Masa intraventricular en el contexto de disfunción ventricular: diagnóstico diferencial

We present a clinical case of an intracardiac mass in the context of left ventricular dysfunction in a patient without anticoagulant treatment, with the challenge of making an adequate differential diagnosis without any other tool than the transthoracic echocardiogram.Se presenta un caso clínico sobre una masa intracardíaca en el contexto de disfunción ventricular en un paciente sin tratamiento anticoagulante, con el reto adicional de realizar un adecuado diagnóstico diferencial sin otra herramienta que no sea la ecocardiografía transtorácica (ETT)

Molecular Insights into the Regulation of 3-Phosphoinositide-Dependent Protein Kinase 1 : Modeling the Interaction between the Kinase and the Pleckstrin Homology Domains

The 3-phosphoinositide-dependent protein kinase 1 (PDK1) K465E mutant kinase can still activate protein kinase B (PKB) at the membrane in a phosphatidylinositol-3,4,5-trisphosphate (PIP3, PtdIns(3,4,5)P3) independent manner. To understand this new PDK1 regulatory mechanism, docking and molecular dynamics calculations were performed for the first time to simulate the wild-type kinase domain-pleckstrin homology (PH) domain complex with PH-in and PH-out conformations. These simulations were then compared to the PH-in model of the KD-PH(mutant K465E) PDK1 complex. Additionally, three KD-PH complexes were simulated, including a substrate analogue bound to a hydrophobic pocket (denominated the PIF-pocket) substrate-docking site. We find that only the PH-out conformation, with the PH domain well-oriented to interact with the cellular membrane, is active for wild-type PDK1. In contrast, the active conformation of the PDK1 K465E mutant is PH-in, being ATP-stable at the active site while the PIF-pocket is more accessible to the peptide substrate. We corroborate that both the docking-site binding and the catalytic activity are in fact enhanced in knock-in mouse samples expressing the PDK1 K465E protein, enabling the phosphorylation of PKB in the absence of PIP3binding

Un curioso hallazgo extracardíaco en un paciente con pericarditis aguda

Extracardiac findings are relatively common on transthoracic echocardiography. We present a clinical case in which the “routine” echocardiography for pericarditis allowed to diagnose a liver abscess and solve the patient’s problem. This case demonstrates the importance of paying attention to everything that can be seen in the echocardiogram image.Es relativamente frecuente encontrar hallazgos extracardíacos en la ecocardiografía transtorácica. Se presenta un caso clínico en el que la ecocardiografía “rutinaria” por pericarditis permitió hacer el diagnóstico de un absceso hepático y resolver el problema del paciente. Este caso demuestra la importancia de prestar atención a todo lo que se pueda ver en la imagen de la ecocardiografía

Multiomics and eXplainable artificial intelligence for decision support in insulin resistance early diagnosis: A pediatric population-based longitudinal study

Supplementary Material: https://sci2s.ugr.es/MultiOmics_IR_PredPediatric obesity can drastically heighten the risk of cardiometabolic alterations later in life, with insulin resistance standing as the cornerstone linking adiposity to the increased cardiovascular risk. Puberty has been pointed out as a critical stage after which obesity-associated insulin resistance is more difficult to revert. Timely prediction of insulin resistance in pediatric obesity is therefore vital for mitigating the risk of its associated comorbidities. The construction of effective and robust predictive systems for a complex health outcome like insulin resistance during the early stages of life demands the adoption of longitudinal designs for more causal inferences, and the integration of factors of varying nature involved in its onset. In this work, we propose an eXplainable Artificial Intelligence-based decision support pipeline for early diagnosis of insulin resistance in a longitudinal cohort of 90 children. For that, we leverage multi-omics (genomics and epigenomics) and clinical data from the pre-pubertal stage. Different data layers combinations, pre-processing techniques (missing values, feature selection, class imbalance, etc.), algorithms, training procedures were considered following good practices for Machine Learning. SHapley Additive exPlanations were provided for specialists to understand both the decision-making mechanisms of the system and the impact of the features on each automatic decision, an essential issue in high-risk areas such as this one where system decisions may affect people’s lives. The system showed a relevant predictive ability (AUC and G-mean of 0.92). A deep exploration, both at the global and the local level, revealed promising biomarkers of insulin resistance in our population, highlighting classical markers, such as Body Mass Index z-score or leptin/adiponectin ratio, and novel ones such as methylation patterns of relevant genes, such as HDAC4, PTPRN2, MATN2, RASGRF1 and EBF1. Our findings highlight the importance of integrating multi-omics data and following eXplainable Artificial Intelligence trends when building decision support systemsDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, ‘‘José Mataix Verdú’’ Institute of Nutrition and Food Technology (INYTA) and Center of Biomedical Research, University of Granada, Granada, 18071, Spai

