A systems-biology model of the tumor necrosis factor (TNF) interactions with TNF receptor 1 and 2.

MOTIVATION: Clustering enables TNF receptors to stimulate intracellular signaling. The differential soluble ligand-induced clustering behavior of TNF receptor 1 (TNFR1) and TNFR2 was modeled. A structured, rule-based model implemented ligand-independent pre-ligand binding assembly domain (PLAD)-mediated homotypic low affinity interactions of unliganded and liganded TNF receptors. RESULTS: Soluble TNF initiates TNFR1 signaling but not TNFR2 signaling despite receptor binding unless it is secondarily oligomerized. We consider high affinity binding of TNF to signaling-incompetent pre-assembled dimeric TNFR1 and TNFR2 molecules and secondary clustering of liganded dimers to signaling competent ligand-receptor clusters. Published receptor numbers, affinities and measured different activities of clustered receptors validated model simulations for a large range of receptor and ligand concentrations. Different PLAD-PLAD affinities and different activities of receptor clusters explain the observed differences in the TNF receptor stimulating activities of soluble TNF. AVAILABILITY AND IMPLEMENTATION: All scripts and data are in manuscript and supplement at Bioinformatics online. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

An optimized genetically encoded dual reporter for simultaneous ratio imaging of Ca2+ and H+ reveals new insights into ion signaling in plants.

Whereas the role of calcium ions (Ca2+ ) in plant signaling is well studied, the physiological significance of pH-changes remains largely undefined. Here we developed CapHensor, an optimized dual-reporter for simultaneous Ca2+ and pH ratio-imaging and studied signaling events in pollen tubes (PTs), guard cells (GCs), and mesophyll cells (MCs). Monitoring spatio-temporal relationships between membrane voltage, Ca2+ - and pH-dynamics revealed interconnections previously not described. In tobacco PTs, we demonstrated Ca2+ -dynamics lag behind pH-dynamics during oscillatory growth, and pH correlates more with growth than Ca2+ . In GCs, we demonstrated abscisic acid (ABA) to initiate stomatal closure via rapid cytosolic alkalization followed by Ca2+ elevation. Preventing the alkalization blocked GC ABA-responses and even opened stomata in the presence of ABA, disclosing an important pH-dependent GC signaling node. In MCs, a flg22-induced membrane depolarization preceded Ca2+ -increases and cytosolic acidification by c. 2 min, suggesting a Ca2+ /pH-independent early pathogen signaling step. Imaging Ca2+ and pH resolved similar cytosol and nuclear signals and demonstrated flg22, but not ABA and hydrogen peroxide to initiate rapid membrane voltage-, Ca2+ - and pH-responses. We propose close interrelation in Ca2+ - and pH-signaling that is cell type- and stimulus-specific and the pH having crucial roles in regulating PT growth and stomata movement.

Complete study for erectile dysfunction (CompED) improving diagnosis and treatment decision-making.

Erectile dysfunction is a condition associated with increasing age. Patient evaluation and management should follow a comprehensive, stepwise approach. The aim of this article was to report our experience with the complete study for erectile dysfunction, including intracavernous injection rigidity test, biothesiometry and colour duplex Doppler ultrasound. Data were collected and analysed prospectively. The primary end point was to determine whether treatment decision-making was eased by the CompED test. Secondary end points were to establish which clinical variables prior to the study could impact the results of the CompED test, to finally improve patient selection for the study. 187 patients were recruited, 31.2% of the patients had an axial rigidity below 50%, 28.5% had a peak systolic velocity <25 cm/s, 13.2% had an end-diastolic velocity >5cm/s and 27.5% had an abnormal biothesiometry. The factors that best predicted an abnormal result in any of the tests were age >70 years, IIEF domain A < 14 points, and previous radical prostatectomy or radiotherapy. The CompED test stands as a new alternative for the evaluation of patients with erectile dysfunction, being less time consuming, aiding in a more accurate determination of the aetiology and guiding treatment decision-making.

