Resting state networks in patients with acute disorders of consciousness after severe traumatic brain injury.

OBJECTIVES: This study aims to describe resting state networks (RSN) in patients with disorders of consciousness (DOC)s after acute severe traumatic brain injury (TBI). METHODS: Adult patients with TBI with a GCS score <8 who remained in a coma, minimally conscious state (MCS), or unresponsive wakefulness syndrome (UWS), between 2017 and 2020 were included. Blood-oxygen-level dependent imaging was performed to compare their RSN with 10 healthy volunteers. RESULTS: Of a total of 293 patients evaluated, only 13 patients were included according to inclusion criteria: 7 in coma (54%), 2 in MCS (15%), and 4 (31%) had an UWS. RSN analysis showed that the default mode network (DMN) was present and symmetric in 6 patients (46%), absent in 1 (8%), and asymmetric in 6 (46%). The executive control network (ECN) was present in all patients but was asymmetric in 3 (23%). The right ECN was absent in 2 patients (15%) and the left ECN in 1 (7%). The medial visual network was present in 11 (85%) patients. Finally, the cerebellar network was symmetric in 8 patients (62%), asymmetric in 1 (8%), and absent in 4 (30%). CONCLUSIONS: A substantial impairment in activation of RSN is demonstrated in patients with DOC after severe TBI in comparison with healthy subjects. Three patterns of activation were found: normal/complete activation, 2) asymmetric activation or partially absent, and 3) absent activation.

Regorafenib in patients with metastatic colorectal cancer in Spain: from clinical trials to real-world evidence.

Aim: To describe the evolution of regorafenib use, since its approval, in patients with previously treated metastatic colorectal cancer (mCRC) in routine clinical practice in Spain. Methods: We extracted patient characteristics, dosing, safety and efficacy data for the Spanish cohorts of the CORRECT and CONSIGN trials, and the real-world CORRELATE study. Results: The Spanish cohorts represented 10.7-13.8% of the global cohorts. Efficacy and safety in the Spanish cohorts reflected findings from the global cohorts, with evidence of a flexible dosing approach being adopted in routine clinical practice. Conclusion: Regorafenib use in patients with mCRC has evolved in the real-world setting, emphasizing the need for further research evaluating dosing patterns that can optimize clinical outcomes in these patients.Clinical trial registration: The CORRECT trial is registered at ClinicalTrials.gov, number NCT01103323; the CONSIGN trial is registered at ClinicalTrials.gov, number NCT01538680; the CORRELATE study is registered at ClinicalTrials.gov, number NCT02042144.

Bowel cancer (also called colorectal cancer) affects the large bowel, including the colon and rectum. Approximately one in ten patients with advanced bowel cancer that has spread to other areas of the body (metastatic bowel cancer) survive 5 years after diagnosis or the start of treatment.Regorafenib is a treatment for patients with advanced bowel cancer that has continued to spread after receiving other treatments. It can slow down cancer growth, as shown in three international studies (CORRECT, CONSIGN and CORRELATE). In Spain, bowel cancer is the most common type of cancer and the cancer that causes the second most deaths. This study describes how the use of regorafenib in Spain has changed since it was approved in 2012, by looking at the patients from Spain who made up 11­14% of the participants in the three international studies.The CORRECT trial that compared regorafenib with a non-therapeutic placebo and the CONSIGN trial of regorafenib alone showed that treatment with regorafenib prolonged life and was well tolerated in patients with metastatic bowel cancer who had previously received or were not suitable to receive other treatments. The CORRELATE study showed that in the real world (i.e., outside of a controlled clinical trial), patients are sometimes prescribed regorafenib at lower starting doses than the recommended dose, without an apparent overall effect on how well regorafenib works or side effects. In the future, it will be important to continue researching how doctors prescribe regorafenib in daily clinical practice in Spain.

Humanoid Head Camera Stabilization Using a Soft Robotic Neck and a Robust Fractional Order Controller.