Liraglutide Improves Forced Vital Capacity in Individuals With Type 2 Diabetes: Data From the Randomized Crossover LIRALUNG Study

To evaluate the effect of liraglutide, a glucagon-like peptide 1 receptor agonist, on pulmonary function and serum levels of surfactant protein D (SP-D) in type 2 diabetes. A double-blind, randomized, crossover, placebo-controlled clinical trial comprising 76 patients with a baseline forced expiratory volume in 1 s <90% of that predicted. Liraglutide was administered for 7 weeks (2 weeks of titration plus 5 weeks at 1.8 mg daily). This short duration was intentional to minimize weight loss as a potential confounding factor. Serum level of SP-D was used as a biomarker of alveolar-capillary barrier integrity. Liraglutide exerted a positive impact on forced vital capacity (FVC) in comparison with placebo (ΔFVC 5.2% of predicted [from 0.8 to 9.6]; P = 0.009). No differences in the other pulmonary variables were observed. Participants under liraglutide treatment also experienced a decrease in serum SP-D (P = 0.038). The absolute change in FVC correlated with final serum SP-D in participants receiving liraglutide (r = −0.313, P = 0.036). Stepwise multivariate regression analysis showed that final serum SP-D independently predicted changes in FVC. In conclusion, liraglutide increased FVC in patients with type 2 diabetes. This effect was associated with a significant decrease of circulating SP-D, thus pointing to a beneficial effect in the alveolar-capillary function.CIBERDEM and CIBEROBN are initiatives of Instituto de Salud Carlos III (PI 15/00260 and PI 18/00964). The drugs under study were supplied by Novo Nordisk at the request of the sponsor of the study expressly for the clinical trial, with Novo Nordisk taking responsibility for the manufacture, packaging, and labeling

