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Recent strides in understanding the molecular underpinnings of head and neck cancers have sparked considerable interest in identifying precise biomarkers that can enhance prognostication and enable personalized treatment strategies. Immunotherapy has particularly revolutionized the therapeutic landscape for head and neck squamous cell carcinoma, offering new avenues for treatment. This review comprehensively examines the application and limitations of the established and emerging/novel biomarkers for head and neck squamous cell carcinoma. Established biomarkers, including well-characterized genetic mutations, protein expressions, and clinical factors, have been extensively studied and validated in clinical practice. Novel biomarkers identified through molecular analyses, including novel genetic alterations, immune-related markers, and molecular signatures, are currently being investigated and validated in preclinical and clinical settings. Biomarkers hold the potential to deepen our understanding of head and neck squamous cell carcinoma biology and guide therapeutic strategies. The evolving paradigm of predictive biomarkers facilitates the study of individual responses to specific treatments, including targeted therapy and immunotherapy.

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P

Este artículo revisa las iniciativas sobre la gestión de propiedad intelectual de las vacunas y otros productos de salud relacionados con la COVID-19. Se adentra en el análisis de la discusión de la exención de los derechos en el marco de los ADPIC de la OMC. Los argumentos a favor de la renuncia se centran en la necesidad de facilitar el acceso a medicamentos y tecnologías de salud esenciales, mientras que los argumentos en contra se basan en preocupaciones sobre la eficacia, legalidad y posibles efectos negativos en la innovación y el crecimiento del sector de las tecnologías de salud. Se concluye que la decisión no tuvo un impacto significativo en la fabricación o acceso a las vacunas, generando interrogantes sobre si la decisión se tomó demasiado tarde durante la pandemia y si su terminología y redacción podrían obstaculizar su aplicación efectiva. La vigencia, pertinencia e impacto de la decisión dependerán de la continua necesidad de garantizar un acceso global asequible a las vacunas.

Sports-related muscle injuries account for 10–55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences (p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies.

Resumen: Introducción y objetivos: La presencia de insuficiencia mitral isquémica comporta una mayor mortalidad. Entre las diferentes opciones de tratamiento se diseñó el anillo IMR para corregir las alteraciones específicas de la insuficiencia mitral isquémica. Describimos nuestra experiencia con el anillo IMR en la insuficiencia mitral isquémica. Métodos: Estudio retrospectivo de todos los pacientes operados entre 2006 y 2022 con corrección de insuficiencia mitral isquémica mediante anuloplastia simple con anillo IMR. Se ha revisado registros clínicos y realizado un seguimiento telefónico. Resultados: Se incluyeron 185 pacientes. El 81% presentaba disfunción ventricular y el 62,2% lesión de 3 vasos. El 17,9% tenía insuficiencia mitral moderada y el 82,1% severa. El 51,1% fueron operados de forma urgente, con un infarto reciente el 64,4% y en situación de insuficiencia cardíaca el 43,7%. Al 96,2% se les realizó también revascularización miocárdica.El 69,8% no presentó insuficiencia mitral residual y el 25,1% insuficiencia ligera. La libertad de reintervención mitral es del 98% a los 15 años de la cirugía.La mortalidad hospitalaria fue del 2,7%. La supervivencia es de 92,5% al año, 72% a los 5 años, 54% a los 10 años y 26% a los 15 años tras la cirugía.De los pacientes vivos contactados (63%), el 91,8% se mantiene en clase funcional I-II. Conclusiones: El anillo IMR es un anillo específico para la corrección de la insuficiencia mitral isquémica, que permite repararla de forma efectiva con una técnica sencilla, sin aumentar las complicaciones iniciales, y consiguiendo una mejor supervivencia a largo plazo. Abstract: Introduction and objectives: The presence of ischemic mitral regurgitation leads to higher mortality. Among the different treatment options, the IMR ring was designed to correct the specific alterations of ischemic mitral regurgitation. We report our experience with IMR ring in ischemic mitral regurgitation. Methods: Retrospective study of all patients operated between 2006 and 2022 with ischemic mitral regurgitation correction by simple annuloplasty with IMR ring. Clinical records have been reviewed and telephone follow-up has been carried out. Results: One hundred and eighty-five patients were included. 81% had ventricular dysfunction and 62.2% three vessel disease. 17.9% had moderate mitral regurgitation and 82.1% severe mitral regurgitation. 51.1% of the patients underwent urgent surgery, 64.4% had a recent myocardial infarction and 43.7% had heart failure. 96.2% also underwent myocardial revascularization. Hospital mortality was 2.7%. Survival is 92.5% at one year, 72% at 5 years, 54% at 10 years, and 26% at 15 years after surgery. 69.8% did not present residual mitral insufficiency and 25.1% mild insufficiency. Freedom from mitral reoperation is 98% at 15 years after surgery. Of the living contacted patients (63%), 91.8% remain in functional class I–II. Conclusions: The IMR ring is a specific ring for IMi correction, which allows IMi to be repaired effectively with a simple technique, without increasing initial complications, and achieving better long-term survival.

As the first responders, neutrophils lead the innate immune response to infectious pathogens and inflammation inducing agents. The well-established pathogen neutralizing strategies employed by neutrophils are phagocytosis, the action of microbicide granules, the production of ROS, and the secretion of neutrophil extracellular traps (NETs). Only recently, the ability of neutrophils to sense and respond to pathogen-associated molecular patterns is being appreciated. This review brings together the current information about the intracellular recognition of DNA by neutrophils and proposes models of signal amplification in immune response. Finally, the clinical relevance of DNA sensing by neutrophils in infectious and non-infectious diseases including malignancy are also discussed.

The efficacy of cancer therapies is limited to a great extent by immunosuppressive mechanisms within the tumor microenvironment (TME). Numerous immune escape mechanisms have been identified. These include not only processes associated with tumor, immune or stromal cells, but also humoral, metabolic, genetic and epigenetic factors within the TME. The identification of immune escape mechanisms has enabled the development of small molecules, nanomedicines, immune checkpoint inhibitors, adoptive cell and epigenetic therapies that can reprogram the TME and shift the host immune response towards promoting an antitumor effect. These approaches have translated into series of breakthroughs in cancer therapies, some of which have already been implemented in clinical practice. In the present article the authors provide an overview of some of the most important mechanisms of immunosuppression within the TME and the implications for targeted therapies against different cancers.

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase–Pluronic mixture exhibited a significant increase in the cross-sectional area (p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization (p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.

Background One of the most severe complications in laparoscopic cholecystectomy (LC) is intraoperative bile duct injury (BDI). Despite its low incidence, the medical implications for the patient can be serious. Besides, BDI can also generate significant legal issues in healthcare. Different techniques have been described to reduce the incidence of this complication, and near-infrared fluorescence cholangiography with indocyanine green (NIRFC-ICG) is one of the latest additions. In spite of the great interest aroused by this procedure, there are currently great disparities in the usage or administration protocols of ICG.Methods and analysis This is a randomised, multicentre, per-protocol analysis, open clinical trial with four arms. The estimated duration of the trial is 12 months. The aim of the study is to analyse whether there are differences between the dose and administration ICG intervals to obtain good-quality NIRFC during LC. The primary outcome is the degree of identification of critical biliary structures during LC. In addition, different factors will be analysed that may have an influence on the results of this technique.Ethics and dissemination The trial will be conducted according to the recommendations for Clinical Trials in the Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects and the recommendations of the Spanish Agency of Medicines and Medical Devices (AEMPs) for clinical trials. This trial was approved by the local institutional Ethics Committee and the AEMPs. The results of the study will be presented to the scientific community through publications, conferences or other means.EudraCT number 2022-000904-36.Protocol version V.1.4, 2 June 2022Trial registration number NCT05419947.

Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of hyperphosphorylated tau in neurons and glia. Primary tauopathies are not uncommon in humans but exceptional in other species. We evaluate the clinical, neuropathological, and genetic alterations related to tau pathology in 16 cats aged from 1 to 21 years with different clinical backgrounds. Interestingly, a 10-year-old female cat presented a six-year progressive history of mental status and gait abnormalities. The imaging study revealed generalized cortical atrophy. Due to the poor prognosis, the cat was euthanatized at the age of ten. Neuropathological lesions were characterized by massive neuronal loss with marked spongiosis and associated moderate reactive gliosis in the parietal cortex, being less severe in other areas of the cerebral cortex, and the loss of Purkinje cells of the cerebellum. Immunohistochemical methods revealed a 4R-tauopathy with granular pre-tangles in neurons and coiled bodies in oligodendrocytes. Deposits were recognized with several phospho-site antibodies (4Rtau, tau5, AT8, PFH, tau-P Thr181, tau-P-Ser 262, tau-P Ser 422) and associated with increased granular expression of active tau kinases (p38-P Thr180/Tyr182 and SAPK/JNK-P Thr138/Thr185). The genetic study revealed well-preserved coding regions of MAPT. No similar alterations related to tau pathology were found in the other 15 cats processed in parallel. To our knowledge, this is the first case reporting a primary 4R-tauopathy with severe cerebral and Purkinje cell degeneration in an adult cat with neurological signs starting at a young age.

Introduction: Advanced non-small cell lung cancer (aNSCLC) is an incurable disease. The effort to develop treatments with more effective systemic agents continues. This has led to the FDA approval of one antibody–drug conjugate (ADC) and eight immune checkpoint inhibitors (ICIs) for patients with aNSCLC. Areas covered: Due to the demonstrated efficacy of ADCs and ICIs in aNSCLC, treatment combining both agents merits attention. This article, therefore, explores the use of ADCs and ICIs in patients with NSCLC, assesses the scientific rationale for combination treatment, and provides an overview of ongoing trials. It also presents some early efficacy and safety results of such combination use. Expert opinion: It is not clear whether ADC-immunotherapy has a significant impact on those with a targetable oncogenic driver alteration since targeted therapies are effective. However, in aNSCLC without a targetable oncogenic driver alteration, the combination of ADCs and ICIs has potential and remains an area of active clinical research.

Objectives To explore variables associated with adverse maternal/fetal/neonatal outcomes among pregnant/postpartum patients admitted to ICU for hypertensive disorders of pregnancy (HDP). Methods Multicenter, prospective, national cohort study. Results Variables independently associated with maternal/fetal/neonatal mortality among 172 patients were as follows: Acute Physiology and Chronic Health Evaluation-II (APACHE-II)(OR1.20[1.06–1.35]), gestational age (OR0.698[0.59–0.82]) and aspartate aminotransferase (AST)(OR1.004[1.001–1.006]). Positive likelihood ratio for headache, epigastric pain, and visual disturbances to predict composite adverse outcomes were 1.23(1.16–1.30), 0.76(0.59–1.02), and 1.1(0.98–1.2), respectively. Conclusions Maternal/fetal mortality due to HDP was independently associated with severity of illness on admission, gestational age, and elevated AST. Accuracy of clinical symptoms to predict composite adverse outcomes was low.

Resumen: La ecocardiografía transesofágica intraoperatoria se ha convertido en un aliado indispensable para el cirujano cardiaco, especialmente en la cirugía de reparación mitral. La evaluación de la insuficiencia mitral residual debe realizarse en todos los casos de reparación mitral, una vez optimizadas las condiciones de presión y contractilidad ventricular tras la salida de circulación extracorpórea, y debe valorar la presencia y severidad de la insuficiencia mitral residual, el mecanismo y la localización de la misma y las posibles complicaciones asociadas. Este artículo trata de revisar las peculiaridades de esta técnica, los puntos claves de la valoración del resultado quirúrgico, así como su importancia en la toma de decisiones. Abstract: Intraoperative transesophageal echocardiography has become an indispensable ally for the cardiac surgeon, especially in mitral repair surgery. The evaluation of residual mitral regurgitation should be carried out in all cases of mitral repair, once the conditions of pressure and ventricular contractility have been optimized after the cardiopulmonary bypass, and should assess the presence and severity of residual mitral regurgitation, the mechanism and its location and possible associated complications. This article tries to review the peculiarities of this technique, the key points in the assessment of the surgical result, as well as its importance in decision-making.

Resumen: Introducción: La reparación valvular en la insuficiencia mitral precisa de formación específica y experiencia suficientes para alcanzar la excelencia en los resultados. A nivel nacional la tasa de reparación valvular mitral respecto al total de intervenciones mitrales se sitúa en el 30%.El objetivo del estudio es presentar los resultados de reparación mitral en un centro de referencia nacional de reparación valvular. Método: Estudio retrospectivo de todos los pacientes sometidos a reparación mitral aislada o combinada del servicio de cirugía cardíaca de nuestro centro, desde diciembre de 2002 hasta diciembre de 2021. Análisis descriptivo de variables preoperatorias, intraoperatorias y resultados postoperatorios. Resultados: Un total de 934 pacientes de reparación mitral fueron incluidos, con una edad media de 68 años y un EuroSCORE Log y II medios del 8,15 y 5,22%, respectivamente. La tasa de reparación mitral fue del 63,5%. El 35,7% de pacientes se encontraban en insuficiencia cardíaca. El 35% presentaba disfunción ventricular izquierda ≤ 40%. Las principales etiologías de las insuficiencias mitrales fueron degenerativas (42,5%), seguidas de isquémicas (25,3%). El 64,9% fueron reparaciones complejas.La mortalidad fue del 2,1%, con predominio de las endocarditis e isquémicas, con una tasa de complicaciones mayores del 6,3%. La estancia mediana fue de 9 días.El 98% de pacientes presentaron insuficiencia mitral residual grado

Resumen: Introducción: La cardioplejia Custodiol® ofrece protección miocárdica durante tres horas mediante dosis única permitiendo realizar procedimientos complejos sin interrupción. Existe discusión respecto a la conveniencia de la protección miocárdica ofrecida mediante dosis única. Objetivo: Comparar resultados de morbimortalidad perioperatorios de cardioplejia cristaloide usada en nuestro centro (St. Thomas no. 2 [ST2]) respecto a Custodiol en cirugías complejas. Material y método: Estudio retrospectivo comparativo en pacientes intervenidos desde mayo 2016 a diciembre 2019 de cirugía cardíaca con tiempos de pinzamiento mayor de 80 minutos, clasificados según el tipo de cardioplejia: grupo ST2 vs. grupo Custodiol. Resultados: Se incluyeron 712 pacientes: 548 en grupo ST2 y 164 en grupo Custodiol. Respecto a las variables preoperatorias, en el grupo Custodiol hubo más mujeres, más reintervenciones, mayor número de casos emergentes y un EuroSCORE Logístico y ii más elevados (4,90% vs. 7,19%, p = 0,000).Además, el grupo Custodiol presentó mayores tiempos de circulación extracorpórea (CEC) (127 vs. 149 minutos, p = 0,000) y de pinzamiento (106 vs. 124 minutos, p = 0,0001) y un mayor porcentaje de pacientes requirió desfibrilación tras el despinzamiento (16,2% vs. 34,6%, p = 0,000).La mortalidad operatoria fue similar (3,8% vs. 6,1%, p = 0,152). La estancia hospitalaria fue dos días mayor en el grupo Custodiol.En el análisis multivariante, el tipo de cardioplejia no resultó factor de riesgo independiente para morbilidad postoperatoria ni mortalidad. Conclusiones: Nuestro centro propone Custodiol® en casos complejos con tiempos de pinzamiento largos como alternativa comparable y segura a la cardioplejia cristaloide convencional, ya que ofrece una cómoda protección miocárdica con la misma incidencia de complicaciones postoperatorias. Abstract: Introduction: Custodiol® cold crystalloid cardioplegia offers myocardial protection for up to three hours with one single dose, allowing to perform complex procedures without interruption. There is concern about the adequacy of single dose cardioplegia in terms of myocardial protection. Objective: To compare results of perioperative morbidity and mortality of conventional crystalloid cardioplegia used in our hospital (St.Thomas 2 [ST2]) versus Custodiol in complex cardiac surgery. Methods: A retrospective comparative study was conducted between patients who underwent cardiac surgery with aortic cross-clamping times over 80 minutes, from May 2016 until December 2019. They were divided into two groups of cardioplegia: ST2 group versus Custodiol group. Results: The study included 712 patients, of whom 548 were in ST2 group and 164 in Custodiol group. Preoperative variables showed a greater number of women, re-interventions, and emergent cases, with the highest EuroSCORE ii (4.90% vs. 7.19%, p = 0.000) in the Custodiol group.The Custodiol group also had longer cardiopulmonary bypass times (127 vs. 149 minutes, p = 0.000) and aortic cross-clamping times (106 vs. 124 minutes, p = 0.0001), and a greater number of ventricular arrhythmias that needed defibrillation (16.2% vs. 34.6%, p = 0.000).Surgical mortality did not show any differences (3.8% vs. 6.1%, p = 0.152). Hospital stay was two days longer in the Custodiol group.In multivariate analysis, type of cardioplegia did not result in an independent risk factor for post-operative morbidity and mortality. Conclusions: This hospital centre proposes the use of Custodiol in complex cardiac surgery with prolonged aortic cross-clamping times as a safe alternative to conventional crystalloid cardioplegia, as it offers good myocardial protection for surgeons, with same incidence of post-operative complications.

As a result of the unprecedented challenges imposed by the COVID-19 pandemic on enrollment to cancer clinical trials, there has been an urgency to identify and incorporate new solutions to mitigate these difficulties. The concept of decentralized or hybrid clinical trials has rapidly gained currency, given that it aims to reduce patient burden, increase patient enrollment and retention, and preserve quality of life, while also increasing the efficiency of trial logistics. Therefore, the clinical trial environment is moving toward remote collection and assessment of data, transitioning from the classic site-centric model to one that is more patient-centric.

Alzheimer’s disease (AD) is the most common type of dementia and neurodegeneration. The actual cause of AD progression is still unknown and no curative treatment is available. Recently, findings in human samples and animal models pointed to the endocannabinoid system (ECS) as a promising therapeutic approach against AD. However, the specific mechanisms by which cannabinoid drugs induce potential beneficial effects are still undefined. For this reason, it is required a full characterization of the ECS at different time points of AD progression considering important factors such as sex or the analysis of different brain regions to improve future cannabinoid-dependent therapies in AD. Thus, the main aim of the present study is to expand our knowledge of the status of the ECS in a presymptomatic period (3 months of age) using the AD mouse model APP/PS1 mice. First, we evaluated different behavioral domains including anxiety, cognitive functions, and social interactions in male and female APP/PS1 mice at 4 months of age. Although a mild working memory impairment was observed in male APP/PS1 mice, in most of the behaviors assessed we found no differences between genotypes. At 3 months of age, we performed a characterization of the ECS in different brain regions of the APP/PS1 mice considering the sex variable. We assessed the expression of the ECS components by quantitative Real-Time Polymerase Chain Reaction in the hippocampus, prefrontal cortex, hypothalamus, olfactory bulb, and cerebellum. Interestingly, gene expression levels of the type-1 and type-2 cannabinoid receptors and the anabolic and catabolic enzymes, differed depending on the brain region and the sex analyzed. For example, CB1R expression levels decreased in both hippocampus and prefrontal cortex of male APP/PS1 mice but increased in female mice. In contrast, CB2R expression was decreased in females, whereas males tended to have higher levels. Overall, our data indicated that the ECS is already altered in APP/PS1 mice at the presymptomatic stage, suggesting that it could be an early event contributing to the pathophysiology of AD or being a potential predictive biomarker.

Resumen: Introducción: En la actualidad no existe ninguna comparación de la capacidad predictiva de las diferentes escalas específicas de riesgo quirúrgico en endocarditis infecciosa. Objetivo: Comparar la utilidad de las diferentes escalas específicas publicadas. Material y métodos: Estudio observacional, retrospectivo y unicéntrico. Se incluyeron 180 pacientes, en los que se calcularon 10 escalas. Se calculó la mortalidad estimada por cada escala y se comparó con la mortalidad observada, con su estimación a través del intervalo de confianza del 95%. Se valoró la discriminación, por el área bajo la curva ROC (AUC), y la calibración con el test de Homer-Lemeshow (HLt). Resultados: La mortalidad observada fue del 26,82% (IC 95%: 20,74-33,57%). Las escalas STS-EI, De Feo y AEPEI infraestimaron la mortalidad; las escalas de Costa y Endoscore la sobreestimaron. La escala de Costa presentó una baja discriminación y AEPEI demostró una calibración subóptima.En nuestra serie, las escalas que demostraron una estimación precisa fueron: 1) PALSUSE: mortalidad predicha 15-30%, AUC = 0,68 (IC 95%: 0,58-0,76) y HLt p = 0,46; 2) RISK-E score: estima mortalidad 0-30%, AUC = 0,76 (IC 95%: 0,69-0,82) y HLt p = 0,35; 3) SpecificEuroSCORES I y II: mortalidad estimada 30-40%, AUC = 0,76 (IC 95%: 0,69-0,82) y HLt p = 0,42 en I y AUC = 0,74 (IC 95%: 0,66-0,79) con HLt = 0,75 en II; 4) APORTEI: predice mortalidad de 20-40%, AUC = 0,75 (IC 95%: 0,68-0,82) y HLt p = 0,73. Conclusiones: De las 10 escalas analizadas, PALSUSE, RISK-E, SpecificEuroSCORE y APORTEI demostraron una predicción de mortalidad precisa y una adecuada capacidad predictiva en el postoperatorio inmediato de cirugía cardiaca por endocarditis infecciosa. Abstract: Introduction: A direct comparison among specific endocarditis risk scores has not yet been conducted. Objective: Compare the previously published endocarditis specific scores and analyze their prognostic accuracy. Material and methods: We performed an observational single-center and retrospective study. 180 patients were included, and 10 specific risk scores were calculated. Estimated mortality was calculated for each score and it was compared with the observed mortality, with its 95% confidence interval estimation. Discrimination was assessed by area under the ROC curve (AUC) and calibration was assessed by Homer-Lemeshow test (HLt). Results: Observed surgical mortality was 26.82% (95% CI: 20.74-33.57). STS-EI, De Feo and AEPEI scores underestimated mortality, whereas Costa score and Endoscore overestimated mortality. Costa score demonstrated a low discrimination (AUC = 0.65, 95% CI 0.57-0.72) and AEPEI showed a suboptimal calibration (P = .025). Results: showed an accurate estimated mortality in: 1) PALSUSE showed predicted mortality to be between 15-30%, AUC = 0.68 (95% CI: 0.58-0.76) and HLt P = .46; 2) RISK-E score estimated a mortality of 0-30%, AUC = 0.76 (95% CI: 0.69-0.82) and HLt P = .35; 3) SpecificEuroSCORES I y II with an estimated mortality of 30-40%, AUC = 0,76 (95% CI: 0,69-0,82) y HLt P = .42 for SpecificEuroSCORES I and AUC = 0.74 (95% CI: 0,66-0,79) con HLt = 0,75 in SpecificEuroSCORES II; 4) APORTEI showed predicted mortality to be between 20 and 40%, with AUC = 0.75 (95% CI: 0.68-0.82) and HLt P = .73. Conclusion: Among the 10 assessed endocarditis specific scores scores, PALSUSE, RISK-E, SpecificEuroSCORE and APORTEI demonstrated an optimal mortality risk estimation and an adequate predictive capacity for postoperative mortality in the postoperative period after cardiac surgery for infective endocarditis.

Objetivo: El objetivo de este estudio fue evaluar la eficacia de la Terapia Asistida con Perros (TAP) en niños y adolescentes con Trastorno del Espectro Alcohólico Fetal (TEAF). Método: Realizamos un ensayo piloto aleatorizado y controlado, cegado por el evaluador, en una cohorte de 33 niños y adolescentes con TEAF. Los participantes fueron asignados aleatoriamente al grupo TAP (n=17) o al tratamiento habitual (n=16). Resultados: De los 39 participantes iniciales inscritos, 33 completaron el tratamiento. Un análisis de modelo de efectos mixtos reveló que los participantes que fueron asignados al grupo TAP experimentaron mejoras significativas en habilidades sociales (SSIS-P Habilidades sociales: p = 0.02; d = 0.8), reducciones en los síntomas de externalización (CBCL Externalización p = 0.03; d = 0.56) y puntuaciones más bajas en la severidad del TEAF (CGI-S Clínico: p = 0.001; d = 0.5). Conclusiones: La TAP parece ser un tratamiento complementario prometedor para niños y adolescentes con TEAF.

The rationale of this study was to evaluate the efficacy of Dog-assisted Therapy (DAT) in children and adolescents with Fetal Alcohol Spectrum Disorder (FASD). We conducted a randomized controlled trial in a cohort of 71 children and adolescents with FASD. Participants were randomly assigned either to DAT group (n = 38) or Relaxation Group (control group) (n = 33). Results revealed that participants who were assigned to the DAT group experienced significantly reduced externalizing symptoms (CBCL Externalizing Inattention: t (69) = 2.81, p = 0.007; d = 0.7); CBCL Opposition: t (69) = 2.54, p = 0.013; d = 0.6), reduced internalizing symptoms (CBCL Social problems: t (69) = 3.21, p = 0.002; d = 0.8) as well as improvements on social skills (SSIS-P Problem behavior: t (68) = 2.55, p = 0.013; d = 0.6), and quality of life (KidScreen Autonomy and Parents: t (51) = - 2.03, p = 0.047; d = 0.5) compared to the relaxation control group. The relaxation control group obtained significant differences between the pre- and post-treatment evaluation, diminishing withdraw symptoms (t (32) = 3.03, p = 0.005; d = 0.2). Results suggest that DAT and relaxation may be promising adjunctive treatments for children and adolescents with FASD.

Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography [with Controlled Attenuation Parameter (CAP) measurements] was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p

Background. Changes in BUN have been proposed as a risk factor for complications in acute pancreatitis (AP). Our study aimed to compare changes in BUN versus the Bedside Index for Severity in Acute Pancreatitis (BISAP) score and the Acute Physiology and Chronic Health Evaluation-II score (APACHE-II), as well as other laboratory tests such as haematocrit and its variations over 24 h and C-reactive protein, in order to determine the most accurate test for predicting mortality and severity outcomes in AP. Methods. Clinical data of 410 AP patients, prospectively enrolled for study at our institution, were analyzed. We define AP according to Atlanta classification (AC) 2012. The laboratory test’s predictive accuracy was measured using area-under-the-curve receiver-operating characteristics (AUC) analysis and sensitivity and specificity tests. Results. Rise in BUN was the only score related to mortality on the multivariate analysis (p=0.000, OR: 12.7; CI 95%: 4.2−16.6). On the comparative analysis of AUC, the rise in BUN was an accurate test in predicting mortality (AUC: 0.842) and persisting multiorgan failure (AUC: 0.828), similar to the BISAP score (AUC: 0.836 and 0.850) and APACHE-II (AUC: 0.756 and 0.741). The BISAP score outperformed both APACHE-II and rise in BUN at 24 hours in predicting severe AP (AUC: 0.873 vs. 0.761 and 0.756, respectively). Conclusion. Rise in BUN at 24 hours is a quick and reliable test in predicting mortality and persisting multiorgan failure in AP patients.

ObjectiveThe rationale of this study was to evaluate the efficacy of dog-assisted therapy (DAT) combined with pharmacological treatment in children and adolescents with fetal alcohol spectrum disorder (FASD).MethodWe conducted a randomized, rater-blinded, controlled pilot trial in a cohort of 33 children and adolescents with FASD. Participants were randomly assigned either to DAT group (n = 17) or Treatment as Usual (TAU control group) (n = 16).ResultsOf the initial 39 participants enrolled, 33 completed treatment. A mixed-effects model analysis revealed that participants who were assigned to the DAT group experienced significantly improvements on social skills (SSIS-P social skills: p = 0.02, d = 0.8), reductions on externalizing symptoms (CBCL externalizing: p = 0.03; d = 0.56), and lower scores on FASD severity (CGI-S clinician: p = 0.001, d = 0.5).ConclusionDAT is a promising adjunctive treatment for children and adolescents with FASD.Clinical Trial RegistrationDog-assisted therapy for children and adolescents with fetal alcohol spectrum disorders: a randomized controlled pilot study; http://clinicaltrials.gov/, identifier NCT04038164.

Enterococcus faecalis infective endocarditis (EFIE) is a severe disease of increasing incidence. The objective was to analyze whether the outcome of patients with native valve EFIE (NVEFIE) treated with a short course of ampicillin plus ceftriaxone (4wAC) was similar to patients treated according to international guidelines (6wAC). Between January 2008 and June 2018, 1,978 consecutive patients with definite native valve IE were prospectively included in a national registry. Outcomes of patients with NVEFIE treated with 4wAC were compared to those of patients who received 6wAC. Three hundred and twenty-two patients (16.3%) had NVEFIE. One hundred and eighty-three (56.8%) received AC. Thirty-nine patients (21.3%) were treated with 4wAC for four weeks and 70 patients (38.3%) with 6wAC. There were no differences in age or comorbidity. Patients treated 6wAC presented a longer duration of symptoms before diagnosis (21 days, IQR 7-60 days vs. 7 days, IQR 1-22 days; p = 0.002). Six patients presented perivalvular abscess and all of these received 6wAC. Surgery was performed on 14 patients (35.9%) 4wAC and 34 patients (48.6%) 6wAC (p = 0.201). In-hospital mortality, one-year mortality and relapses among 4wAC and 6wAC patients were 10.3% vs. 11.4% (p = 0.851); 17.9% vs. 21.4% (p = 0.682) and 5.1% vs. 4.3% (p = 0.833), respectively. In conclusion, a four-week course of AC may be considered as an alternative regimen in NVEFIE, notably in patients with shorter duration of symptoms and those without perivalvular abscess. These results support the performance of a randomized clinical trial to evaluate the efficacy of this short regimen.

Abstract About 70 genetic studies have already addressed the need of biomarkers to predict the response of patients with rheumatoid arthritis (RA) to methotrexate (MTX) treatment. However, no genetic biomarker has yet been sufficiently validated. Here, we aimed to replicate a selection of 25 SNPs in the largest collection of patients up to date, which consisted of 915 patients treated with MTX. The change in disease activity (measured as ΔDAS28) from baseline was considered the primary outcome. In addition, response according to widely used criteria (EULAR) was taken as secondary outcome. We considered consistency between outcomes, P values accounting for the number of SNPs, and independence from potential confounders for interpretation of the results. Only the rs1801394 SNP in MTRR fulfilled the high association standards. Its minor allele was associated with less improvement than the major allele according to ΔDAS28 (p = 0.0016), and EULAR response (p = 0.004), with independence of sex, age, baseline DAS28, smoking, seropositivity, concomitant corticosteroid use or previous treatments. In addition, previous evidence suggests the association of this SNP with response to MTX in another autoimmune disease, juvenile idiopathic arthritis, and with high intracellular folate levels, which could contribute to poor response.

Resumen: La angiografía coronaria por tomografía computarizada (ACTC) es considerada la prueba no invasiva de mayor sensibilidad para la detección de enfermedad arterial coronaria, con un valor predictivo negativo de entre el 97 al 99%.Presentamos un caso de rotura de pared libre de ventrículo izquierdo como complicación de infarto agudo de miocardio, cuyo diagnóstico fue diferido debido al resultado falso negativo de una angiografía coronaria mediante tomografía computarizada.Creemos que este caso ilustra posibles limitaciones en cuanto a la expansión de las indicaciones de la ACTC y la importancia del volumen en la interpretación correcta de la misma. Abstract: Computed tomography coronary angiography (CTCA) is considered to be the highest sensitivity, non-invasive test for the diagnosis of coronary artery disease, with a negative predictive value of 97 to 99%.The case is presented of a ventricular free wall rupture after myocardial infarction, with a delayed diagnosis due to a false negative CTCA result.We believe that this case highlights possible limitations of widening CTCA indications and the importance of experience in the correct interpretation of the test. Palabras clave: Angiografía coronaria por tomografía computarizada, Imagen coronaria, Infarto de miocardio, Complicaciones mecánicas, Keywords: Computed tomography coronary angiography, Coronary artery imaging, Myocardial infarction, Mechanical complications

Papillary fibroelastomas are rare benign primary cardiac tumors that usually grow depending on the left heart valves. The pulmonary valve is rarely involved, with only 7% of cases described on it. Most of patients are asymptomatic but these tumors are responsible for life-threatening complications. We present a singular case of papillary fibroelastoma depending on the pulmonary valve in a young woman detected by echocardiography which was surgically removed with an uneventful recovery. Resumen: Los fibroelastomas papilares son unos tumores cardíacos primarios que normalmente crecen dependiendo de las válvulas cardíacas izquierdas. La válvula pulmonar rara vez se ve involucrada, estando presente en tan solo un 7% de los casos descritos. La mayoría de los pacientes están asintomáticos, pero estos tumores son responsables de las complicaciones potencialmente mortales. Se presenta un caso singular de fibroelastoma papilar sobre válvula pulmonar en una mujer joven detectado por ecocardiografía y tratado mediante excisión quirúrgica con un postoperatorio sin complicaciones. Keywords: Cardiac tumors, Echocardiography, Pulmonary valve, Heart valve repair, Palabras clave: Tumores cardíacos, Ecocardiografía, Válvula pulmonar, Reparación valvular

Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. Deficits in hippocampal synaptic plasticity have been involved in the HD memory impairment. Several studies show that prostaglandin E2 (PGE2) EP2 receptor stimulates synaptic plasticity and memory formation. However, this role was not explored in neurodegenerative diseases. Here, we investigated the capacity of PGE2 EP2 receptor to promote synaptic plasticity and memory improvements in a model of HD, the R6/1 mice, by administration of the agonist misoprostol. We found that misoprostol increases dendritic branching in cultured hippocampal neurons in a brain-derived neurotrophic factor (BDNF)-dependent manner. Then, we implanted an osmotic mini-pump system to chronically administrate misoprostol to R6/1 mice from 14 to 18 weeks of age. We observed that misoprostol treatment ameliorates the R6/1 long-term memory deficits as analyzed by the T-maze spontaneous alternation task and the novel object recognition test. Importantly, administration of misoprostol promoted the expression of hippocampal BDNF. Moreover, the treatment with misoprostol in R6/1 mice blocked the reduction in the number of PSD-95 and VGluT-1 positive particles observed in hippocampus of vehicle-R6/1 mice. In addition, we observed an increase of cAMP levels in the dentate ` of WT and R6/1 mice treated with misoprostol. Accordingly, we showed a reduction in the number of mutant huntingtin nuclear inclusions in the dentate gyrus of R6/1 mice. Altogether, these results suggest a putative therapeutic effect of PGE2 EP2 receptor in reducing cognitive deficits in HD.

Se analiza la forma en que México aplica la normativa y otras estrategias de manejo, para la protección de los humedales costeros y aves de humedal de la Península de Yucatán según el Plan Estratégico Ramsar 2009-2015, específicamente en dos de sus estrategias. Se analiza los criterios de regulación de los Programas de Manejo de Áreas Naturales Protegidas y Ordenamientos Ecológicos Territoriales identificando los aspectos científicos robustos en los que se fundamentan, así como en sus deficiencias bajo el concepto de integridad ecológica. En los resultados se observa: a) la necesidad de homogenizar el uso del término integridad en los instrumentos legales, b) crear una estructura jerárquica espacial de estrategias de manejo que favorezca la conectividad, c) reforzar en la delimitación de áreas de amortiguamiento de humedales y hábitats críticos de aves, d) incorporar reglas que protejan la heterogeneidad biológica espacio-temporal, los procesos ecológicos y las redes tróficas, y e) diseñar un reglamento para la restauración de humedales. Se concluye que el escenario normativo aplicable a la conservación de estos ecosistemas en México es aún muy ineficiente y que es necesario incorporar una visión sistémica para proteger estos ecosistemas. Se incluyen además, nueve recomendaciones para su mejoramiento.

La generación de nanociencia se presenta estable a lo largo de un período de tiempo, a diferencia de las patentes, cuya trayectoria en el tiempo parece ser aleatoria. El dominio de Estados Unidos, tanto en la generación de nanociencia como de patentes de nanotecnología, es evidente. A pesar de ello, por el lado de la esfera de publicaciones, China sobrepasa a Estados Unidos en cantidad de artículos publicados sobre nanociencia. Por otro lado, en el aspecto de las patentes, Japón y Corea del Sur parecen querer competir con Estados Unidos en materia de nanotecnología.

Patients with rheumatoid arthritis (RA) have an increased mortality rate that is associated with the presence of RA-specific autoantibodies in many studies. However, the relative role of rheumatoid factor (RF), anti-CCP antibodies and the most recently established RA-autoantibodies, directed against carbamylated proteins (anti-CarP antibodies), is unclear. Here, we have assessed the role of these three antibodies in 331 patients with established RA recruited from 2001 to 2009 and followed until November 2015. During this time, 124 patients died (37.5%). This death rate corresponds to a mortality rate 1.53 (95% CI 1.26 to 1.80) folds the observed in the reference population. We used for analysis of all-cause mortality the Cox proportional hazard regression model with adjustment for age, sex and smoking. It showed a trend for association with increased mortality of each of the three RA autoantibodies in antibody-specific analysis (hazards ratio (HR) from 1.37 to 1.79), but only the HR of the anti-CarP antibodies was significant (HR = 1.79, 95% CI 1.23 to 2.61, p = 0.002). In addition, the multivariate analysis that included all autoantibodies showed a marked decrease in the HR of RF and of anti-CCP antibodies, whereas the HR of anti-CarP remained significant. This increase was specific of respiratory system causes of death (HR = 3.19, 95% CI 1.52 to 6.69, p = 0.002). Therefore, our results suggest a specific relation of anti-CarP antibodies with the increased mortality in RA, and drive attention to their possible connection with respiratory diseases.

El Ordenamiento Ecológico Marino (OEM) ha sido adoptado en México como el instrumento de política ambiental que atiende las problemáticas marinas y da certidumbre a las actividades inherentes que ahí se desarrollan. Sin embargo, su ejecución aún representa un desafío para el gobierno, quién ha solicitado la participación activa del gremio científico en la elaboración de propuestas para mejorar los planes operativos de los OEM: los Programas de Ordenamiento Ecológico Marino (POEM). En el presente artículo se revisa el aporte de la academia, la construcción de los POEM y los retos que prevalecen para lograr una implementación efectiva de los OEM. México es un país con tantas lecciones aprendidas como por aprender. Futuras agendas de investigación debieran trascender a un siguiente nivel de discusión, donde se priorice articular acciones que busquen: 1) armonizar los OEM con otros instrumentos de manejo costero y marino, 2) promover y desarrollar un manejo adaptativo a través de indicadores de monitoreo y evaluación, 3) hacer más eficiente la planeación socialmente inclusiva, y 4) favorecer el desarrollo de capacidades a todos los niveles de decisión sobre el manejo integral de la zona costera y marina.

Biological age is not always concordant with chronological age and the departures are of interest for understanding how diseases and environmental insults affect tissue function, organismal health, and life expectancy. The best-known biological age biomarker is telomere length, but there are more accurate biomarkers as the recently developed based in epigenetic, transcriptomic, or biochemical changes. The most accurate are the epigenetic biomarkers based on specific changes in DNA methylation referred as DNA methylation age measures (DmAM). Here, we have developed and validated a new DmAM that addresses some limitations of the previously available. The new DmAM includes the study in whole blood (WB) of 8 CpG sites selected as the most informative on a training set of 390 healthy subjects. The 8 CpG DmAM showed better accuracy than other DmAM based in few CpG in an independent validation set of 335 subjects. Results were not significantly influenced by sex, smoking, or variation in blood cell subpopulations. In addition, the new 8 CpG DmAM was amenable to study in a single multiplex reaction done with methylation-sensitive single-nucleotide primer extension (MS-SNuPE), a methodology based on commercially available reagents and run in capillary electrophoresis sequencers. In this way, the high cost of DNA methylation microarrays or of a pyrosequencer, which are needed for alternative DmAM, was avoided. Performance of the DmAM with MS-SNuPE was assessed in a set of 557 donors, showing high call rate (>97%), low CV (

Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG) polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI). First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi). We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p.) during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN), a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.

The objective of the present work was to assess the odoriferous volatile organic compounds depuration efficiency of an experimental nonthermal plasma coupled to a catalytic system used for odor abatement of real emissions from a leachate thermal drying plant installed in an urban solid waste landfill. VOC screening was performed by means of HRGC-MS analysis of samples taken at the inlet and at the outlet of the nonthermal plasma system. Odor concentration by means of dynamic olfactometry, total organic carbon, mercaptans, NH3, and H2S were also determined in order to assess the performance of the system throughout several days. Three plasma frequencies (100, 150, and 200 Hz) and two catalyst temperatures (150°C and 50°C) were also tested. Under conditions of maximum capacity of the treatment system, the results show VOC depuration efficiencies around 69%, with average depuration efficiencies between 44 and 95% depending on the chemical family of the substance. Compounds belonging to the following families have been detected in the samples: organic acids, alcohols, ketones, aldehydes, pyrazines, and reduced sulphur compounds, among others. Average total organic carbon removal efficiency was 88%, while NH3 and H2S removal efficiencies were 88% and 87%, respectively, and odor concentration abatement was 78%.

Only a few genetic studies have been carried out to date in Bolivia. However, some of the most important (pre)historical enclaves of South America were located in these territories. Thus, the (sub)-Andean region of Bolivia was part of the Inca Empire, the largest state in Pre-Columbian America. We have genotyped the first hypervariable region (HVS-I) of 720 samples representing the main regions in Bolivia, and these data have been analyzed in the context of other pan-American samples (>19,000 HVS-I mtDNAs). Entire mtDNA genome sequencing was also undertaken on selected Native American lineages. Additionally, a panel of 46 Ancestry Informative Markers (AIMs) was genotyped in a sub-set of samples. The vast majority of the Bolivian mtDNAs (98.4%) were found to belong to the main Native American haplogroups (A: 14.3%, B: 52.6%, C: 21.9%, D: 9.6%), with little indication of sub-Saharan and/or European lineages; however, marked patterns of haplogroup frequencies between main regions exist (e.g. haplogroup B: Andean [71%], Sub-Andean [61%], Llanos [32%]). Analysis of entire genomes unraveled the phylogenetic characteristics of three Native haplogroups: the pan-American haplogroup B2b (originated ∼21.4 thousand years ago [kya]), A2ah (∼5.2 kya), and B2o (∼2.6 kya). The data suggest that B2b could have arisen in North California (an origin even in the north most region of the American continent cannot be disregarded), moved southward following the Pacific coastline and crossed Meso-America. Then, it most likely spread into South America following two routes: the Pacific path towards Peru and Bolivia (arriving here at about ∼15.2 kya), and the Amazonian route of Venezuela and Brazil southwards. In contrast to the mtDNA, Ancestry Informative Markers (AIMs) reveal a higher (although geographically variable) European introgression in Bolivians (25%). Bolivia shows a decreasing autosomal molecular diversity pattern along the longitudinal axis, from the Altiplano to the lowlands. Both autosomes and mtDNA revealed a low impact (1-2%) of a sub-Saharan component in Bolivians.