Railway Axle Condition Monitoring Technique Based on Wavelet Packet Transform Features and Support Vector Machines.

Railway axles are critical to the safety of railway vehicles. However, railway axle maintenance is currently based on scheduled preventive maintenance using Nondestructive Testing. The use of condition monitoring techniques would provide information about the status of the axle between periodical inspections, and it would be very valuable in the prevention of catastrophic failures. Nevertheless, in the literature, there are not many studies focusing on this area and there is a lack of experimental data. In this work, a reliable real-time condition-monitoring technique for railway axles is proposed. The technique was validated using vibration measurements obtained at the axle boxes of a full bogie installed on a rig, where four different cracked railway axles were tested. The technique is based on vibration analysis by means of the Wavelet Packet Transform (WPT) energy, combined with a Support Vector Machine (SVM) diagnosis model. In all cases, it was observed that the WPT energy of the vibration signals at the first natural frequency of the axle when the wheelset is first installed (the healthy condition) increases when a crack is artificially created. An SVM diagnosis model based on the WPT energy at this frequency demonstrates good reliability, with a false alarm rate of lower than 10% and defect detection for damage occurring in more than 6.5% of the section in more than 90% of the cases. The minimum number of wheelsets required to build a general model to avoid mounting effects, among others things, is also discussed.

An open source tool for automatic spatiotemporal assessment of calcium transients and local 'signal-close-to-noise' activity in calcium imaging data.

Local and spontaneous calcium signals play important roles in neurons and neuronal networks. Spontaneous or cell-autonomous calcium signals may be difficult to assess because they appear in an unpredictable spatiotemporal pattern and in very small neuronal loci of axons or dendrites. We developed an open source bioinformatics tool for an unbiased assessment of calcium signals in x,y-t imaging series. The tool bases its algorithm on a continuous wavelet transform-guided peak detection to identify calcium signal candidates. The highly sensitive calcium event definition is based on identification of peaks in 1D data through analysis of a 2D wavelet transform surface. For spatial analysis, the tool uses a grid to separate the x,y-image field in independently analyzed grid windows. A document containing a graphical summary of the data is automatically created and displays the loci of activity for a wide range of signal intensities. Furthermore, the number of activity events is summed up to create an estimated total activity value, which can be used to compare different experimental situations, such as calcium activity before or after an experimental treatment. All traces and data of active loci become documented. The tool can also compute the signal variance in a sliding window to visualize activity-dependent signal fluctuations. We applied the calcium signal detector to monitor activity states of cultured mouse neurons. Our data show that both the total activity value and the variance area created by a sliding window can distinguish experimental manipulations of neuronal activity states. Notably, the tool is powerful enough to compute local calcium events and 'signal-close-to-noise' activity in small loci of distal neurites of neurons, which remain during pharmacological blockade of neuronal activity with inhibitors such as tetrodotoxin, to block action potential firing, or inhibitors of ionotropic glutamate receptors. The tool can also offer information about local homeostatic calcium activity events in neurites.

EMD-Based Methodology for the Identification of a High-Speed Train Running in a Gear Operating State.

An efficient maintenance is a key consideration in systems of railway transport, especially in high-speed trains, in order to avoid accidents with catastrophic consequences. In this sense, having a method that allows for the early detection of defects in critical elements, such as the bogie mechanical components, is a crucial for increasing the availability of rolling stock and reducing maintenance costs. The main contribution of this work is the proposal of a methodology that, based on classical signal processing techniques, provides a set of parameters for the fast identification of the operating state of a critical mechanical system. With this methodology, the vibratory behaviour of a very complex mechanical system is characterised, through variable inputs, which will allow for the detection of possible changes in the mechanical elements. This methodology is applied to a real high-speed train in commercial service, with the aim of studying the vibratory behaviour of the train (specifically, the bogie) before and after a maintenance operation. The results obtained with this methodology demonstrated the usefulness of the new procedure and allowed for the disclosure of reductions between 15% and 45% in the spectral power of selected Intrinsic Mode Functions (IMFs) after the maintenance operation.

Effective Crack Detection in Railway Axles Using Vibration Signals and WPT Energy.

Crack detection for railway axles is key to avoiding catastrophic accidents. Currently, non-destructive testing is used for that purpose. The present work applies vibration signal analysis to diagnose cracks in real railway axles installed on a real Y21 bogie working on a rig. Vibration signals were obtained from two wheelsets with cracks at the middle section of the axle with depths from 5.7 to 15 mm, at several conditions of load and speed. Vibration signals were processed by means of wavelet packet transform energy. Energies obtained were used to train an artificial neural network, with reliable diagnosis results. The success rate of 5.7 mm defects was 96.27%, and the reliability in detecting larger defects reached almost 100%, with a false alarm ratio lower than 5.5%.

Dynamics and Embedded Internet of Things Input Shaping Control for Overhead Cranes Transporting Multibody Payloads.

Input shaping is an Optimal Control feedforward strategy whose ability to define how and when a flexible dynamical system defined by Ordinary Differential Equations (ODEs) and computer controlled would move into its operative space, without command induced unwanted dynamics, has been exhaustively demonstrated. This work examines the issue of Embedded Internet of Things (IoT) Input Shaping with regard to real time control of multibody oscillatory systems whose dynamics are better described by differential algebraic equations (DAEs). An overhead crane hanging a double link multibody payload has been appointed as a benchmark case; it is a multibody, multimode system. This might be worst scenario to implement Input Shaping. The reasons can be found in the wide array of constraints that arise. Firstly, the reliability of the multibody model was tested on a Functional Mock-Up Interface (FMI) with the two link payload suspended from the trolley by comparing the experimental video tapping signals in time domain faced with the signals extracted from the multibody model. The FFTs of the simulated and the experimental signal contain the same frequency harmonics only with somewhat different power due to the real world light damping in the joints. The application of this approach may be extended to other cases i.e., the usefulness of mobile hydraulic cranes is limited because the payload is supported by an overhead cable under tension that allows oscillation to occur during crane motion. If the payload size is not negligible small when compared with the cable length may introduce an additional oscillatory mode that creates a multibody double pendulum. To give the insight into the double pendulum dynamics by Lagrangian methods two slender rods as payloads are analyzed dealing with the overhead crane and a composite revolute-revolute joint is proposed to model the cable of the hydraulic crane, both assumptions facilitates an affordable analysis. This allows developing a general study of this type of multibody payloads dynamics including its normal modes, modes ratios plus ranges of frequencies expected. Input Shapers were calculated for those multimodes of vibration by convolving Specified Insensitivity (SI) shapers for each mode plus a novel Direct SI-SI shaper well suited to reduce the computational requirements, i.e., the number of the shaper taps, to carry out the convolution sum in real time by the IoT device based on a single microcontroller working as the command generator. Several comparisons are presented for the shaped and unshaped responses using both the multibody model, the experimental FMI set-up and finally a real world hydraulic crane under slewing motion commanded by an analog Joystick connected by two RF modules 802.15.4 to the IoT device that carry out the convolution sum in real time. Input Shaping improves the performances for all the cases.

The ß-cell primary cilium is an autonomous Ca2+ compartment for paracrine GABA signaling.

The primary cilium is an organelle present in most adult mammalian cells that is considered as an antenna for sensing the local microenvironment. Here, we use intact mouse pancreatic islets of Langerhans to investigate signaling properties of the primary cilium in insulin-secreting ß-cells. We find that GABAB1 receptors are strongly enriched at the base of the cilium, but are mobilized to more distal locations upon agonist binding. Using cilia-targeted Ca2+ indicators, we find that activation of GABAB1 receptors induces selective Ca2+ influx into primary cilia through a mechanism that requires voltage-dependent Ca2+ channel activation. Islet ß-cells utilize cytosolic Ca2+ increases as the main trigger for insulin secretion, yet we find that increases in cytosolic Ca2+ fail to propagate into the cilium, and that this isolation is largely due to enhanced Ca2+ extrusion in the cilium. Our work reveals local GABA action on primary cilia that involves Ca2+ influx and depends on restricted Ca2+ diffusion between the cilium and cytosol.

Estimation of R0 for the spread of SARS-CoV-2 in Germany from excess mortality.

For SARS-CoV-2, R0 calculations in the range of 2-3 dominate the literature, but much higher estimates have also been published. Because capacity for RT-PCR testing increased greatly in the early phase of the Covid-19 pandemic, R0 determinations based on these incidence values are subject to strong bias. We propose to use Covid-19-induced excess mortality to determine R0 regardless of RT-PCR testing capacity. We used data from the Robert Koch Institute (RKI) on the incidence of Covid cases, Covid-related deaths, number of RT-PCR tests performed, and excess mortality calculated from data from the Federal Statistical Office in Germany. We determined R0 using exponential growth estimates with a serial interval of 4.7 days. We used only datasets that were not yet under the influence of policy measures (e.g., lockdowns or school closures). The uncorrected R0 value for the spread of SARS-CoV-2 based on RT-PCR incidence data was 2.56 (95% CI 2.52-2.60) for Covid-19 cases and 2.03 (95% CI 1.96-2.10) for Covid-19-related deaths. However, because the number of RT-PCR tests increased by a growth factor of 1.381 during the same period, these R0 values must be corrected accordingly (R0corrected = R0uncorrected/1.381), yielding 1.86 for Covid-19 cases and 1.47 for Covid-19 deaths. The R0 value based on excess deaths was calculated to be 1.34 (95% CI 1.32-1.37). A sine-function-based adjustment for seasonal effects of 40% corresponds to a maximum value of R0January = 1.68 and a minimum value of R0July = 1.01. Our calculations show an R0 that is much lower than previously thought. This relatively low range of R0 fits very well with the observed seasonal pattern of infection across Europe in 2020 and 2021, including the emergence of more contagious escape variants such as delta or omicron. In general, our study shows that excess mortality can be used as a reliable surrogate to determine the R0 in pandemic situations.

New support roller profile design for railway wheel re-profiling process by under-floor lathes with a single cutting tool.

The wheel re-profiling is an important part of railway wheelset maintenance. Researchers and railway operators have been very concerned about how to minimize the loss of time during wheel re-profiling without decreasing safety. Avoiding wheelset disassembly means considerable time savings, while reducing wheel damage during operation. Underfloor wheel lathes are the most appropriate tool to achieve this double objective, and therefore the most used nowadays. Multi-cut tool lathes have the disadvantage of being extremely expensive. On the other hand, with single tool lathes, re-profiling is not smooth or safe enough when current convex profile support rollers are used. It is well known by the companies that during reprofiling the wheel suffers impacts/damaged. In this article, a methodology to optimize the profile of the support rollers used in underfloor single tool lathes for railway wheel re-profiling is proposed. This novel profile design will minimize damage and increase the safety of such lathes, since it proposes a greater smoothness in the process. Simulations of re-profiling process have been carried out by the finite element method showing that the designed roller profile reduces drastically the impact/damage during the operation. The impact generated between the re-profiling wheel and the rollers is avoided. Profile-optimized support rollers have been used in a real underfloor wheel lathe, showing good results.

MicroRNAs as Potential Liquid Biopsy Biomarker for Patients with Castration-Resistant Prostate Cancer.

Purpose: To identify micro-RNAs (miRNAs) expression profiles in peripheral blood plasma that could play a role as potential biomarkers in patients who progressed to castration-resistant prostate cancer (CRPC). Liquid biopsy analysis of miRNAs is a fast-developing field with a considerable likelihood to predict tumor progression and metastasis by targeting genes involved in oncogenesis. Patients and Methods: Differential expression analysis of miRNAs profile in CRPC patients was performed by creating small RNA libraries of circulating miRNAs using HiSeq2500 Illumina platform. A secondary analysis of aligned reads with miRNA identification and quantification was performed using miARmaSeq. Using the Bowtie algorithm, the selected variants were compared to reference nucleotide sequence GRCh38 and miRbase. Novel miRNA sequences were structurally analyzed using mirDeep2®. Results: A total of 16 patients with CRPC were included for analysis. Identified circulating miRNAs were hsa-miR-885-3p, hsa-miR-4467, hsa-miR-4686, hsa-miR-146a-3p, hsa-miR-6514-5p. Genes identified as regulated by these miRNAs were GPR56, BDNF, CTNND1, C17orf62, and DTNA. Conclusion: We explored the miRNA expression profile in patients with CRPC, identifying five miRNAs implicated in the regulation of genes involved in prostate cancer (PCa) oncogenesis and progression. We also found miRNA 855-3p in peripheral blood for the first time, which has a critical role in tumor growth mechanisms and higher expression profile than in healthy individuals.

Standardization of penile angle estimation with a semi-automated algorithm.

INTRODUCTION: Penile curvature (PC) refers to an abnormal bending of the main longitudinal axis of the penis. It is frequently associated to hypospadias. To date, accurate and objective evaluation of PC is not easily reproducible amongst surgeons and there are no stablished protocols on how to measure PC in a standard way and in real-time to guide intraoperative decision making. For this reason, we want to present the results of creating a semi-automated algorithm to establish a reproducible and objective assessment of PC and propose it as a standard protocol for clinical applicability using inanimate 3-D penile models. METHODS: This project consisted in two different phases. 1. Creation of an automated algorithm to estimate penile angle based on digital images. 2 Use of the algorithm to estimate penile angle on 3-D models and estimate interrater agreement using the algorithm. The algorithm was created to initially identify the geometrical centerline of the penile model to establish an automated output for angle estimation. 3-D printed penile models with known curvature angles ranging from 10 to 90° were used to test the algorithm (total of 9 penile models. These models were curved at one hinge as opposed to an arc type model. For each inanimate model, a set of 5 pictures were obtained from a lateral view at different camera angles (00, 150, 300, 450 and 600) at a standard distance of 75 cm. Angle estimation using our designed PC algorithm was performed by a total of 10 different evaluators. Inter-rater reliability analysis in using the semiautomated algorithm was performed using the inter-class correlation coefficient (ICC) with two-way mixed effect model. RESULTS: If the camera angle was greater than 30°, the absolute angle mean difference was greater than 10°. Camera angle with the smallest mean difference was at 00 with a mean difference of 7.83°. Agreement between raters showed greater variability towards the higher camera angles. Nonetheless, a high degree of between evaluator reliability was found between the measurements at different camera angles. Single measures ICC ranges from .873 to .946, p-values were all <.0001. CONCLUSION: Our results help standardize PC assessment using digital images and reduce subjectivity using an algorithm for PC estimation. Optimal camera position between 00 to 300 vertical from the penis gives the least variable and most accurate angle estimation. Future studies using algorithms will help define predictive PC cutoff values and evaluate postoperative outcomes.

Mechanical behaviour analyses of sap ascent in vascular plants.

A pure mechanical anisotropic model of a tree trunk has been developed based on the 3D finite element method. It simulates the microscopic structure of vessels in the trunk of a European beech (Fagus sylvatica) in order to study and analyse its mechanical behaviour with different configurations of pressures in the conduits of xylem and phloem. The dependence of the strains at the inner bark was studied when sap pressure changed. The comparison with previously published experimental data leads to the conclusion that a great tensile stress-or 'negative pressure'-must exist in the water column in order to achieve the measured strains if only the mechanical point of view is taken into account. Moreover, the model can help to design experiments where qualitatively knowing the strains and the purely mechanical behaviour of the tree is required.

Oncological and Functional Outcomes After Organ-Sparing Plastic Reconstructive Surgery for Penile Cancer.

OBJECTIVE: To describe oncological and functional outcomes in patients treated with reconstructive organ-sparing surgery (OSS) for squamous cell carcinoma of the penis. Plastic reconstructive OSS of the penis with a split thickness skin graft has been proposed as a treatment option for penile cancer, with the objective being preservation of physiological voiding and sexual function without comprising oncological control. MATERIALS AND METHODS: Multicenter study reporting clinicopathological data of 57 patients with malignant lesions of the penis treated with OSS and plastic reconstructive surgery with split thickness skin graft from 2007 to 2019. Health related quality of life (HRQoL) was assessed with EuroQoL-5D-3L, urinary symptoms with the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms, and erectile function with the International Index of erectile function (IIEF)-5. RESULTS: Fifty-seven patients underwent OSS reconstructive surgery. Twenty underwent glans resurfacing, 23 partial penectomy, and 14 glansectomy. Median age was 55.1 years (interquartile range [IQR] 29-90), median follow-up 55.7 months (3-149). At the time of data analysis, 6 patients had died of Squamous Cell Carcinoma (SCC) (12.5%) and 10 (17.8%) had progressed. Kaplan-Meier estimates showed a 5-year survival rate of 87.5% and a 5-year progression-free survival of 83%. We assessed HRQoL and functional outcomes in 32 patients. EuroQol 5D-3L showed a mean health status of 82.5%, median Voiding score of the ICIQ-MLTUS was 4 (IQR 1-15), and median IIEF-5 19 (IQR 10.75-25). CONCLUSION: OSS of the penis remains a safe and viable option for the treatment of SCC, ensuring a favorable appearance of the penis, preserving urinary and sexual function, with good HRQoL and without comprising oncological safety in selected cases.

Epidemiology of renal cancer in developing countries: Review of the literature.

INTRODUCTION: Renal cell carcinoma (RCC) is the ninth most common cancer in men, and the 14th most common cancer in women. It has been reported that the incidence of RCC is rising. These changes are more common in developed countries because of better screening programs and disease registry. The aim of this article is to review the epidemiology of RCC around the world. METHODS: A literature review of four databases was performed: PubMed, Embase, Lilacs, and Scielo. Studies of incidence, prevalence, mortality, and survival of RCC were taken from different countries. Studies included were published in the last 10 years. Two reviewers independently selected the studies. RESULTS: A total of 5275 references were reviewed by title and abstract. In the end, 42 references were selected for full-text review. The global incidence and prevalence of cancer vary. The highest incidence was described in North America and Northern Europe. In Canada, by 2007 the incidence was 17.9/100 000 and 10.3/100 000 in males and females, respectively. Developing countries like Colombia have fewer incidence rates, with less information in poor-income areas. CONCLUSIONS: We have seen a rise in the incidence and mortality of RCC globally. There is an association between RCC and smoking, obesity, hypertension, and socioeconomic status. Seeing the epidemiological data from some regions in developing countries and the lack of specialists in those places, it can be deduced there is underreporting of the disease that reveals the need to improve both surveillance and disease registration programs, especially in these countries.

Urological, vascular, and infectious implications of kidney transplant: a single-center experience / Complicaciones urológicas, vasculares e infecciosas del trasplante renal: experiencia en un solo centro

Introduction: Kidney transplant has improved in the last decades due to new technologies and surgical techniques. However, there are still multiple complications associated with this procedure, which can affect the function and viability of the kidney graft. Our aim was to describe the incidence of urological, vascular, and infectious complications in the 1st month after the procedure. Methods: A cross-sectional and retrospective study was carried out. Records of all patients who underwent kidney transplant from 2007 to 2017 were reviewed and data of demographic and surgical variables as well as information of vascular, urological, and infectious complications during the 1st post-operative month were registered and analyzed. Results: A total of 243 patients that required kidney transplant were assessed. The most common chronic kidney disease etiologies were: idiopathic (25.5%), glomerulopathies (24.7%), and hypertension (23.5%). Seventy patients (28.8%) presented a complication, of which 31 were urological, 27 were infectious, and 12 were vascular. In each category, the most frequent complications were the perirenal hematoma, the urinary tract infection, and renal artery stenosis, respectively. Conclusions: The prevalence of complications found in our center is similar to that reported in the literature and it is significant. It is important for medical personnel to be aware of this data to have a high level of suspicion and make an active search, as an early diagnosis and treatment of these pathologies are crucial to avoid graft loss

Introducción: El trasplante renal ha mejorado en las últimas décadas gracias a las nuevas tecnologías y técnicas quirúrgicas. Sin embargo, aún existen múltiples complicaciones asociadas a este procedimiento, que pueden afectar la función y viabilidad del injerto renal. Nuestro objetivo fue describir la incidencia de complicaciones urológicas, vasculares e infecciosas en el primer mes tras el procedimiento. Métodos: Se realizó un estudio retrospectivo de corte transversal. Se revisaron los expedientes de todos los pacientes que se sometieron a trasplante renal desde 2007 hasta 2017 y se registraron y analizaron datos de variables demográficas y quirúrgicas, así como información de complicaciones vasculares, urológicas e infecciosas durante el primer mes postoperatorio. Resultados: Se evaluaron un total de 243 pacientes que requirieron trasplante renal. Las etiologías de enfermedad renal crónica (ERC) más frecuentes fueron: idiopática (25,5%), glomerulopatías (24,7%) e hipertensión arterial (23,5%). 70 pacientes (28,8%) presentaron alguna complicación, de los cuales 31 fueron urológicos, 27 infecciosos y 12 vasculares. En cada categoría las complicaciones más frecuentes fueron el hematoma perirrenal, la infección del tracto urinario y la estenosis de la arteria renal respectivamente. Conclusiones: La prevalencia de complicaciones encontrada en nuestro centro es similar a la reportada en la literatura y es significativa. Es importante que el personal médico conozca estos datos para tener un alto nivel de sospecha y realizar una búsqueda activa, ya que el diagnóstico y tratamiento precoz de estas patologías es fundamental para evitar la pérdida del injerto.

Creation of a Pilot Surgical Program for the Comprehensive Management of Patients with Congenital Urological Malformations / Creación de un programa quirúrgico piloto para el manejo integral de pacientes con malformaciones urológicas congénitas

Objectives Congenital malformations constitute the first cause of morbidity and mortality in childhood in Latin America. That is why, since 2001, a surveillance system for congenital malformations has been implemented in Bogota - Colombia. However, despite the increase in detection, an impact on treatment has not been achieved. The present study describes our experience with a novel social program focused on congenital urologic disorders. Methods The present manuscript is a retrospective observational study. We reviewed two national databases containing patients with congenital malformations. Patients were actively contacted to verify the status of the malformations. Children in whom the malformation was confirmed were offered a free consultation with a multidisciplinary group. After screening for surgical indications, patients were scheduled for surgery. Results Between November 2018 and December 2019, 60 patients were identified. In total 44, attended the consultation; the remaining did not attend due to financial or travel limitations. The most common condition assessed was hypospadias. In total, 29 patients underwent surgery. The total cost of care was of US$ 5,800. Conclusions Active search improves attention times and reduces the burden of disease. The limitations to be resolved include optimizing the transportation of patients and their families, which is a frequent limitation to access health care.

Objetivos Las malformaciones congénitas corresponden a la principal causa de morbimortalidad en la infancia en América Latina, motivo por el cual desde el 2001 se viene implementando un sistema de vigilancia epidemiológica de malformaciones congénitas en Bogotá, Colombia. Sin embargo, a pesar del aumento en la cobertura del reporte obligatorio, no se ha logrado un impacto sobre su tratamiento. Este estudio busca mostrar nuestra experiencia con un programa integral de pacientes con malformaciones urológicas congénitas. Métodos El presente es un estudio observacional retrospectivo. Los menores con malformaciones congénitas fueron identificados en dos bases de datos nacionales que incluyen pacientes con malformaciones congénitas. Los pacientes reportados fueron contactados telefónicamente para verificar el estado actual de la malformación. A aquellos niños en quienes se les confirmó la malformación, se les ofreció de manera gratuita una consulta con un grupo multidisciplinario. Una vez confirmadas las indicaciones quirúrgicas, fueron llevados a cirugía. Resultados Se identificaron 60 pacientes entre noviembre del 2018 y diciembre de 2019. De los pacientes identificados, 44 acudieron a consulta. Los demás no asistieron por limitaciones económicas. La principal condición valorada fue hipospadias. En total, 29 pacientes fueron llevados a cirugía. El costo total de la atención de estos pacientes fue de 22 millones de pesos colombianos. Conclusiones La búsqueda activa mejora los tiempos de atención y reduce la carga de la enfermedad. Una de las limitaciones aun por resolver es optimizar el transporte de los pacientes y sus familias, que resulta una limitación frecuente para el acceso a la salud.

Effect of an intervention New Medicine Service to improve adherence in the Spanish community pharmacies: a protocol of a pragmatic randomised trial / Eficacia del Servicio de Asistencia en Nuevos Medicamentos para mejorar su adherencia en pacientes con enfermedades crónicas en farmacias comunitarias españolas: protocolo de un ensayo pragmático aleatorizado

Introduction: Non-adherence to medications is one of the challenges health systems faces. Patients with poor adherence to treatment fail to benefit from effective medication, and this is associated with reductions in quality of life, poorer outcomes, increased hospitalisations, deaths, and, consequently, higher healthcare costs. Community pharmacies are shown to be key elements in improving adherence to prescribed medications, optimising patient outcomes and increasing the efficiency of care. Objectives: (1) assess the effectiveness of the New Medicine Service (NMS) intervention delivered by community pharmacists to improve adherence to treatment in patients who have been prescribed a new medicine for a specific chronic condition; and (2) to conduct an economic evaluation of this intervention. Methods: A pragmatic randomized clinical trial at community pharmacy-level (clusters) will be performed. Patients identified in the collaborating community pharmacy as starting treatment for the following conditions, will be invited to join the study: chronic obstructive pulmonary disease, hypertension, diabetes mellitus or on an anticoagulant/antiplatelet agent. The intervention is based on the pharmacist-patient communication, aiming to assess the patient's relationship with his/her new prescription, and identify potential issues, concerns and false beliefs or expectations. Ethics and dissemination: The study protocol has been reviewed and ethics approval obtained from the regional ethics committee. The results from this study will be actively disseminated through manuscript publications and conference presentations. (AU)

Introducción: La falta de adherencia a los medicamentos es uno de los desafíos a los que se enfrentan los sistemas de salud. Los pacientes con mala adherencia al tratamiento no se benefician de la eficacia de la medicación, lo que se asocia con peor calidad de vida, aumento en hospitalizaciones y muertes y, en consecuencia, mayores costes sanitarios. Se ha demostrado que las farmacias comunitarias son elementos clave para mejorar la adherencia a los medicamentos prescritos, optimizar los resultados en pacientes con enfermedades crónicas y aumentar la eficiencia de la atención sanitaria. Objetivos: (1) evaluar la efectividad de la intervención Asistencia a Nuevos Medicamentos (ANM) administrada por farmacéuticos comunitarios para mejorar la adherencia al tratamiento en pacientes a los que se les ha recetado un nuevo medicamento para una enfermedad crónica específica; y (2) realizar una evaluación económica de esta intervención. Métodos: Se realizará un ensayo clínico pragmático aleatorizado a nivel de farmacia comunitaria (clúster). Se invitará a unirse al estudio a los pacientes identificados en la farmacia comunitaria que inicien tratamiento para: enfermedad pulmonar obstructiva crónica, hipertensión arterial, diabetes mellitus o en tratamiento con un anticoagulante/ antiagregante plaquetario. La intervención se basa en la comunicación farmacéutico-paciente, con el objetivo de evaluar la relación del paciente con su nuevo medicamento, e identificar posibles problemas, preocupaciones y falsas creencias-expectativas. Ética y difusión: Se ha obtenido el dictamen favorable del Comité de Ética de la Investigación Biomédica de Andalucía. Los resultados de este estudio se difundirán activamente a través de publicaciones y presentaciones en congresos. (AU)