Current and future interactions between nature and society

One hundred per cent of the natural units of analysis will continue to be negatively affected, with a concomitant decrease in natures contributions to people, given current trends (business as usual), though the magnitude and exact mechanism of the individual drivers will vary by driver and unit of analysis (established but incomplete){5.4}. For example, tropical moist and dry forest and coastal mangroves will continue to exhibit a decline due to land use change regardless of the scenarios considered, but different local factors (agriculturalization and urbanization, respectively) will be involved (well established) {5.4.1, 5.4.11}. Additionally, some drivers will affect units of analysis differently. Empirical evidence indicates differential effects of climate change: boreal forest is extending northward {5.4.2}, while tundra is diminishing in land area (established but incomplete) {5.4.3}. Thus, some drivers, and their relative roles, will need to be further refined on a local scale and with respect to their proximate factors.2. Multiple drivers will act in synergy and further produce biodiversity loss and impact nature?s contributions to people in most of the units of analysis for the Americas (established but incomplete){5.4}. Climate change, combined with other drivers, is predicted to account for an increasingly larger proportion of biodiversity loss in the future, in both terrestrial and aquatic ecosystems {5.3}. Forest fragmentation, climate change and industrial development increase risk of biodiversity and nature?s contributions to people loss i.e. dry forest unit of analysis {5.4.1.2}. Predictions on invasive species and climate change indicates an increase in habitable areas and their potential impacts on different units of analysis {5.3}.3. Changes in temperature, precipitation regime and extreme climate events are predicted to impact all units of analysis in the Americas (well established) {5.4}. Climate change and the potential impacts on tropical dry forests by changing the frequency of wildfires; change in forest structure and functional composition in the Amazon tropical moist forest; extreme drought events changing nature?s contributions to people in the Amazon region; insect outbreaks and changes in albedo are predicted to significantly impact temperate, boreal and tundra units of analysis, affecting society and indigenous communities and well-being {5.4}.4. Thresholds, or tipping points (conditions resulting in rapid and potentially irreversible changes) may have already been exceeded for some ecosystems and are likely for others (established but incomplete). For instance, it is considered more likely than not that such a threshold has already been passed in the cryosphere with respect to summer sea ice (established but incomplete) {5.4.12}. Model simulations indicate changes in forest structure and species distribution in the Amazon forest in response to global warming and change in precipitation patterns (forest die-back) (established but incomplete) {5.4.1}. So too, a 4oC increase in global temperatures is predicted to likely cause widespread die off of boreal forest due to greater susceptibility to disease {5.4.2} and global temperature increases may have already started persistent thawing of the permafrost {5.4.3}. Under 4°C warming, widespread coral reef mortality is expected with significant impacts on coral reef ecosystems {5.4.11}. Sea surface water temperature increase will cause a reduction of sea grass climatic niche: those populations under seawater surface temperature thresholds higher than the temperature ranges required by the species could become extinct by 2100 with concomitant loss of ecosystem services.IPBES/6/INF/4/Rev.15415. Changes in nature and nature?s contributions to people in most units of analysis are increasingly driven by causal interactions between distant places (i.e. telecouplings) (well established) {5.6.3}, thus scenarios and models that incorporate telecouplings will better inform future policy decisions. Nature and nature?s contributions to people in telecoupled systems can be affected negatively or positively by distant causal interactions. Provision of food and medicine from wild organisms in temperate and tropical grasslands, savannas and forests of South America is being dramatically reduced due to land-use changes driven by the demand of agricultural commodities (e.g. soybeans) mainly from Europe and China. Conservation of insectivorous migratory bats in Mexico benefits pest control in agroecosystems of North America, resulting in increased yields and reduced pesticide costs. Trade policies and international agreements will thus have an increasingly strong effect on environmental outcomes in telecoupled systems.6. Policy interventions have resulted in significant land use changes at the local and regional scales and will continue to do so through 2050. These policies have affected nature?s contributions to people both positively and negatively, and provide an opportunity to manage trade-offs among nature?s contributions to people (well established) {5.4}. Land use changes are now mainly driven by high crop demand, big hydropower plans, rapid urban growth and result in a continued loss of grasslands {5.4.4, 5.4.5}. However, strategies for establishing conservation units have helped in reducing deforestation in the Brazilian Amazon from the period of 2004 to 2011 (well established) {5.4.1}. Similarly, wetland protection policies and regulation have helped reduce the conversion of wetlands in North America {5.4.7}. Policies based on command and control measures may be limited in providing effective reduction in ecosystem loss and should be complemented with policies acknowledging multiple values {5.6.3}.7. Policy interventions at vastly differing scales (from national to local) lead to successful outcomes in mitigating impacts to biodiversity (established but incomplete){5.4}. For instance, long-established governmental protections of wetlands in North America have significantly slowed and may have stopped wetland loss based on acreage {5.4.7}. In South America, where mangrove loss continues at a rate of one to two per cent, different stakeholders such as local communities and/or governments have been successful in protecting mangroves based on empowerment and shared interests in their preservation {5.4.11}.8. Pressures to nature are projected to increase by 2050, negatively affecting biodiversity as indicated by a potential reduction of the mean species abundance index. However, the magnitude of the pressures by 2050 are expected to be less under transition pathways to sustainability in comparison to the business as usual scenario (established but incomplete), {5.5}. The Global Biodiversity model projected that under the business as usual scenario mean species abundance had decreased in the Americas by approximately 30 per cent by 2010 compared to its values prior to European settlement of the New World, with historical losses primarily attributed to land transformation to agricultural uses. Using the Global Biodiversity model, there is an additional projected loss of 9.6 per cent by 2050, primarily attributed to some additional land use changes , and especially to climate change, which will steadily increase relative to other drivers considered in the model. However, under the transition pathways to sustainability of global technologies, decentralised solutions, and consumption change pathways, the projected losses are 6 per cent, 5 per cent, and 5 per cent, respectively,IPBES/6/INF/4/Rev.1542achieving a relative improvement of approximately 30 per cent to 50 per cent compared to the business as usual scenario. Under these pathways, climate change mitigation, the expansion of protected areas and the recovery of abandoned lands would significantly contribute to reducing biodiversity loss.9. Participative scenarios have proven to be a successful tool for envisioning potential futures and pathways and to embrace and integrate multiple and sometime conflicting values and their role in promoting bottom-up decision making in the face of futures uncertainties (well established) {5.3}. The use of participative approaches to develop scenarios has increased during recent years in the Americas. The inclusion of different stakeholders and their knowledges in the process of constructing potential futures has promoted a better understanding of the complexity of the social-ecological systems in which they are embedded. This has enhanced co-learning processes between all actors involved, even those normally under-represented in decision-making activities. As a result, several participative scenario exercises have motivated community-based solutions and local governance initiatives all pointing towards the development of adaptive management strategies {5.3}.10. Pathways that consider changes in societal options will lead to less pressure to nature (established but incomplete) {5.6.3}. An example is the indirect impact that shifts in urban dietary preferences have on agricultural production and expansion, and food options that are expected to continue growing into the future. Therefore, not only is there a strong connection between urbanization and economic growth, but also between affluence (and urban preferences) and the global displacement of land use particularly from high-income to low-income countries.11. Available local studies informing regional futures of nature and natures benefit to people do not allow scalability as of yet (well established) {5.3}. The challenge in expanding the findings from local studies resides in the fact that a number of comparable local studies are still not available. Information is scattered throughout the region by the use of different units, methods and scales, which prevents a local-to-regional generalization. The list of nature indicators used in studies at local scales is large and heterogeneous (well established). Even for the same indicator (e.g. biodiversity), different metrics are used (e.g. species-area curve, mean species abundance) {5.5}. In other cases, multiple indicators are used to describe different aspects of biodiversity and ecosystem services. In this latter case, synergies and trade-offs are explicitly mentioned with a clear pattern in which increasing the provision of some indicators result in the detriment of others {5.3}. For example, agriculture expansion leading to loss in biodiversity illustrates a common trend from local studies expected to continue into the future.12. There is a significant research gap in the development of models and scenarios that integrate drivers, nature, natures contributions to people and good quality of life (well established){5.3}. Models and scenarios can be powerful tools to integrate and synthesize the complex dynamics of coupled human and nature systems, and to project their plausible behaviors into the future. Most existing models and scenarios focus on the link between drivers and its impacts on nature. Few cases exist in which models or scenarios integrate the relationships between changes in nature and changes in natures contributions to people and good quality of life {5.3}. Inter-and trans-disciplinary modeling efforts will be required to address this research gap {5.3}.Fil: Klatt, Brian. Michigan State University; Estados UnidosFil: Ometto, Jean Pierre. National Institute For Space Research; BrasilFil: García Marquez, Jaime. Universität zu Berlin; AlemaniaFil: Baptiste, María Piedad. Instituto Alexander Von Humboldt; ColombiaFil: Instituto Alexander von Humboldt. Independent Consultant; CanadáFil: Acebey, Sandra Verónica. No especifíca;Fil: Guezala, María Claudia. Inter-american Institute For Global Change Research; PerúFil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pengue, Walter Alberto. Universidad Nacional de General Sarmiento; ArgentinaFil: Blanco, Mariela Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro de Estudios e Investigaciones Laborales; ArgentinaFil: Gadda, Tatiana. Universidade Tecnológica Federal Do Paraná; BrasilFil: Ramírez, Wilson. Instituto Alexander Von Humboldt; ColombiaFil: Agard, John. University Of West Indies; Trinidad y TobagoFil: Valle, Mireia. Universidad Laica Eloy Alfaro de Manabí; Ecuado