In this paper, a new approach for head camera stabilization of a humanoid robot head is proposed, based on a bio-inspired soft neck. During walking, the sensors located on the humanoid's head (cameras or inertial measurement units) show disturbances caused by the torso inclination changes inherent to this process. This is currently solved by a software correction of the measurement, or by a mechanical correction by motion cancellation. Instead, we propose a novel mechanical correction, based on strategies observed in different animals, by means of a soft neck, which is used to provide more natural and compliant head movements. Since the neck presents a complex kinematic model and nonlinear behavior due to its soft nature, the approach requires a robust control solution. Two different control approaches are addressed: a classical PID controller and a fractional order controller. For the validation of the control approaches, an extensive set of experiments is performed, including real movements of the humanoid, different head loading conditions or transient disturbances. The results show the superiority of the fractional order control approach, which provides higher robustness and performance.

A Novel Experimental Apparatus for Characterizing Flow Regime in Mechanically Stirred Tanks through Force Sensors.

Pressure fluctuations in a mixing tank can provide valuable information about the existing flow regime within the tank, which in turn influences the degree of mixing that can be achieved. In the present work, we propose a prototype for identifying the flow regime in mechanically stirred tanks equipped with four vertical baffles through the characterization of pressure fluctuations. Our innovative proposal is based on force sensors strategically placed in the baffles of the mixing tank. The signals coming from the sensors are transmitted to an electronic module based on an Arduino UNO development board. In the electronic module, the pressure signals are conditioned, amplified and sent via Bluetooth to a computer. In the computer, the signals can be plotted or stored in an Excel file. In addition, the proposed system includes a moving average filtering and a hierarchical bottom-up clustering analysis that can determine the real-time flow regime (i.e., the Reynolds number, Re) in which the tank was operated during the mixing process. Finally, to demonstrate the versatility of the proposed prototype, experiments were conducted to identify the Reynolds number for different flow regimes (static, laminar, transition and turbulent), i.e., 0≤Re≤ 42,955. Obtained results were in agreement with the prevailing consensus on the onset and developed from different flow regimes in mechanically stirred tanks.

Adaptive state restricted barrier Lyapunov-based control of a Stewart platform used as ankle-controlled mobilizer.

In this research project, a closed-chain robotic active ankle orthosis with six degrees of freedom is designed, constructed, numerically valued, instrumented, and experimentally validated. The mechanical arrangement to implement the orthosis corresponds to a six-legged Stewart platform. An adaptive gain control strategy with state constraints based on a state-dependent gains control (that behaves as a diverging function as the states approach the state restrictions) operates the device's motion. The convergence to an invariant positive set centered at the origin of the tracking error space is validated using the stability analysis based on the second method of Lyapunov, with the implementation of a state barrier Lyapunov-like function. The ultimate boundedness of the tracking error is proven with an endorsed gains adjustment method leading to a reachable minimum size of the ultimate bound. Hence, the impact of the state constraints and the formal reason for applying the controller on the suggested orthosis are all established. The orthosis is also controlled using a conventional state feedback strategy to assess the tracking error for an external disturbance and contrast its performance with the proposed control approach. The technology is tested on a few carefully chosen volunteers, successfully limiting the range of motion within a pre-defined region based on the scope of movement reported by patients with ankle illnesses discovered in the literature. Based on a unique mechatronic device, the created system offers a fresh approach to treating this class of impairments.

PatagoniaMet: A multi-source hydrometeorological dataset for Western Patagonia.

Western Patagonia (40-56°S) is a clear example of how the systematic lack of publicly available data and poor quality control protocols have hindered further hydrometeorological studies. To address these limitations, we present PatagoniaMet (PMET), a compilation of ground-based hydrometeorological data (PMET-obs; 1950-2020), and a daily gridded product of precipitation and temperature (PMET-sim; 1980-2020). PMET-obs was developed considering a 4-step quality control process applied to 523 hydrometeorological time series obtained from eight institutions in Chile and Argentina. Following current guidelines for hydrological datasets, several climatic and geographic attributes were derived for each catchment. PMET-sim was developed using statistical bias correction procedures, spatial regression models and hydrological methods, and was compared against other bias-corrected alternatives using hydrological modelling. PMET-sim was able to achieve Kling-Gupta efficiencies greater than 0.7 in 72% of the catchments, while other alternatives exceeded this threshold in only 50% of the catchments. PatagoniaMet represents an important milestone in the availability of hydro-meteorological data that will facilitate new studies in one of the largest freshwater ecosystems in the world.

The influence of cardiac arrhythmias on the detection of heartbeats in the photoplethysmogram: benchmarking open-source algorithms.

Objective.Cardiac arrhythmias are a leading cause of mortality worldwide. Wearable devices based on photoplethysmography give the opportunity to screen large populations, hence allowing for an earlier detection of pathological rhythms that might reduce the risks of complications and medical costs. While most of beat detection algorithms have been evaluated on normal sinus rhythm or atrial fibrillation recordings, the performance of these algorithms in patients with other cardiac arrhythmias, such as ventricular tachycardia or bigeminy, remain unknown to date.Approach. ThePPG-beatsopen-source framework, developed by Charlton and colleagues, evaluates the performance of the beat detectors namedQPPG,MSPTDandABDamong others. We applied thePPG-beatsframework on two newly acquired datasets, one containing seven different types of cardiac arrhythmia in hospital settings, and another dataset including two cardiac arrhythmias in ambulatory settings.Main Results. In a clinical setting, theQPPGbeat detector performed best on atrial fibrillation (with a medianF1score of 94.4%), atrial flutter (95.2%), atrial tachycardia (87.0%), sinus rhythm (97.7%), ventricular tachycardia (83.9%) and was ranked 2nd for bigeminy (75.7%) behindABDdetector (76.1%). In an ambulatory setting, theMSPTDbeat detector performed best on normal sinus rhythm (94.6%), and theQPPGdetector on atrial fibrillation (91.6%) and bigeminy (80.0%).Significance. Overall, the PPG beat detectorsQPPG,MSPTDandABDconsistently achieved higher performances than other detectors. However, the detection of beats from wrist-PPG signals is compromised in presence of bigeminy or ventricular tachycardia.

Environmental risk management: A participatory diagnosis from a rural school in Colombia.

The rural population is potentially exposed to several environmental risks. Environmental risk management is a recurring challenge in rural educational communities that are far from large urban areas. Assessing and identifying the knowledge on prevention and response to environmental risks and natural disasters is fundamental for planning and designing educational programs for communities to face disasters. This article presented the practical application of a participatory methodology to obtain information about the knowledge and experience in the prevention and attention of environmental threats and natural disasters in the rural school Las Huacas, village of Quintana, municipality of Popayán, in the region of Cauca, Colombia. The diagnosis methodology consisted of three phases: preparatory, fieldwork and analytical. The participatory diagnosis allowed the construction of instruments and tools for social interaction, the conduction of dynamic workshops and the systematisation of the collected information. The results evidenced the lack of knowledge on environmental disasters and how parents and children must face them. The absence of communication facilities implied a high degree of vulnerability, which was compensated with the awareness, commitment and participation in the processes led by the educational community. The next challenge is the participatory construction of a scholar environmental risk-management plan supported on appropriated information and communication technologies. Contribution: This article presents the practical application of a participatory methodology to obtain information about the rural context and the knowledge and experience in the prevention and attention of environmental threats and natural disasters in a rural school in Cauca, Colombia.

Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the Swiss cohort.

AIMS: Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analysed recurrences in our patients after STAR. METHODS AND RESULTS: From 09.2017 to 01.2020, 20 patients (68 ± 8 y, LVEF 37 ± 15%) suffering from refractory VT were enrolled, 16/20 with a history of at least one electrical storm. Before STAR, an invasive electroanatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23 ± 2 Gy was delivered to the planning target volume (PTV). The median ablation volume was 26 mL (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in the proximity of the treated substrate in nine cases, remote from the PTV in three cases and involved a larger substrate over ≥3 LV segments in two cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR. CONCLUSION: STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude.

Preoperative tractography algorithm for safe resection of tumors located in the descending motor pathways zone.

Background: Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs. Methods: Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records. Results: Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 years (range, 19-81 years). A complete radiological resection was achieved in nine patients, a subtotal resection in five, a partial resection in three, and a biopsy in two. Histopathological diagnoses included 10 patients with high-grade glioma and nine with low-grade glioma. A total of 16 perirolandic locations (10 frontal and six frontoparietal) were recorded, as well as two in the insula and one in the basal ganglia. In 9 patients (47.3%), the lesion was in the dominant hemisphere. The median preoperative and postoperative Karnofsky Performance Scores were 78 and 80, respectively. Motor function was unchanged or improved over time in 15 cases (78.9%). Conclusion: This protocol of DTI reconstruction for glioma removal near the DMP shows good results in low-term neurological functional outcomes.

Case report: First-in-human combined low-dose whole-heart irradiation and high-dose stereotactic arrhythmia radioablation for immunosuppressive refractory cardiac sarcoidosis and ventricular tachycardia.

Background: Cardiac sarcoidosis is associated with heart failure, conduction abnormalities, and life-threatening arrhythmias including ventricular tachycardia (VT). Radiotherapy has been suggested as a treatment for extra-cardiac sarcoidosis in patients refractory to immunomodulatory treatment. Methods: The effectiveness and safety of low-dose whole-heart radiotherapy for therapy refractory cardiac sarcoidosis were evaluated in a pre- and post-intervention case report comparing the 54 months before and after treatment. Immunomodulatory low-dose whole-heart irradiation as sarcoidosis treatment consisted of a 2 × 2 Gy scheme. Additionally, high-dose single-fraction stereotactic arrhythmia radioablation of 1 × 20 Gy was applied to the pro-arrhythmic region to manage the ventricular tachycardia episodes. Cardiac sarcoidosis disease activity was measured by hypermetabolic areas on repeated fluorodeoxyglucose ([18F]FDG)-PET/computed tomography (CT) scans and by evaluating changes in ventricular tachycardia episodes before and after treatment. Results: One patient with therapy refractory progressive cardiac sarcoidosis and recurrent ventricular tachycardia was treated. The cardiac sarcoidosis disease activity showed a durable regression of inflammatory disease activity from 3 months onwards. The [18F]FDG-PET/CT scan at 54 months did not show any signs of active cardiac sarcoidosis, and a state of remission was achieved. The number of sustained VT episodes was reduced by 95%. We observed that the development of moderate aortic valve regurgitation was likely irradiation-related. No other irradiation-related adverse events occurred, and the left ventricular ejection fraction remained stable. Conclusion: We report here for the first time on the beneficial and lasting effects of combined immunomodulatory low-dose whole-heart radiotherapy and high-dose stereotactic arrhythmia radioablation in a patient with therapy refractory cardiac sarcoidosis and recurrent VT.

Dynamics of Endogenous Auxin and Its Role in Somatic Embryogenesis Induction and Progression in Cork Oak.

Somatic embryogenesis (SE) is a feasible in vitro regeneration system with biotechnological applications in breeding programs, although, in many forest species, SE is highly inefficient, mainly due to their recalcitrance. On the other hand, SE represents a valuable model system for studies on cell reprogramming, totipotency acquisition, and embryogenic development. The molecular mechanisms that govern the transition of plant somatic cells to embryogenic cells are largely unknown. There is increasing evidence that auxins mediate this transition and play a key role in somatic embryo development, although data on woody species are very limited. In this study, we analyzed the dynamics and possible role of endogenous auxin during SE in cork oak (Quercus suber L.). The auxin content was low in somatic cells before cell reprogramming, while it increased after induction of embryogenesis, as revealed by immunofluorescence assays. Cellular accumulation of endogenous auxin was also detected at the later stages of somatic embryo development. These changes in auxin levels correlated with the expression patterns of the auxin biosynthesis (QsTAR2) and signaling (QsARF5) genes, which were upregulated after SE induction. Treatments with the inhibitor of auxin biosynthesis, kynurenine, reduced the proliferation of proembryogenic masses and impaired further embryo development. QsTAR2 and QsARF5 were downregulated after kynurenine treatment. Our findings indicate a key role of endogenous auxin biosynthesis and signaling in SE induction and multiplication, as well as somatic embryo development of cork oak.

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.

Técnica quirúrgica para la reconstrucción del ligamento patelofemoral medial / Surgical technique for medial patellofemoral ligament reconstruction

La inestabilidad patelofemoral es uno de los problemas más frecuentes en pacientes jóvenes, y representa del 2 al 3% de todas las lesiones de rodilla. Significa una causa importante de morbilidad debido a la limitación de varias actividades de la vida diaria, y a largo plazo el surgimiento de artrosis. La inestabilidad patelofemoral es descripta como la deficiencia de la constricción pasiva que genera un desplazamiento lateral de la patela total o parcial de su posición normal con respecto a la tróclea. Los desórdenes patelofemorales son el resultado de una anatomía aberrante, están dados por una alteración en la alineación ósea y generan un desequilibrio biomecánico. Existen cuatro factores clásicos que generan inestabilidad patelar: patela alta, displasia troclear, alteración en la distancia (TT-TG) y excesiva inclinación patelar. Al generarse una luxación, el ligamento patelofemoral medial (LPFM) se ve afectado en al menos el 25% de los casos. El complemento diagnóstico se realiza a través de rayos X, tomografía computarizada y resonancia magnética. La restauración de la función por tratamiento quirúrgico ha mostrado resultados similares al conservador en primoluxaciones, sin embargo, se ha visto que la reconstrucción del ligamento patelofemoral medial presenta mejores resultados clínicos para el paciente. Hasta el momento, hemos intervenido diecinueve pacientes con la técnica descripta, para los cuales no hay reportada una reluxación de rótula y tienen una escala de Lysholm de 87 puntos que se encuentra dentro del parámetro "bueno".

Patellofemoral instability is one of the most frequent problems in young patients, and represents 2 to 3% of all knee injuries. It denotes an important cause of morbidity due to the limitation of various activities of daily living and in the long term the appearance of osteoarthritis. Patellofemoral instability is defined as the deficiency of passive constriction that generates a total or partial lateral displacement of the patella from its normal position with respect to the trochlea. Patellofemoral disorders are the result of an aberrant anatomy, they are given by an alteration in bone alignment and generates a biomechanical imbalance. There are four classic factors that generate patellar instability: high patella, trochlear dysplasia, alteration in distance (TT-TG) and excessive patellar inclination. When generating the dislocation, the medial patellofemoral ligament is affected in at least 25% of cases. The diagnostic complement is carried out through X-rays, computed tomography and nuclear magnetic resonance.Restoration of function surgical treatment has shown similar results to conservative treatment in primoluxations, however it has been seen that reconstruction of the medial patellofemoral ligament presents better clinical results for the patient.To date, nineteen patients we have been operated on with the technique described of whom there is no reported reluxation of the patella and who have a Lysholm scale of 85 points that is within a good parameter.

Morphological Alterations in the Early Developmental Stages of Zebrafish (Danio rerio; Hamilton 1822) Induced by Exposure to Polystyrene Microparticles.

Microplastics (MPs) are emerging pollutants of widespread concern in aquatic environments. The aim of this study was to evaluate the negative impact of pristine MPs of polystyrene of 100 µm on embryo and larvae of Danio rerio exposed to three environmentally relevant concentrations of polystyrene (3.84 × 10- 6, 3.84 × 10- 7, and 3.84 × 10- 8 g/mL). The exposure effect was evaluated through the general morphology score, biometrics, and integrated biomarker response version 2 index. No mortality was observed but the anatomical structure of fishes was affected showing pigmentation deficiency and alterations in the head region as the main affected endpoints. The general morphology score and the integrated biomarker response values were highly sensitive to address the effect of the three concentrations of MPs used here. Our results provide solid evidence of the negative impact of 100 µm pristine polystyrene MPs exposure on early stages of zebrafish.

Ansiedad, depresión, soledad y adopción del rol del cuidador de la persona en cuidado paliativo / Anxiety, depression, loneliness and role-taking in the caregiver of a person in palliative care

Introducción: Los cuidadores familiares de personas en cuidado paliativo (CP) se exponen continuamente a altas demandas de cuidado y a situaciones de angustia, lo que puede afectar su adopción del rol, ansiedad, depresión y percepción de soledad. Objetivo: Describir y correlacionar la ansiedad, depresión, soledad y adopción del rol en una muestra de cuidadores de personas en CP de Bogotá, Colombia.Materiales y métodos: Estudio cuantitativo transversal conducido en el primer semestre de 2021 con una muestra de 220 cuidadores familiares principales de personas en CP. Se usaron los instrumentos ROL, HADS y UCLA para medir la adopción del rol del cuidador, ansiedad y depresión, y soledad respectivamente. Fueron usados coeficientes de correlación de Pearson y modelos de regresión lineal para analizar la relación entre las variables. Resultados: El 75 % de las personas en CP tenían cáncer, el 63,2 % con índice de Karnofsky de 30 y con una edad promedio de 69,4 años. El 81,8 % de los cuidadores fueron mujeres, con edad promedio de 47,7 años, el 85,5 % cuida a la persona desde el momento del diagnóstico con una dedicación promedio de 20 h diarias de cuidado; además el 34,2 % se autorreportó enfermo. Los cuidadores que tuvieron menores puntajes de adopción del rol tendieron a presentar mayores niveles de ansiedad, depresión y soledad (p < 0,05). Conclusión: Se requieren intervenciones de cuidado transicional de cuidador familiar de la persona en CP dado su mayor riesgo de presentar soledad, ansiedad y depresión, que promuevan una adopción del rol satisfactoria y que, con ello, mejore los resultados en estos. (AU)

Introduction: Family caregivers of people in palliative care (PC) are continually exposed to high demands for care and situations of distress, which can affect their adoption of the role, causing anxiety, depression, and a perception of loneliness. Aim: To describe and correlate anxiety, depression, loneliness, and role adoption in a sample of caregivers of people in PC in Bogotá, Colombia. Materials and methods: A cross-sectional quantitative study was conducted in the first half of 2021 with a sample of 220 main family caregivers of people in PC. The ROL, HADS, and UCLA instruments were used to measure role-taking, anxiety, depression, and loneliness, respectively. Pearson’s correlation coefficients and linear regression models were used to analyze the relationship between variables. Results: 75 % of people in PC had cancer, 63.2 % with a Karnofsky index of 30 and a mean age of 69.4 years; 81.8 % of the caregivers were women, with an average age of 47.7 years; 85.5 % cared for the patient from the time of diagnosis, with an average dedication of 20 hours of care per day. In addition, 34.2 % self-reported illness. Caregivers who had lower role-adoption scores tended to have higher levels of anxiety, depression, and loneliness (p < 0.05). Conclusion: Transitional care interventions are needed for the family caregivers of people in PC given their greater risk of having loneliness, anxiety, and depression, to promote satisfactory role-taking and thus improve their results. (AU)

Evolutionary relationships of adenylation domains in fungi.

Non-ribosomal peptide synthetases (NRPSs) and NRPS-like enzymes are abundant in microbes as they are involved in the production of primary and secondary metabolites. In contrast to the well-studied NRPSs, known to produce non-ribosomal peptides, NRPS-like enzymes exhibit more diverse activities and their evolutionary relationships are unclear. Here, we present the first in-depth phylogenetic analysis of fungal NRPS-like A domains from functionally characterized pathways, and their relationships to characterized A domains found in fungal NRPSs. This study clearly differentiated amino acid reductases, including NRPSs, from CoA/AMP ligases, which could be divided into 10 distinct phylogenetic clades that reflect their conserved domain organization, substrate specificity and enzymatic activity. In particular, evolutionary relationships of adenylate forming reductases could be refined and explained the substrate specificity difference. Consistent with their phylogeny, the deduced amino acid code of A domains differentiated amino acid reductases from other enzymes. However, a diagnostic code was found for α-keto acid reductases and clade 7 CoA/AMP ligases only. Comparative genomics of loci containing these enzymes revealed that they can be independently recruited as tailoring genes in diverse secondary metabolite pathways. Based on these results, we propose a refined and clear phylogeny-based classification of A domain-containing enzymes, which will provide a robust framework for future functional analyses and engineering of these enzymes to produce new bioactive molecules.

A novel methodology for optimal location of reactive compensation through deep neural networks.

The present investigation proposes a methodology for the optimal location of reactive compensation in an electrical power system (EPS) through deep neural networks for voltage profile improvement. One of the main parameters to consider regarding EPS reliability is the voltage profile, a parameter that can be affected due to unexpected increases in impedance and loads in the system that translate as overloads in the system and an increase in the number of users. A voltage profile below the minimum or above the maximum accepted in the regulations of each country puts at risk the correct operation of equipment connected to the electrical network and, in turn, can cause economic losses and human lives (e.g by not guaranteeing reliability for hospitals and similar institutions). Economically, one of the most viable alternatives for improving voltage profiles is reactive compensation which in itself is carried out through capacitor banks. Therefore, this work proposes to find the correct location of capacitor banks in an electrical power system (using IEEE 14, 30 and 118 bus-bars systems as cases of study). In each system, the highest reactive load is identified, thus three values for reactive compensation are established as 80%, 50% and 25% of this maximum. Then, with these values, power flows are generated by locating each one of the reactive compensators' possible values in each one of the bars of the system, hence generating a large number of training data so that finally the neural network is capable of providing a quantitative classification highlighting which compensation and in which bus-bar produces the best result. The result is assessed by applying a modified standard deviation which evaluates the separation of the voltage profiles from the ideal desired value of 1pu.

Metanephric adenoma: differential diagnosis of upper tract urothelial carcinoma. a case report

ABSTRACT Introduction: Metanephric adenoma is a rare benign kidney tumor. Patients with these tumors are usually asymptomatic, although polycythemia occurs in up 12% of cases. These masses are often described on diagnostic imaging as solid, single, well-defined, oval-shaped, unilateral lesions, located primarily in the renal medulla and without extrarenal involvement. These neoplasms are difficult to differentiate from malignant neoplasms of the upper urinary tract, so the definitive diagnosis is achieved by histopathology. Currently, the treatment of choice is radical nephrectomy. Case presentation: A 51-year-old woman from Bogotá (Colombia) was referred to the urology service of a tertiary care hospital due to bilateral lumbar pain of non-specific characteristics. At the time of consultation, the patient was asymptomatic. Renal and urinary tract ultrasound showed hydronephrosis and right renal mass. Computed tomography urography was requested, which revealed a lesion in the right renal pelvis with parenchymal invasion highly suggestive of high-risk upper urinary tract urothelial carcinoma, as well as adenopathies in the para-aortic lymph nodes. The patient underwent a radical nephroureterectomy with bladder cuff, which allowed establishing a final diagnosis of metanephric adenoma according to the histopathological study. Conclusions: Metanephric adenoma is a rare tumor that is difficult to diagnose through imaging, so it is necessary to explore additional tools to establish an accurate pre-surgical diagnosis that allows preserving the affected renal unit. Also, given their non-specificity, these tumors should be included in the differential diagnosis of lesions suggestive of upper tract urothelial carcinoma.

RESUMEN Introducción. El adenoma metanéfrico es un tumor renal benigno poco frecuente. Los pacientes con estos tumores no suelen presentar síntomas, aunque en el 12% de los casos se presenta policitemia. En las imágenes diagnósticas, los adenomas metanéfricos se observan como lesiones sólidas, únicas y bien definidas que, por lo general, comprometen la medula renal pero no ocasionan compromiso extrarenal. Estas neoplasias son difíciles de diferenciar imagenológicamente de neoplasias malignas del tracto urinario superior, por lo que el diagnóstico definitivo se logra mediante estudios histopatológicos. El tratamiento de elección es la nefrectomía radical. Presentación del caso. Mujer de 51 años procedente de Bogotá (Colombia), quien fue remitida al servicio de urología de un hospital de tercer nivel de atención por dolor lumbar bilateral de características inespecíficas. Al momento de la consulta la paciente se encontraba asintomática. Mediante ecografía renal y de vías urinarias se evidenció hidronefrosis y una masa renal derecha. Se ordenó urografía por tomografía axial computarizada que documentó una lesión en la pelvis renal derecha con invasión al parénquima renal altamente sugestiva de carcinoma urotelial de tracto urinario superior de alto riesgo, así como adenopatías en los ganglios paraaórticos, por lo que se le realizó una nefroureterectomía radical derecha con cuña vesical que permitió establecer un diagnóstico final de adenoma metanéfrico según el estudio histopatoló-gico. La paciente tuvo una evolución satisfactoria. Conclusiones. El adenoma metanéfrico es un tumor poco frecuente y de difícil diagnóstico imagenológico, por lo que se requiere explorar herramientas adicionales para establecer un diagnóstico certero prequirúrgico que permita preservar la unidad renal afectada. Asimismo, dada su inespecificidad, estos tumores deben incluirse dentro de los diagnósticos diferenciales de las lesiones sugestivas de carcinoma urotelial de tracto urinario superior.