nivel amateur. Se evalúan tres variables: el ángulo inicial de la Fase unipodal (AIFU), el ángulo final de la fase final (AFF), y el tiempo de ejecución del tiro libre (TE). No se evidencian diferencias significativas entre grupos independientes en las variables angulares AIFU (p=0.683) y AFF (p=0.389), y una diferencia significativa a favor del grupo 2 en la variable TE (p=0.000). Sin embargo, todos los rangos promedios favorecieron a los futbolistas de nivel avanzado. Existe la necesidad de establecer integralmente mayores estudios que caractericen las categorías formativas estudiadas, sirviendo de base teórica y metodología que fundamente el desarrollo de acciones técnico-tácticas y físicas de consideración en los procesos de dirección del entrenamiento deportivo.

RESUMO O pontapé livre no futebol é uma das técnicas desportivas mais importantes, que permite o reinício do jogo após uma falta cometida pelo outro jogador. A potenciação da habilidade motora específica permite o desenvolvimento de desempenhos mais elevados a curto e longo prazo, razão pela qual a sua caracterização é importante para desenvolver metodologias especializadas nas fases de iniciação ao desporto. Neste sentido, o objectivo desta investigação era analisar as diferenças biomecânicas do pontapé livre entre jogadores de futebol avançados e amadores. Este estudo é de um tipo descritivo-explicativo de ordem correlacional, 30 jogadores de futebol da Escola de Futebol do Chiqui Park (16-32 anos de idade) são intencionalmente diagnosticados, classificados em dois grupos independentes, grupo 1 com jogadores de futebol avançados, e grupo 2 com jogadores de futebol amadores. São avaliados os seguintes São avaliadas três variáveis de interesse: o ângulo inicial da fase unipodal (AIFU), o ângulo final da fase final (AFF), e o tempo de execução do lançamento livre (TE). Não foram evidentes diferenças significativas entre grupos independentes nas variáveis angulares AIFU (p=0,683) e AFF (p=0,389), e uma diferença significativa a favor do grupo 2 na variável TE (p=0,000). No entanto, todas as gamas médias favoreceram os jogadores de nível avançado. Há necessidade de estabelecer de forma abrangente outros estudos que caracterizem as categorias de formação estudadas, servindo como base teórica e metodológica para o desenvolvimento de ações técnico-tácticas e físicas de consideração nos processos de gestão da formação desportiva.

ABSTRACT The free kick in soccer is one of the important sports techniques, which allows the game to resume after a foul committed by the other player. The enhancement of specific motor skills allows the development of higher performance in the short and long term, for which its characterization is important to develop specialized methodologies in the stages of sports initiation. In this sense, the present research aimed to analyze the biomechanical differences of the free kick between advanced and amateur soccer players. This study is of a descriptive-explanatory type of correlational order, 30 soccer players from the Chiqui Park Soccer School (16-32 years of age) are intentionally diagnosed, classified into two independent groups, group 1 with advanced soccer players, and group 2 with amateur level soccerers. Three variables of interest are evaluated: the Initial Angle of the Unipodal Phase (AIFU in Spanish), the Final Angle of the Final Phase (AFF in Spanish), and the Execution Time of the Free Throw (TE in Spanish). There are no significant differences between independent groups in the angular variables AIFU (p=0.683) and AFF (p=0.389), and a significant difference in favor of group 2 in the variable TE (p=0.000). However, all the average ranges favored the advanced level players. There is a need to comprehensively establish larger studies that characterize the training categories studied, serving as a theoretical basis and methodology that supports the development of technical-tactical and physical actions of consideration in the processes of sports training management.

Genetic polymorphism of Trypanosoma cruzi bloodstream populations in adult chronic indeterminate Chagas disease patients from the E1224 clinical trial.

BACKGROUND: The role that the genetic diversity of natural Trypanosoma cruzi populations plays in response to trypanocidal treatment of chronic Chagas disease (CD) patients remains to be understood. We analysed the genetic polymorphisms of parasite bloodstream populations infecting chronic CD patients enrolled in the E1224 clinical trial. METHODS: A total of 506 baseline and post-treatment follow-up samples from 188 patients were analysed. T. cruzi satellite DNA (satDNA) was amplified and sequenced using cruzi1/cruzi2 primers, and samples with TcI/III, TcII, TcIV or hybrid satDNA sequences were identified. Minicircle signatures were obtained after kinetoplast DNA amplification using 121/122 primers and restriction enzyme digestion. Genetic distances between baseline and post-treatment minicircle signatures were estimated using the Jaccard coefficient. RESULTS: At baseline, 74.3% TcII, 17.9% hybrid and 7.8% TcI/III satDNA sequences were found, whereas at the end of follow-up the distribution was 55.2% TcII, 35.2% hybrid and 9.5% TcI/III. The placebo arm was the treatment group with the highest variation of satDNA sequences between baseline and post-treatment follow-up. Genetic distances between baseline and post-treatment minicircle signatures were similar among all treatment arms. No association between minicircle signature variability and satDNA type distribution was found. CONCLUSIONS: Genetic variability of T. cruzi bloodstream populations during post-treatment follow-up did not differ from that observed during chronic infection in the absence of treatment, suggesting that there were no selection events of E1224-resistant parasite populations. This is the first report documenting the genetic polymorphism of natural T. cruzi populations in chronic patients in the context of clinical trials with trypanocidal drugs.

Abordaje mínimamente invasivo del tumor de Wilms unilateral: un reporte de caso y revisión de la literatura / Minimally invasive approach to unilateral Wilms tumor: a case report and literature review

Introducción. El tumor de Wilms es la neoplasia abdominal más común en pacientes pediátricos. En la mayoría de los casos se presenta como una masa unilateral indolora en el abdomen. El objetivo de este artículo fue presentar el caso de una paciente de 4 años con tumor de Wilms unilateral derecho manejado con cirugía mínimamente invasiva en el Hospital Universitario del Valle. Métodos. Revisión de la historia clínica e imágenes de la paciente, descripción de la técnica quirúrgica y revisión de la literatura del manejo de tumor de Wilms unilateral. Caso clínico. Paciente femenina de 4 años quien consultó en abril de 2019 por un cuadro clínico de dolor abdominal y sensación de masa en flanco derecho. Se realizó ecografía abdominal donde se encontró imagen nodular heterogénea de contornos definidos en riñón derecho, con riñón izquierdo normal. Se hizo diagnóstico de tumor de Wilms unilateral y se llevó a cirugía mediante abordaje mínimamente invasivo, con buena evolución postoperatoria. Conclusión. La cirugía es el pilar del manejo, y la nefrectomía mediante abordaje laparoscópico para casos seleccionados, en manos entrenadas, tiene la suficiente eficacia, seguridad y cumplimiento de los principios quirúrgicos y oncológicos que provee la cirugía abierta.

Introduction. Wilms tumor is the most common abdominal neoplasm in pediatric patients. In most cases it presents as a painless unilateral mass in the abdomen. The objective of this article was to present the case of a 4-year-old patient with right unilateral Wilms tumor managed with minimally invasive surgery at the Hospital Universitario del Valle. Methods. Review of the patient's clinical history and images, description of the surgical technique and review of the literature on the management of unilateral Wilms tumor.Clinical case. A 4-year-old female patient who consulted on April 4, 2019 with a clinical presentation of abdominal pain and sensation of mass in the right flank. Abdominal ultrasound was performed where a heterogeneous nodular image of defined contours was found in the right kidney, with a normal left kidney. A diagnosis of unilateral Wilms tumor was made and surgery was carried out using a minimally invasive approach, with good postoperative evolution. Conclusion. Wilms tumor is the most common abdominal neoplasm in pediatric patients. The most common presentation is a painless palpable mass. Surgery is the mainstay of management, and nephrectomy using a laparoscopic approach for selected cases, in trained hands, has sufficient efficacy, safety, and compliance with surgical and oncological principles that open surgery provides.

Molecular Imaging of Vulnerable Coronary Plaque with Radiolabeled Somatostatin Receptors (SSTR).

Atherosclerosis is responsible for the majority of heart attacks and is characterized by several modifications of the arterial wall including an inflammatory reaction. The silent course of atherosclerosis has made it necessary to develop predictors of disease complications before symptomatic lesions occur. Vulnerable to rupture atherosclerotic plaques are the target for molecular imaging. To this aim, different radiopharmaceuticals for PET/CT have emerged for the identification of high-risk plaques, with high specificity for the identification of the cellular components and pathophysiological status of plaques. By targeting specific receptors on activated macrophages in high-risk plaques, radiolabelled somatostatin analogues such as 68Ga-DOTA-TOC, TATE,0 or NOC have shown high relevance to detect vulnerable, atherosclerotic plaques. This PET radiopharmaceutical has been tested in several pre-clinical and clinical studies, as reviewed here, showing an important correlation with other risk factors.

Manejo quirúrgico de prolapso uretral en pediatría: Reporte de caso / Surgical management of urethral prolapse in pediatrics: A case report

Introducción. El prolapso uretral es una entidad poco común, con una incidencia estimada de 1 en 3000 mujeres. Se presenta cuando la mucosa uretral sobresale espontáneamente más allá del meato uretral. Es una patología poco diagnosticada dada su baja frecuencia y de allí la importancia de conocer sobre su presentación, diagnóstico y tratamiento. El objetivo de este artículo fue presentar el caso de una paciente de 10 años con diagnóstico de prolapso uretral y su manejo quirúrgico. Caso clínico. Paciente femenina de 10 años, que consultó por cuadro clínico de 1 año de evolución consistente en dolor en región urogenital, que se irradiaba a hipogastrio, asociado a pujo y disuria, a quien se le diagnosticó prolapso uretral y se realizó corrección quirúrgica de mucosa uretral prolapsada mediante técnica de Kelly-Burnham modificada. Conclusión. El prolapso uretral es una entidad que con frecuencia es diagnosticada erróneamente pues su diagnóstico es eminentemente clínico. Si bien se ha descrito el tratamiento médico en primera instancia, éste tiene una alta tasa de recurrencia, por lo que en estos casos se prefiere la resección quirúrgica del tejido prolapsado.

Introduction. Urethral prolapse is a rare entity, with an estimated incidence of 1 in 3,000 women. It occurs when the urethral mucosa spontaneously protrudes beyond the urethral meatus. It is a poorly diagnosed pathology given its low frequency and hence the importance of knowing about its presentation, diagnosis and treatment. The objective of this article was to present the case of a 10-year-old patient with a diagnosis of urethral prolapse and its surgical management. Clinical case. A 10-year-old female patient, who consulted for a 1-year clinical picture consisting of pain in the urogenital region, radiating to the hypogastrium, associated with pushing and dysuria, who was diagnosed with urethral prolapse and a surgical correction of the urethral mucosa was performed prolapsed by modified Kelly-Burnham technique. Conclusion. Urethral prolapse is an entity that is frequently misdiagnosed because its diagnosis is eminently clinical. Although medical treatment has been described in the first instance, it has a high recurrence rate, so surgical resection of the prolapsed tissue is preferred in these cases.

Prospective multicenter evaluation of real time PCR Kit prototype for early diagnosis of congenital Chagas disease.

BACKGROUND: Current algorithm for Congenital Chagas Disease (cCD) diagnosis is unsatisfactory due to low sensitivity of the parasitological methods. Moreover, loss to follow-up precludes final serodiagnosis after nine months of life in many cases. A duplex TaqMan qPCR kit for Trypanosoma cruzi DNA amplification was prospectively evaluated in umbilical cord (UCB) and peripheral venous blood (PVB) of infants born to CD mothers at endemic and non-endemic sites of Argentina. METHODS: We enrolled and followed-up 370 infants; qPCR was compared to gold-standard cCD diagnosis following studies of diagnostic accuracy guidelines. FINDINGS: Fourteen infants (3·78%) had cCD. The qPCR sensitivity and specificity were higher in PVB (72·73%, 99·15% respectively) than in UCB (66·67%, 96·3%). Positive and negative predictive values were 80 and 98·73% and 50 and 98·11% for PVB and UCB, respectively. The Areas under the Curve (AUC) of ROC analysis for qPCR and micromethod (MM) were 0·81 and 0·67 in UCB and 0·86 and 0·68 in PVB, respectively. Parasitic loads ranged from 37·5 to 23,709 parasite equivalents/mL. Discrete typing Unit Tc V was identified in five cCD patients and in six other cCD cases no distinction among Tc II, Tc V or Tc VI was achieved. INTERPRETATION: This first prospective field study demonstrated that qPCR was more sensitive than MM for early cCD detection and more accurate in PVB than in UCB. Its use, as an auxiliary diagnostic tool to MM will provide more accurate records on cCD incidence. FUNDING: FITS SALUD 001-CHAGAS (FONARSEC, MINCyT, Argentina) to the Public-Private Consortium (INGEBI-CONICET, INP-ANLIS MALBRAN and Wiener Laboratories); ERANET-LAC-HD 328 to AGS and PICT 2015-0074 (FONCYT, MinCyT) to AGS and FA.

New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial.

BACKGROUND: Current treatment for Chagas disease with the only available drugs, benznidazole or nifurtimox, has substantial limitations, including long treatment duration and safety and tolerability concerns. We aimed to evaluate the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole, in the treatment of Chagas disease. METHODS: We did a double-blind, double-dummy, phase 2, multicentre, randomised trial in three outpatient units in Bolivia. Adults aged 18-50 years with chronic indeterminate Chagas disease, confirmed by serological testing and positive qualitative PCR results, were randomly assigned (1:1:1:1:1:1:1) to one of seven treatment groups using a balanced block randomisation scheme with an interactive response system. Participants were assigned to benznidazole 300 mg daily for 8 weeks, 4 weeks, or 2 weeks, benznidazole 150 mg daily for 4 weeks, benznidazole 150 mg daily for 4 weeks plus fosravuconazole, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, or placebo, with a 12-month follow-up period. The primary endpoints were sustained parasitological clearance at 6 months, defined as persistent negative qualitative PCR results from end of treatment, and incidence and severity of treatment-emergent adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Primary efficacy analysis was based on the intention-to-treat and per-protocol populations and secondary efficacy analyses on the per-protocol population. Safety analyses were based on the as-treated population. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT03378661. FINDINGS: Between Nov 30, 2016, and July 27, 2017, we screened 518 patients, and 210 were enrolled and randomised. 30 patients (14%) were assigned to each treatment group. All 210 randomised patients were included in the intention-to-treat population, and 190 (90%) were included in the per-protocol population. In the intention-to-treat analysis, only one (3%) of 30 patients in the placebo group had sustained parasitological clearance at 6 months of follow-up. Sustained parasitological clearance at 6 months was observed in 25 (89%) of 28 patients receiving benznidazole 300 mg daily for 8 weeks (rate difference vs placebo 86% [95% CI 73-99]), 25 (89%) of 28 receiving benznidazole 300 mg daily for 4 weeks (86% [73-99]), 24 (83%) of 29 receiving benznidazole 300 mg daily for 2 weeks (79% [64-95]), 25 (83%) of 30 receiving benznidazole 150 mg daily for 4 weeks (80% [65-95]), 23 (85%) of 28 receiving benznidazole 150 mg daily for 4 weeks plus fosravuconazole (82% [67-97]), and 24 (83%) of 29 receiving benznidazole 300 mg weekly for 8 weeks plus fosravuconazole (79% [64-95]; p<0·0001 for all group comparisons with placebo). Six patients (3%) had ten serious adverse events (leukopenia [n=3], neutropenia [n=2], pyrexia, maculopapular rash, acute cholecystitis, biliary polyp, and breast cancer), eight had 12 severe adverse events (defined as interfering substantially with the patient's usual functions; elevated alanine aminotransferase [n=4], elevated gamma-glutamyltransferase [n=2], elevated aspartate aminotransferase [n=1], neutropenia [n=3], leukopenia [n=1], and breast cancer [n=1]), and 15 (7%) had adverse events that led to treatment discontinuation (most of these were in the groups who received benznidazole 300 mg daily for 8 weeks, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, and benznidazole 150 mg daily for 4 weeks plus fosravuconazole). No adverse events leading to treatment discontinuation were observed in patients treated with benznidazole 300 mg daily for 2 weeks or placebo. There were no treatment-related deaths. INTERPRETATION: Benznidazole induced effective antiparasitic response, regardless of treatment duration, dose, or combination with fosravuconazole, and was well tolerated in adult patients with chronic Chagas disease. Shorter or reduced regimens of benznidazole could substantially improve treatment tolerability and accessibility, but further studies are needed to confirm these results. FUNDING: Drugs for Neglected Diseases initiative (DNDi). TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: Clinical, Parasitological, and Serological Assessment after Three Years of Follow-Up.

In a pilot study, we showed that the intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by quantitative PCR (qPCR) at the end of treatment. Here, a 3-year posttreatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg of body weight/day in two daily doses every 5 days. Parasite load, Trypanosoma cruzi-specific antibodies, and serum chemokine levels were measured prior to treatment and after a median follow-up of 36 months posttreatment by DNA minicircle kinetoplastid and nuclear DNA satellite sequence qPCR methods, conventional serological techniques, a Luminex-based assay with recombinant T. cruzi proteins, and a cytometric bead array. At the end of follow-up, 14 of 17 (82%) patients had negative qPCR findings, whereas three of 17 (18%) had detectable nonquantifiable findings by at least one of the qPCR techniques. A decline in parasite-specific antibodies at 12 months posttreatment was confirmed by conventional serological tests and the Luminex assays. Monocyte chemoattractant protein 1 levels increased after treatment, whereas monokine induced by gamma interferon levels decreased. New posttreatment electrocardiographic abnormalities were observed in only one patient who had cardiomyopathy prior to treatment. Together, these data strengthen our previous findings by showing that the intermittent administration of benznidazole results in a low rate of treatment suspension, with treatment efficacy comparable to that of a daily dose of 5 mg/kg for 60 days.

Estrategias de educación en un programa de formación en cirugía pediátrica, como respuesta a la pandemia por COVID-19 / Education strategies in a pediatric surgery training program in response to the COVID-19 pandemic

Introducción. La pandemia por COVID-19 ha ocasionado cambios de todo orden en el mundo. Las medidas de emergencia han impactado de manera negativa la oportunidad en la prestación de los servicios de salud y los procesos de educación médica. Los educadores se han visto obligados a innovar y apoyarse mucho más en las tecnologías de la información y la comunicación, con el fin de lograr los objetivos de formación. Objetivo. Describir la implementación de estrategias de enseñanza para hacer frente a los retos que impone la pandemia por COVID-19 en un programa de formación en cirugía pediátrica. Métodos. Revisión de los registros y la asistencia a las actividades académicas programadas antes y después de la llegada del coronavirus a Colombia. Resultados. Como respuesta a la contingencia, y con el apoyo de las tecnologías de la información y la comunicación, se incrementó el número de actividades académicas en un 100 %, se logró duplicar la asistencia a las mismas y la participación de expertos nacionales e internacionales. Conclusión. La nueva normalidad impuesta por la pandemia por COVID-19 exige a los educadores en salud desarrollar estrategias de enseñanza y aprendizaje innovadoras las cuales, con la integración de las tecnologías disponibles, permiten enfrentar las dificultades y cumplir con los objetivos de formación en salud

Introduction. The COVID-19 pandemic has caused changes of all kinds in the world. The emergency measures have negatively affected the opportunity in the provision of health services and the medical education processes. Educators have been forced to innovate and have supported much more on information and communication technologies, in order to achieve the training objectives. Objective. To describe the implementation of teaching strategies to face the challenges posed by the COVID-19 pandemic in a pediatric surgery training program. Methods. Review of records and attendance at scheduled academic activities before and after the arrival of the coronavirus in Colombia. Results. In response to the contingency, and with the support of information and communication technologies, the number of academic activities was increased by 100%, attendance at them was doubled and the participation of national and international experts. Conclusion. The new normal imposed by the COVID-19 pandemic requires health educators to develop inno-vative teaching and learning strategies, which, with the integration of available technologies, make it possible to face difficulties and meet health-training objectives

Evaluación teórica de las propiedades electrónicas y estructurales que afectan a la conductividad eléctrica en copolímeros de furano-tiofeno / Theoretical evaluation of the electronic and structural properties that affect the electrical conductivity in furan-thiophene copolymers / Avaliação teórica das propriedades eletrônicas e estruturais que afetam à condutividade eléctrica em copolímeros de furano-tiofeno

Resumen Desde el punto de vista científico y tecnológico ha habido un gran interés en el uso de monosustituyentes de furano y tiofeno como polímeros conductores, debido a sus múltiples aplicaciones como OLED, amplificadores ópticos, nanotecnología, entre otros. Por ello, el propósito de este trabajo fue estudiar los aspectos teóricos que afectan las propiedades electroconductoras de este tipo de moléculas. Se determinaron teóricamente los aspectos estructurales y electrónicos que influyeron en la conductividad de copolímeros de furano-tiofeno monosustituidos, al utilizar grupos carboxilos, metilos, hidroxilos, ciano y fluoruros como sustituyentes en el carbono C3 y C10 de cada heterociclo. La diferencia de energía entre el LUMO y el HOMO (band gap, Eg) y el potencial de ionización (PI) fue calculada a partir de las geometrías optimizadas en DFT para el estado neutro, anión y catión. Los PI y la Eg de los copolímeros fueron obtenidos mediante la extrapolación de los valores del oligómero a (1/N) y de una cadena de longitud infinita (1/N=0), obteniéndose una correlación lineal (R=0,99), la cual se mantiene a lo largo de todos los modelos de ajuste de cada copolímero analizado en el estudio.

Abstract There has been great scientific and technological interest in the use of mono-substituents of furan and thiophene as conducting polymers due to their multiple applications such as OLED, optical amplifiers and nanotechnology, among others. For this, the purpose of this work was to study the theoretical aspects that affect the electroconductive properties of this type of molecules. The structural and electronic properties that influence the conductivity of mono substituted-furan-thiophene copolymers were determined theoretically. The effect of using carboxyl, methyl, hydroxyl, cyano, and fluoride groups as substituents on the carbon C3 and C10 of each heterocycle was observed. The energy difference between the LUMO and the HOMO (band gap, Eg) and the ionization potential (IP) were calculated from the geometries optimized in DFT for the neutral, anion and cation state. The PI and Eg of the copolymers were obtained by extrapolating the values of the oligomer a (1/N) and a chain of infinite length (1/N=0) for which a linear correlation was obtained (R=0.99). This correlation is maintained throughout all the adjustment models of each copolymer analyzed in the study.

Resumo Existe muito interesse os termos científicos e tecnológicos em utilizar substituintes mono-substituídos furano e tiofeno como polímeros condutores devido às suas múltiplas aplicações, tais como OLED, amplificadores ópticos e nanotecnologia, entre outros. O objetivo deste trabalho foi estudar os aspectos teóricos que afetam as propriedades eletrocondutoras deste tipo de moléculas. Neste contribuição os aspectos estruturais e electrónicas que influenciam a condutividade de copolímeros furano-tiofeno substituos mono teoricamente determinada observando o efeito do uso de grupos carboxilo, metilo, hidroxilo, ciano e fluoretos como substituintes em C3 e C10 de carbono de cada heterociclo. A diferença de energia entre o LUMO e o HOMO (intervalo de banda, Eg) e o potencial de ionização (IP) foram calculadas a partir das geometrias optimizadas de DFT para o estado neutro, anião e catião. O PI e o Eg dos copolímeros foram obtidos por extrapolação dos valores do oligómero (1/N) e extrapolando para uma cadeia de comprimento infinito (1/ N=0) para os quais uma correlação linear foi obtida (R=0,99), que é mantido ao longo de todos os modelos de ajuste de cada copolímero analisados no estudo.

La pliometría y su incidencia en la velocidad y velocidad-fuerza en jugadoras de fútbol / Plyometrics and its impact on the speed and speed-strength of female soccer players

Introducción: El método pliométrico es un modelo de estiramiento-acortamiento orientado a la mejora de la velocidad y la potencia en deportistas. Si bien existen investigaciones que valorar los efectos de la pliometría en futbolistas masculinos de diferentes rangos etarios, existe la necesidad de valorar los alcances y limitaciones de la aplicación pliométrica en el sexo femenino a corto plazo. Objetivo: Determinar la incidencia del método pliométrico a corto plazo en la velocidad y velocidad-fuerza en mujeres futbolistas de la categoría senior. Métodos: Se estudió la población de mujeres futbolistas de categoría senior (18 sujetos), implementando un programa pliométrico de 3 microciclos de adaptación inicial y 5 microciclos de intervención pliométrica, se valoró los efectos en la velocidad y la velocidad-fuerza a través de dos pruebas de valoración del rendimiento deportivo, antes y después de implementada la propuesta. Resultados: Se evidenciaron mejorías significativas en el postest como parte del Jump test (p=0,000), y significativas en el postest de las tres fases de la prueba de 40m (p= 0,000). Conclusiones: se demuestran mejoras significativas en las capacidades de velocidad y velocidad-fuerza en mujeres futbolistas de la categoría senior, indicando para el presente estudio que el entrenamiento pliométrico es efectivo en el sexo femenino para potenciar los indicadores del rendimiento deportivo antes mencionados(AU)

Introduction: The plyometric method is a stretch-shortening model aimed at improving the speed and strength of sportspeople. Studies have been conducted assessing the effects of plyometrics on male soccer players of various age ranges. It is therefore necessary to evaluate the short-term scope and limitations of the plyometric method as applied to female players. Objective: Determine the short-term impact of the plyometric method on the speed and speed-strength of female soccer players from the senior category. Methods: A study was conducted of a population of female soccer players from the senior category (18 subjects), implementing a plyometric program composed of three microcycles for initial adaptation and a five-microcycle plyometric intervention. Evaluation was performed of the effects on speed and speed-strength applying two sport performance tests, one before and one after implementation of the proposal. Results: Improvement was significant in the post-test as part of the jump test (p= 0.000), as well as in the post-test for the three phases of the 40 m test (p= 0.000). Conclusions: Significant speed and speed-strength improvement is observed in female soccer players from the senior category, showing that plyometric training is effective to strengthen the aforementioned sport performance indicators in the female sex(AU)

Assessing Parasite Load in Chagas Disease Patients by Quantitative Multiplex Real-Time PCR.

The development of accurate diagnostic tools and surrogate markers of parasitological response to treatment are priorities in Chagas disease (CD) research. For years, the detection of Trypanosoma cruzi DNA by PCR has proved to be useful in some clinical scenarios like acute CD, including cases of congenital transmission, CD reactivation in immunosuppressed patients, and posttreatment follow-up. In that sense, the implementation of quantitative real-time PCR (qPCR) assays was an important step in the development of more reliable tools for CD molecular diagnostics and treatment follow-up. In the last decade, two multicenter PCR studies allowed the harmonization and validation of standard operating procedures for PCR-based detection and quantification of T. cruzi DNA in blood samples. Herein we describe the two most used protocols to quantify parasitic load in human blood samples by multiplex qPCR assays and discuss some aspects to consider during planning and executing these procedures.

Genotyping of Trypanosoma cruzi from Clinical Samples by Multilocus Conventional PCR.

By the most recent nomenclature, Trypanosoma cruzi isolates are classified into six discrete typing units (DTUs)-T. cruzi I to T. cruzi VI and TcBat. One of the major challenges in the Chagas disease study is to find an association between DTUs and clinical manifestations of the disease or response to treatment. Herein, a protocol based on the amplification of T. cruzi SL-IRac, SL-IR I and II, 24Sα rDNA, and A10 targets by multilocus conventional PCRs is described. Following this methodology, it is possible to perform the genotyping directly from the blood and other clinical samples, without the need to isolate the parasite prior to the DNA extraction, even in a lower parasite concentration. Furthermore, this methodology increases the probability to detect mixed infections, avoiding a possible selection of strains during the parasite isolation.

Usefulness of Serial Blood Sampling and PCR Replicates for Treatment Monitoring of Patients with Chronic Chagas Disease.

This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real-time quantitative PCR (qPCR) for baseline detection and quantification of parasitic loads and posttreatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely, DNDi-CH-E1224-001 (ClinicalTrials.gov registration no. NCT01489228) and the MSF-DNDi PCR Sampling Optimization Study (NCT01678599). Patients from Cochabamba (n = 294), Tarija (n = 257), and Aiquile (n = 220) were enrolled. Three serial blood samples were collected at each time point, and qPCR triplicates were tested for each sample. The first two samples were collected during the same day and the third one 7 days later. A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pretreatment sample positivity from 54.8% to 76.2%, 59.5% to 77.8%, and 73.5% to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively. This strategy increased the detection of treatment failure from 72.9% to 91.7%, 77.8% to 88.9%, and 42.9% to 69.1% for E1224 low-, short-, and high-dosage regimens, respectively, and from 4.6% to 15.9% and 9.5% to 32.1% for the benznidazole arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The addition of the third blood sample and third qPCR replicate in patients with nondetectable PCR results in the first two samples gave a small, non-statistically significant improvement in qPCR positivity. No change in clinical sensitivity was seen with a blood volume increase from 5 to 10 ml. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasionally nondetectable results. In conclusion, a serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials, which require an initial positive qPCR result for patient admission.

Tyrphostin AG17 inhibits adipocyte differentiation in vivo and in vitro.

BACKGROUND: Excessive subcutaneous adiposity in obesity is associated to positive white adipocyte tissue (WAT) differentiation (adipogenesis) and WAT expandability. Here, we hypothesized that supplementation with the insulin inhibitor and mitochondrial uncoupler, Tyrphostin (T-AG17), in vitro and in vivo inhibits adipogenesis and adipocyte hypertrophy. METHODS: We used a 3T3-L1 proadipocyte cell line to identify the potential effect of T-AG17 on adipocyte differentiation and fat accumulation in vitro. We evaluated the safety of T-AG17 and its effects on physiological and molecular metabolic parameters including hormonal profile, glucose levels, adipogenesis and adipocyte hypertrophy in a diet-induced obesity model using C57BL/6 mice. RESULTS: We found that T-AG17 is effective in preventing adipogenesis and lipid synthesis in the 3T3-L1 cell line, as evidenced by a significant decrease in oil red staining (p < 0.05). In obese C57BL/6 mice, oral administration of T-AG17 (0.175 mg/kg for 2 weeks) lead to decreased fat accumulation and WAT hypertrophy. Further, T-AG17 induced adipocyte apoptosis by activating caspase-3. In the hepatocytes of obese mice, T-AG17 promoted an increase in the size of lipid inclusions, which was accompanied by glycogen accumulation. T-AG17 did not alter serum biochemistry, including glucose, insulin, leptin, free fatty acids, creatinine, and aspartate aminotransferase. CONCLUSION: T-AG17 promotes adipocyte apoptosis in vivo and is an effective modulator of adipocyte differentiation and WAT hypertrophy in vitro and in vivo. Therefore, T-AG17 may be useful as a pharmacological obesity treatment.

Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection by Trypanosoma cruzi.

PROBLEM: The innate immune response of the placenta may participate in the congenital transmission of Chagas disease through releasing reactive oxygen and nitrogen intermediates. METHOD OF STUDY: Placental explants were cultured with 1 × 106 and 1 × 105 trypomastigotes of Tulahuen and Lucky strains and controls without parasites, and with the addition of nitric oxide synthase inhibitor Nω-Nitro-l-arginine methyl ester (l-NAME) and N-acetyl cysteine (NAC) as the reactive oxygen species (ROS) scavenger. Detachment of the syncytiotrophoblast (STB) was examined by histological analysis, and the nitric oxide synthase, endothelial (eNOS), and nitrotyrosine expressions were analyzed by immunohistochemistry, as well as the human chorionic gonadotrophin (hCG) levels in the culture supernatant through ELISA assays. Parasite load with qPCR using Taqman primers was quantified. RESULTS: The higher number of T. cruzi (106 ) increased placental infection, eNOS expression, nitrosative stress, and STB detachment, with the placental barrier being injured by oxidative stress. CONCLUSION: The higher number of parasites caused deleterious consequences to the placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage caused by trypomastigotes in placental villi but not that of the infection. Moreover, trophoblast eNOS played a key role in placental infection with the highest inoculum of Lucky, demonstrating the importance of the enzyme and nitrosative-oxidative stress in Chagas congenital transmission.