Early Diagnosis and Treatment of Purine Nucleoside Phosphorylase (PNP) Deficiency through TREC-Based Newborn Screening

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disorder, resulting in severe combined immunodeficiency. To date, PNP deficiency has been detected in newborn screening only through the use of liquid chromatography tandem mass spectrometry. We report the first case in which PNP deficiency was detected by TREC analysis

Body composition and sexual hormones for the glucose control of autoimmune diabetes in males: are they necessary to predict diabetes-related complications?

BackgroundGlucose control in diabetes is essential for avoiding diabetes-related complications.AimTo determine the impact of body composition and sexual hormones in glucose control and diabetes-related complications, in males with autoimmune diabetes.Patients and methodsThirty-nine patients with autoimmune diabetes and flash glucose monitoring were included. A morphofunctional nutritional evaluation with bioelectrical impedance vector analysis (BIVA), abdominal adipose tissue ultrasound, rectus femoris ultrasound and biochemical parameters, was performedResultsStrong, positive correlations were observed between body composition parameters, biochemical variables and sexual hormones (p&lt;0.05). Adipose tissue measured by BIVA and ultrasound was more significantly associated with glucose control (including time in range &gt;70%, glucose variability &lt;36% determined by flash glucose monitoring; p&lt;0.05) and the presence of microvascular/macrovascular complications (p&lt;0.05) than lean mass. After adjusting by the duration of diabetes, BMI, abdominal circumference, fat mass and phase angle increased the risk for microvascular complications (OR 1.32(1.00 – 1.73), OR 1.06(1.00 – 1.12), OR 1.14(1.01 – 1.20), 0R 0.3(0.10 – 0.91) respectively; for macrovascular complications: BMI OR 1.38(1.04 – 1.84) and fat mass OR 1.26(1.00 – 1.58)]. Sexual hormone levels did not influence on glucose control or the development of diabetes-related complications.ConclusionAnthrpometric parameters, especially adipose tissue, were associated with glucose control and variability determined by flash glucose monitoring. Furthermore, changes in fat and lean mass were associated with the presence of microvascular and macrovascular complications. Thus, a comprehensive nutritional evaluation might be useful for the evaluation of males with autoimmune diabetes, in order to identify patients with increased risk of complications

Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain

Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation