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Resumen Introduccion Los datos disponibles de las causas de muerte en pacientes ingresados por insuficiencia cardiaca en servicios de medicina interna y en poblacion espanola segun fraccion de eyeccion reducida (FER), preservada (FEP) e intermedia (FEI) son escasos. Su estudio puede mejorar el conocimiento de estos pacientes y su pronostico. Metodos Estudio de cohortes multicentrico y prospectivo de 4.144 pacientes que ingresaron por insuficiencia cardiaca en unidades de medicina interna. Se registraron sus caracteristicas clinicas, tasa de fallecimientos y sus causas agrupadas segun FEP (≥ 50%), FEI (40-49%) y FER ( Resultados Se registraron 1.198 fallecimientos (29%), de los que 833 fallecieron por causas cardiovasculares (69,5%), fundamentalmente por insuficiencia cardiaca (50%) y por muerte subita (7,5%) y 365 por causas no cardiovasculares (NoCV) (30,5%), sobre todo por infecciones (13%). La causa mas frecuente y temprana en todos los grupos fue la insuficiencia cardiaca. Los pacientes con FEP tenian menor tasa de muerte subita y mayor de infecciones (p Conclusiones Las causas de muerte en pacientes con insuficiencia cardiaca fueron diferentes dependiendo del tipo de fraccion de eyeccion. Los pacientes con FEI y FEP, por su elevada comorbilidad y mayor frecuencia de muerte NoCV, son los que mas se beneficiarian de un manejo integral por parte de medicina interna.

Introduction and objectives We present a clinical case of a 40-year-old woman diagnosed with acute myocardial infarction (AMI) in Killip I who was admitted to our hospital. She experienced complications in the haemodynamic lab and in the operating room, including cardiogenic and anaphylactic shock requiring ventricular assist support. Conservative management support with inotropes and vasopressors in cardiogenic shock has been shown to be insufficient in many patients to maintain adequate perfusion and prevent irreversible multiple organ dysfunction syndrome. For this reason, short-term mechanical circulatory support systems are increasing substantially. The objective of this article is to develop optimal and individualised care plans using the NANDA, NOC, NIC taxonomies. Clinical observation An evaluation based on Virginia Henderson’s basic needs was made, and two altered needs stood out: breathing and circulation. The patient required mechanical ventilation and mechanical circulatory support. Interventions In relation to the highlighted needs, six diagnoses were prioritized according to the NANDA taxonomy using the Analisis de Resultado del Estado Actual (AREA) (Outcome-Present State Test (OPT)) model: risk of decreased cardiac output, impaired spontaneous ventilation, impaired tissue integrity, risk of disuse syndrome, risk of infection and risk of hypothermia. Discussion and conclusions Outcome criteria scores showed a favourable evolution after 96 h. The development of a standardized NANDA-NOC-NIC language allowed us to organize the nursing care plan.

Background Fluoroscopic‐guided lumbar procedures have increased in daily pain practice because the lumbar spine is one of the most common sources of pain. Interventional pain fellows must develop a minimum number of skills during their training in order to achieve the competences without neglecting radiological safety. However, medical training in fluoroscopic‐guided interventions is being affected by the current coronavirus disease 2019 (COVID‐19) situation. Methods The objective of this study was to evaluate the use of a phantom model for lumbar injection as a training strategy during the COVID‐19 pandemic in fellows of interventional pain. The study was divided into theoretical and practical modules. The hands‐on practice was performed in a lumbar model phantom where fellows were evaluated in four fluoroscopically guided approaches: intra‐articular facet block (IAFB), medial branch block (MBB), transforaminal block (TFB), and interlaminar block (ILB) divided in 5 sessions. The aim was to make as many punctures as possible in every session. We measured total procedural performance (TPP), total needle hand time (TNH), and total radiation dose generated by the fluoroscopic machine (TRD) during each procedure. Additionally, a survey was applied to evaluate confidence and satisfaction before and after training. Results A total of 320 lumbar punctures were completed. The results were statistically significant in all approaches attempted (p

In this work, the performance of a semicircular cylinder with the flat side parallel to the incoming flow has been studied experimentally in a wind-excited energy harvester. Preliminary sectional model wind tunnel tests have allowed the identification of the reduced velocity ranges howing appreciable wind-induced oscillations. Interestingly, vortex-induced vibration-galloping interferences have been identified for both heave and pitch degrees of freedom at low reduced wind speeds, as well as coupled galloping in the higher ranges of flow velocities. The impact on the aeroelastic response caused by the attachment of a small-diameter rod at different positions has been studied, finding an enhancement in the amplitude of the oscillations and an enlargement in the vortex-induced vibration excitation range for some of them. Based on these preliminary results, an energy harvester has been designed adopting a cantilever beam supporting the semicircular cylinder. The device has showed a good performance reaching 2.5 mW of averaged harvested power for the configuration with a small-diameter rod attached at γ=85º for 8 m/s flow speed.

Pharyngitis and tonsillitis are the most common acute respiratory infections (ARIs) in children aged ≤5 years. The analysis of published data showed that some probiotics could decrease the frequency and number of days with ARIs. This study evaluated the safety and efficacy of Limosilactobacillus reuteri ATCC PTA 5289 and DSM 17938 to reduce the duration and severity of ARI symptoms. This randomised controlled trial included children aged from 6 months to 5 years, with pharyngitis or tonsillitis, who were randomised to receive a probiotic product containing L. reuteri ATCC PTA 5289 and L. reuteri DSM 17938 or placebo, as drops, ingested orally for 10 days as adjuvants to the use of non-steroidal anti-inflammatory drugs. The main outcomes were the duration and severity of ARI symptoms. The secondary outcomes were changes in salivary immunoglobulin A and inflammatory biomarkers. There was no fever on day 2 and subsequent days in the L. reuteri group (37.3 ±0.5 °C vs 38.6±0.3 °C, P

Introducción: En México, las úlceras por presión (UPP) son un indicador de calidad en el Sistema Nacional de Salud, se otorga relevancia a los conocimientos de los profesionales de la salud en cuanto al abordaje integral de las úlceras para el mejoramiento de la seguridad del paciente. Objetivo: Evaluar la efectividad de una intervención educativa como herramienta para mejorar los conocimientos de enfermería en la prevención y tratamiento de las UPP. Método: Estudio pre-experimental basado en una intervención educativa aplicada a un grupo con medición pre y post. La muestra estuvo constituida por 90 licenciados de enfermería que laboran en hospitales públicos de segundo y tercer nivel de atención, ubicados en el puerto de Veracruz. Se diseñaron doce sesiones de 120 minutos cada una para la intervención; en estas se abordaron tópicos de prevención, cuidado y tratamiento de las úlceras. Resultados: La variable prevención, en el indicador adecuado según tus conocimientos, obtuvo un promedio inicial de 74±15 que incrementó en la segunda medición a 91±9. t (p=.003). En la variable tratamiento, el indicador adecuado según tus conocimientos, obtuvo un promedio inicial de 57±16 y en la segunda medición pasó a 76±9. t (p=.002). Conclusión: La aplicación de la intervención educativa permitió mejorar el conocimiento sobre prevención y tratamiento de las UPP, aunque la utilización en la práctica asistencial fue menor.

Introduction Clinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety. Methods We summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12. Results Across the studies, evolocumab reduced LDL-C by a mean 55–61% from baseline to week 12; ezetimibe lowered LDL-C by 18–20% from baseline (mean difference = 38–43% favoring evolocumab; p, Plain language summary A statin is a type of medication that is used, with diet and exercise, to lower cholesterol levels and help prevent a heart attack or stroke caused by atherosclerosis. Atherosclerosis is the hardening and narrowing of blood vessels known as arteries from a buildup of plaque, usually made up of cholesterol and other fatty substances. LDL cholesterol, also known as “bad” cholesterol, is one of the most important risk factors for having a heart attack, and can be lowered. Patients with a high risk of heart disease may benefit from the additional lowering of LDL cholesterol beyond that achieved by statins alone. The medication evolocumab reduced LDL cholesterol levels and improved other risk factors more than the medication ezetimibe in four studies. These studies included patients who were receiving statins and those who were not, including those who did not receive statins because of statin-related side effects. Both evolocumab and ezetimibe had good safety profiles.

Resumen Antecedentes y objetivos La heterogeneidad de los pacientes con insuficiencia cardiaca y fraccion de eyeccion preservada (ICFEP) es elevada, por lo que se tiende a agrupar en fenotipos para intervenir con precision. Dentro de estos, los pacientes con diabetes mellitus (DM) mantienen esta heterogeneidad. Nuestro objetivo es describir grupos de pacientes con ICFEP y DM basados en otras comorbilidades. Material y metodos Los pacientes se reclutan desde el registro nacional de insuficiencia cardiaca (RICA). Se incluyen pacientes con fraccion de eyeccion mayor o igual al 50% sin valvulopatia y con DM. Se realiza un analisis aglomerativo jerarquico con el metodo de Ward incluyendo las siguientes variables: dislipemia, hepatopatia, EPOC, demencia, enfermedad cerebrovascular, arritmia, presion arterial sistolica, indice de masa corporal (IMC), estimacion del filtrado glomerular y hemoglobina. Resultados Se incluyen 1.934 pacientes con ICFEP, de los que 907 (46,9%) tenian DM, con predominio de mujeres (60,9%) y con un IMC de 31,1 (5,9) kg/m2. Se obtienen 4 grupos: dos con elevado riesgo vascular (uno con arritmia y otro no), con 263 pacientes el primero y 201 el segundo, otro con predominio de EPOC (140 pacientes) y un ultimo grupo de 303 pacientes con mas edad pero menos comorbilidad. Conclusiones En nuestros pacientes con ICFEP y DM predomina la obesidad y el sexo femenino. Los cuatro grupos ofrecen oportunidades de tratamiento para mejorar su pronostico no solo basadas en la utilizacion de nuevos farmacos antidiabeticos sino por otras opciones que pueden suponer un punto de partida para nuevas investigaciones.

Background People living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and prone to statin-related adverse events from drug-drug interactions with certain antiretroviral regimens. Objectives This study sought to evaluate the efficacy and safety of evolocumab in dyslipidemic PLHIV. Methods BEIJERINCK is a randomized, double-blind, multinational trial comparing monthly subcutaneous evolocumab 420 mg with placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia taking maximally-tolerated statin therapy. The primary endpoint was the percent change (baseline to week 24) in low-density lipoprotein cholesterol (LDL-C); secondary endpoints included achievement of LDL-C Results A total of 464 patients were analyzed (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). ASCVD was documented in 35.6% of patients, and statin intolerance/contraindications to statin use were present in 20.7% of patients. Evolocumab reduced LDL-C by 56.9% (95% CI: 61.6%, 52.3%) from baseline to week 24 versus placebo. An LDL-C level of Conclusions Evolocumab was safe and significantly reduced lipid levels in dyslipidemic PLHIV on maximally-tolerated statin therapy. Evolocumab is an effective therapy for lowering atherogenic lipoproteins in PLHIV with high cardiovascular risk.

Aortic dissection (AD) is the most common acute condition of the aorta and has a high mortality. Therefore, it is a radiological emergency of vital importance. Currently, five subtypes are distinguished, among which AD class 3 – also known as limited or subtle AD- is the less recognised. This type of dissection is infrequent and needs to be acknowledged radiologically in order not to go unnoticed. Regarding its imaging features, this entity is characterized by a small focal bulging of the aortic wall outline and/or a limited round dilation at the region affected by the intimal tear. Recently, the low familiarity of the radiologist with this condition has been emphasized. With the aim of illustrating the main imaging findings of this entity and reviewing its most relevant aspects, we present four cases of AD class 3 diagnosed in our hospital.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR)= 1.02 (0.66-1.58), two-sided P= 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR= 0.95 (0.59-1.52), P= 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade =3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Introduction/Background* The goal of this study is to review the sentinel lymph node (SLN) in endometrial cancer in the University Hospital 12 de Octubre in Madrid from June 2016 to October 2020. The aim is to know the demographic and clinical features of the patients and to assess the outcomes of SLN in our population with technetium99 (Tc99), indocyanine green (ICG) or blue dye. Methodology Result(s)* From June 2016 to October 2020, 166 patients diagnosed with endometrial cancer underwent surgery in our hospital. In 34.4% (n= 57) of them SLN was performed and included in this review. Demographic and clinical features are shown in table 1. 80.7% (n=46) were classified as low risk endometrial cancer and 19,3% (n=11) as intermediate risk. Laparoscopy was the most frequent approach (96.4%). Median operative time was 203 minutes (IQR, 173 to 249). A combined tracer technique was used in 75.4% cases. Most of them combining Tc99 and ICG (64.9%). Tc99 and blue dye were used in 10.5%. Only one tracer was used in 24.6% (Tc99 5.3%; ICG 17.5%; blue dye 1.8%). Cervix was the only injection site into submucosa and stroma. In 89.5% of the patients, tracer migration was observed. Only 6 patients (10.5%) had no migration. In table 2, detection and migration data of the tracers are shown. One hundred forty-four SLNs were detected. Right side (52.8%) was slightly more frequent than left side (47.2%). Most SLNs were located in external iliac area (40.5%), followed by iliac bifurcation (25.3%), obturator fossa (17.7%) and common iliac (13.9%). In three patients isolated tumor cells were detected (5.2%) and one patient had macrometastases (1.8%). 93% of the patients had no pathological findings in SLNs. Age was significantly higher in the no migration/no detection group in both Tc99 (70 vs 58.5 years; p= 0.01) and ICG/blue dye (72.5 vs 59.4 years; p=0.034). No migration/detection differences were detected for other patient´s features. Conclusion* A combined tracer technique is an effective method to detect SLNs in low-risk endometrial cancer to check lymphatic spread. Older women in our series have lower tracer migration/detection.

Introduction/Background* Women with germline mutations in the BRCA ½ genes have a lifetime increased risk of ovarian cancer, 36 - 63% and 10-27% respectively. Accordingly, once childbearing is completed, Risk Reduction Salpingo-oophorectomy (RRSO) is recommended in this group of patients. The purpose of this study was to determine the presurgical findings and the incidence of Serous Tubal intraepithelial carcinoma (STIC) and occult carcinomas in BRCA mutations carriers in whom a RRSO was performed. Methodology Prospective study that included patients with documented BRCA mutation who accepted RRSO between January 2011 to January 2021 at the Hospital Universitario 12 de Octubre. The study was approved by the ethics committee of the institution. During the month prior to surgery, a systematic ultrasound (US) and determination of serum Ca 125 levels were performed. Specialized gynecologists performed RRSO by laparoscopy. Unilateral or bilateral adnexectomy was performed according to the surgical history of each patient. Pelvic washing was done in all cases at the beginning of the procedure and tubes were removed at the uterine insertion. All the histologic exams were performed by pathologists subspecialized in Gynecologic Oncology and the sectioning and extensively examining of the fimbriated end protocol (SEE-FIM protocol) was applied. STIC was defined using a combination of morphologic evaluations to distinguish in from p53 signatures, STIL and invasive carcinoma. All statistical analysis was performed by Stata/IC 13.0 for Windows. Result(s)* A total of 115 were included. Of them, 50.4% had BRCA 1 mutation and 49.6% BRCA 2 mutation. Mean (+/- Standard deviation, SD) age at surgery was 49.2 (5.8) years. Of note, 40.9% underwent surgical menopause. The median Ca-125 value prior to surgery was 29.4 u/L. Adnexal findings in presurgery ultrasound were normal (104, 90.4%) or benign cyst (11, 17.4%). Also, endometrial polyps were found in 3.5% (3) of patients. Pathologic exam showed STIC in 5 (4.5%) patients and invasive ovarian carcinoma in 1 (0.9%). Conclusion* Currently, RRSO is the only tool to reduce the risk of ovarian cancer in BRCA mutations carriers. However, the incidence of STIC after RRSO is not very high.

Introduction/Background* Management of endometrial cancer (EC) in pre-menopausal women represents nowadays a clinical challenge. The median age of diagnosis of EC is 65 years. Prevalence has increased in the last years in younger people related to increased risk factors. Around 20% of cases are diagnosed before menopause. EC typically presents with abnormal uterine bleeding. The diagnostic evaluation of pre-menopausal patients with this main clinical feature supposes an additional difficulty. The aim of our study is to evaluate the clinical and pathologic factors associated with EC in this group. Methodology Retrospective unicentric study of 244 patients with EC diagnosed, treated and followed-up at Hospital Universitario 12 de Octubre (Madrid, Spain) between 2013 and 2020. Exclusion criteria were neoadjuvant chemotherapy or primary radiation as treatment. Menopausal status at diagnosis was used to classify patients into two groups. Result(s)* A total of 244 patients were included, of which 45 (18.4%) were pre-menopausal and 199 (81.6%) were postmenopausal. Demographic and pathologic characteristics of the two cohorts are described in table 1. Conclusion* In our institution, premenopausal status was associated with a lower parity record (1.1±0.8 vs 2.15±1.3, p=0.04), lower prevalence of hypertension (13.0% vs 59.4%, p=0.001), higher rate of smokers (28.9% vs 14.9%, p=0.039) and endometrioid histology (97.8% vs 83.5%, p=0.01). Hysterectomy was performed in all cases, and only one premenopausal patient underwent ovarian preservation. A total of 39.1% and 38.0% of the patients had pelvic lymph node assessment in the premenopausal and postmenopausal groups, respectively (p=0.4) and paraaortic in 37.0% and 30.0% (p=0.19). There was no significant difference in stage distribution, grade differentiation, myometrial invasion or lymphovascular space invasion, between the two groups. The rate of administration of adjuvant chemotherapy was 15.6% in premenopausal and 13.8% in postmenopausal patients (p=0.75) and 28.9% and 37.9% (p=0.26) of adjuvant radiotherapy, respectively. According to these results, in our population, there was no significant difference in the favourable clinical prognostic factors in premenopausal women. The retrospective nature of the study and the small size of the cohort could justify these findings.

Agave bagasse is a fibrous-like material obtained during aguamiel extraction, which is also in contact with indigenous microbiota of agave plant during aguamiel fermentation. This plant is a well-known carrier of the prebiotic fructan-type carbohydrates, which have multiple ascribable health benefits. In the present work, the potential of ashen and green agave bagasse as functional ingredients in supplemented cookies was studied. For its application, the chemical, functional, properties of agave bagasses and formulated cookies were evaluated, as well as the physical properties of cookies. Chemical characterization was carried out by the proximate analysis of both bagasses and cookies, besides, the analysis of oligosaccharides was made by thin-layer chromatography and high-performance anion-exchange chromatography. In the same way, functional properties such as oil holding capacity, organic molecule absorption capacity, swelling capacity, and water holding capacity were analyzed in both agave bagasses and supplemented cookies. Finally, modifications in color and texture due to bagasse addition was studied through an analysis of total color difference and a penetrometric test, respectively. In this sense, ashen and green agave bagasses demonstrated chemical and functional properties for use in the food industry, since they increased oil holding capacity of cookies and transferred prebiotic fructooligosaccharides to both agave bagasse formulations, which remain active as a prebiotic ingredient in cookies after in vitro digestion and cookie manufacture, including thermal treatment. Hence, agave bagasse could be considered a valuable alternative for the addition of the nutritionally-relevant dietary fiber in healthier foods.

The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized phospholipid (OxPL) apoB levels were measured using validated methods. Median Lp(a) concentrations among participants with and without PCSK9 LOFVs were 63.2 and 80.4 nmol/l, respectively (P = 0.016). After adjusting for age, sex, estimated glomerular filtration rate, LDL cholesterol, and statin use, participants with versus without a PCSK9 LOFV had a lower median Lp(a) concentration [Δ = -18.8 nmol/l (95% CI: -34.2, -3.3)]. Median apo(a) isoform sizes were 24 and 23 KIV repeats (P = 0.12) among participants with and without PCSK9 LOFVs, respectively [Δ = 1.1 (95% CI: 0.2, 2.0) after adjustment]. Median OxPL-apoB levels among participants with and without PCSK9 LOFVs were 3.4 and 4.1 nM (P = 0.20), respectively [Δ = -1.2 nM (95% CI -2.4, -0.04) after adjustment]. Among black adults, PCSK9 LOFVs were associated with lower Lp(a) concentration and OxPL-apoB levels.

Terpenes are naturally produced compounds with a broad range of biological activities. Currently, there is limited information regarding the anthelminthic effect of terpenes against monogenean parasites of fish. The aim of this work was to evaluate the in vitro efficacy of two terpenes [α-terpinene and (+)-limonene oxide] against ancyrocephalid monogeneans found on farmed Nile tilapia (Oreochromis niloticus). (+)-Limonene oxide was more effective in killing these parasites than α-terpinene, with 86 and 90% mortality at concentrations of 36 and 55.4 mg/L, respectively, with a 5-h treatment. The estimated 5-h EC(50) of (+)-limonene oxide was 4.8 mg/L. Even though this compound has the potential to be used as an anthelmintic compound in finfish aquaculture, before in vivo experiments are performed, additional studies are needed to find a more effective concentration, as well as to evaluate other terpenic compounds.

Background : Chronic kidney disease (CKD) is a growing public health concern, and available treatments are insufficient in limiting disease progression. New strategies, including regenerative cell-based therapies, have emerged as therapeutic alternatives. Results : from several groups, including our own, have reported evidence of a supportive role for mesenchymal stromal cells (MSCs) in functional recovery and prevention of tissue damage in murine models of CKD. Prompted by these data, an open pilot study was conducted to assess the safety and efficacy of a single injection of autologous adipose tissue-derived MSCs (AT-MSCs) for treatment of CKD. Methods : AT-MSCs were infused intravenously into six CKD patients at a dose of 1 million cells/kg. Patients were stabilized and followed for one year prior to MSC infusion and one year following infusion. Results : No patients presented with adverse effects. Statistically significant improvement in urinary protein excretion was observed in AT-MSCs transplanted patients, from a median of 0.75 g/day (range, 0.15-9.57) at baseline to 0.54 g/day (range, 0.01v2.66) at month 12 (P = 0.046). The glomerular filtration rate was not significantly decreased post-infusion of AT-MSCs. Conclusion : Findings from this pilot study demonstrate that intravenous infusion of autologous expanded AT-MSCs into CKD patients was not associated with adverse effects and could benefit patients already undergoing standard medical treatment.

A fundamental model of tumor growth in the presence of cytotoxic chemotherapeutic agents is formulated. The model allows to study the role of the Norton-Simon hypothesis in the context of dose-dense chemotherapy. Dose-dense protocols aim at reducing the period between courses of chemotherapy from three weeks to two weeks, in order to avoid tumor regrowth between cycles. We address the conditions under which these protocols might be more or less beneficial in comparison to less dense settings, depending on the sensitivity of the tumor cells to the cytotoxic drugs. The effects of varying other parameters of the protocol, as for example the duration of each continuous drug infusion, are also inspected. We believe that the present model might serve as a foundation for the development of more sophisticated models for cancer chemotherapy.

Introduction The apolipoprotein A1 (apoA1) remnant ratio has been identified as an independent cardiovascular (CV) risk factor. Higher apoA1 remnant ratios may predict lower CV risk in some patients. This analysis aimed to evaluate the effects of evolocumab on the change from baseline in the apoA1 remnant ratio compared with placebo. Methods This pooled post hoc analysis included 2464 patients with mixed dyslipidemia treated with evolocumab 140 mg every 2 weeks (Q2W) or 420 mg once monthly (QM) in three phase 3 evolocumab trials. The apoA1 remnant ratio was calculated by dividing apoA1 by the difference between non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C). ApoA1 remnant ratio strata were generated using previously published tertile ( 6.8) and partitioning categories ( 6.0). Results The baseline apoA1 remnant ratio in evolocumab and placebo treatment arms was 7.1 and 7.3, respectively. At week 12, evolocumab 140 mg Q2W and 420 mg QM increased the apoA1 remnant ratio by 25.0% and 33.6%, respectively, versus placebo (p 3.6, and 4.7), those with higher week 12 apoA1 remnant ratios were significantly more likely to have also achieved a target non-HDL-C level of 50 years of age, the proportion of patients at apoA1 remnant ratio thresholds 6.0 at baseline shifted toward or remained at higher thresholds at week 12. Conclusions This post hoc analysis suggests that evolocumab increases the apoA1 remnant ratio. Funding Amgen Inc. Plain Language Summary Plain language summary available for this article. Electronic supplementary material The online version of this article (10.1007/s40119-019-0133-6) contains supplementary material, which is available to authorized users.

Introduction Regenerative endodontic procedures have emerged as a new treatment. The aim of this case report was to describe a regenerative autologous cellular therapy using mesenchymal stem cells from inflamed dental pulp and leukocyte platelet-rich fibrin (L-PRF) in a mature tooth. Methods A healthy 50-year-old man consulting for spontaneous dental pain was referred for endodontic treatment in tooth #28, which was diagnosed with symptomatic irreversible pulpitis. Inflamed dental pulp was extracted and transported to a good manufacturing practice laboratory for the isolation and culture of dental pulp stem cells (DPSCs). L-PRF was obtained from the patient's blood and was introduced into the instrumented and disinfected root canal, and expanded DPSCs were inoculated into the clot. The cervical part of the root canal was sealed with Biodentine (Septodont, Saint-Maur-des-Fosses, France) and a composite resin. Results Follow-up examinations were performed 6 months and 3 years later. The examinations included periapical radiographs (to measure the periapical index [PAI]), cone-beam computed tomographic (CBCT) imaging, sensitivity, and vitality tests. Clinical evaluations revealed normal responses to percussion and palpation tests. The tooth had a delayed response to cold, and the electric pulp test was responsive. The PAI and CBCT imaging revealed that the periapical area remained normal with a PAI score of 1 and a CBCT PAI score of 0. The vitality test performed indicated low blood perfusion units. Conclusions This case study reveals the potential use of a patient's own DPSCs and L-PRF as an alternative procedure for the treatment of pulpitis in mature permanent teeth. It also paves the way for the design of personalized cell-based clinical trials in regenerative endodontics.

Introduction and objectives Acute heart failure (AHF), can occur as decompensated chronic heart failure (HF) or as a first episode, “new onset”. The aim of this study was to analyse the clinical characteristics and prognosis at one-year in a cohort of patients with new onset AHF. Methods Prospective observational study of 3550 patients with AHF. We compared patients with new onset HF with the others. Restricting the analysis to new onset AHF patients, we analysed the clinical characteristics, readmissions, mortality and impact of left ventricular ejection fraction on the prognosis. Results A total of 1105 (31%) patients fulfil the criteria for new onset AHF. These patients versus the rest, were younger, had a higher aetiology of hypertension and preserved left ventricular ejection fraction, less global comorbidity and better baseline overall functional status. After one year, mortality in new onset HF was less than chronic decompensated HF (15 vs. 27%; p Conclusions New onset AHF shows a clinical profile and prognosis different to that of chronic decompensated HF. Higher comorbidity, renal function and treatment post-discharge predict a higher risk of mortality.

Resumen Introduccion y objetivos La insuficiencia cardiaca aguda (ICA) puede suceder como una descompensacion de una IC cronica o como un primer episodio “de novo”. Nuestro objetivo fue analizar las caracteristicas clinicas y el pronostico al ano, en una cohorte de ICA de novo. Metodos Estudio observacional y prospectivo de 3550 pacientes con ICA. Se analizan las caracteristicas clinicas, la fraccion de eyeccion ventricular izquierda, los reingresos y factores asociados a mayor mortalidad al ano de los pacientes con ICA de novo y se comparan con el resto. Resultados Un total de 1105 (31%) pacientes, presentaron ICA de novo. Este grupo fue mas joven, con mayor etiologia hipertensiva y fraccion de eyeccion ventricular izquierda preservada, mejor estado funcional y menor comorbilidad que el resto de la cohorte. Al ano de seguimiento, la mortalidad fue menor en ICA de novo frente a IC cronica descompensada (el 15 vs. el 27%; p Conclusiones Los pacientes con ICA de novo tienen un perfil clinico diferente a la IC cronica descompensada, con un mejor pronostico. Los principales factores predictores de mortalidad al ano en ICA de novo fueron la comorbilidad global, la funcion renal y el tipo de tratamiento al alta hospitalaria.

Objective Several studies have reported that a higher degree of hemoconcentration in patients admitted for the treatment of acute heart failure (HF) constitutes a favorable prognostic factor in the year following the index episode. The objective of this study was to evaluate whether the highest degree of hemoconcentration at 3 months after admission for HF is also a prognostic factor for mortality and/or readmission in the 12 months after admission. Patients and method The hemoconcentration group was the upper quartile of the sample distributed according to hemoglobin increase at month 3 after discharge with respect to hemoglobin at the time of admission for HF in a multicenter prospective cohort of 1659 subjects with HF. Results The mean follow-up until the first event was 294 days, and a total of 487 deaths and 1125 readmissions were recorded. The hemoconcentration group had a lower risk of mortality or readmission for any cause (RR = 0.75, 95% CI: 0.51–1.09 and RR = 0.86, 95% CI: 0.70–1.05), although statistical significance was lost after multivariate analysis, while it was retained for other factors with recognized negative impact on the prognosis of patients with HF, such as age and functional class. Conclusions The degree of hemoconcentration at 3 months after admission for HF is not prognostic of readmission or death in the subsequent year.

We present a case of multiple lymphangiohemangiomas (hematolymphangiomas, hemangiolymphangiomas, or combined lymphatic venous malformation) with thoracic and abdominal involvement in an asymptomatic patient. We describe and illustrate the imaging findings in this disease, which are quite characteristic and can enable an accurate diagnosis. To our knowledge, there are no other reports of similar cases in the scientific literature.

Resumen Objetivo Diferentes estudios senalan que la consecucion de una mayor hemoconcentracion en pacientes ingresados por insuficiencia cardiaca (IC) aguda mejora el pronostico a lo largo del ano siguiente al episodio indice. El objetivo de este estudio es evaluar si el grado de hemoconcentracion a los 3 meses tras el ingreso por IC tambien tiene valor pronostico de reingreso y/o mortalidad en los 12 meses siguientes al ingreso. Pacientes y metodo Cohorte prospectiva multicentrica de 1.659 pacientes con IC. El grupo hemoconcentracion (305 pacientes) se situo en el cuartil superior de la muestra distribuida en funcion del aumento de la hemoglobina en el mes 3 tras el alta con respecto a la hemoglobina en el ingreso por IC. Resultados Seguimiento medio hasta el primer evento fue de 294 dias, fallecieron 487 pacientes y reingresaron 1.125. El grupo hemoconcentracion mostro un riesgo menor de mortalidad o de reingreso por cualquier causa (RR = 0,75; IC 95%: 0,51-1,09 y RR = 0,86; IC 95%: 0,70-1,05), si bien la significacion estadistica se perdio tras el analisis multivariado. Sin embargo, esta significacion se mantuvo para otros factores con reconocido efecto negativo sobre el pronostico en pacientes con IC, como son la edad y la clase funcional. Conclusiones El grado de hemoconcentracion a los 3 meses tras el ingreso por IC no tiene valor pronostico de reingreso o muerte en el ano siguiente.

Dear Editor The sympathetic innervation of the abdominal viscera is formed from the ventral branches of levels T5–T12. From these branches, the greater, lesser and least splanchnic nerves are formed, to finally synapse at the coeliac plexus. These branches innervate the distal oesophagus, transverse colon, pancreas, liver, adrenal glands and ureters and regulate the abdominal blood supply.1 This explains the efficacy of splanchnic nerve block in patients with upper abdomen and lower oesophageal neoplasms. Plancarte et al reported a significant improvement in pain levels and reduction of painkillers intake in 109 patients with upper abdomen and lower oesophageal neoplasms, administering 8–10 mL of 10% phenol in the retrocrural and retroaortic space, using a single-needle, posterior transdiscal approach, guided by CT scan.2 Over time, several techniques for splanchnic nerve block have been described, either guided by CT scan or fluoroscopy, administering volumes even greater than 10 mL …

Background Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM. Methods This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD. Results In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C 75% achieved non-HDL-C 67% achieved ApoB Conclusions Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.

Funding Acknowledgements Type of funding sources: None. Background Venous to arterial CO2 gap (CO2gap) is calculated by subtracting partial pressure of arterial CO2 to central venous partial pressure of CO2 (ScvCO2). This marker has been studied in septic shock and indicates hypoperfusion when exceeds 6mmHg. Its kinetics and applicability in cardiogenic shock (CS) are unclear, being mixed/central venous saturation and lactate more commonly used. Purpose The objective of the study is to describe CO2gap kinetics in patients with CS. Secondary objective is to analyze if CO2gap is as marker of prognosis in CS. Methods Prospective observational study that included patients admitted for CS in the Acute Cardiovascular Care Unit of a tertiary hospital. Gasometric samples were obtained at admission, 6, 12, 24 and 48 hours from the onset of shock. In-hospital mortality was registered. Results We included 40 patients with CS during 1 year. Most patients were male (80%), average age was 68 years. There was a high incidence of cardiac arrest (58%), most frequent cause of CS was STEMI (45%), in-hospital mortality was 45%, most cases from non-cardiovascular causes (61%). Refractory shock was frequent (28%). Average lactate peak was 6.02 mmol / L. CO2gap kinetics consisted in a peak at admission (8.8mmHg), a valley 6h (7.7mmHg), new peak at 12h (8.5mmHg) and progressive decrease at at 24 (6.8mmHg) and 48h (5.7 mmHg). Significantly, higher CO2gap values at admission (10.97mmHg vs 8.16mmHg, p = 0.007) was predictor of cardiovascular mortality. Lactate values at 6, 12 and 48 hours were also predictors of cardiovascular mortality, as well as ScvO2 at admission. Conclusions Patients with CS present with high CO2gap values during first hours of admission. The kinetics of this marker consists in two peaks at admission and 12 hours from CS onset, a valley at 6 hours and a progressive decrease at 24 and 48 hours. Its determination at admission is associated with cardiovascular mortality. We suggest the potential benefit of combining this marker, along with lactate and ScvO2 values, to guide management of patients with CS. Abstract Figure. CO2 gap and cardiovascular mortality

We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are im-plicated in the “Cholinergic anti-inflammatory pathway”, we aimed to determine how α7 nAChR stimulation modulates microglial phenotype in an LPS-induced neuroinflammation model in adult and aged mice. For this, BALB/c mice were injected intraperitoneally with LPS (0.33 mg/kg) and treated with the α7 nAChR agonist PNU282987, using different administration protocols. LPS challenge reduced body weight and induced lethargy and social withdrawal in adult mice. Peripheral (intraperitoneal) co-administration of the α7 nAChR agonist PNU282987 with LPS, attenuated body weight loss and sickness behavior associated with LPS challenge in adult mice, and reduced microglial activation with suppression of IL-1β and TNFα mRNA levels. Furthermore, central (intracerebroven-tricular) administration of the α7 nAChR agonist, even 2 h after LPS injection, attenuated the decrease in social exploratory behavior and microglial activation induced by peripheral administration of LPS, although this recovery was not achieved if activation of α7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of α7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of α7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation seems to be dysfunctional in microglia of aged mice., This work was supported by the Spanish Ministry of Science, innovation and Universities Ref. SAF2015-63935-R and Ref. RTI2018-095793-B-I00 and General Council for Research and Innovation of the Community of Madrid and European Structural Funds Ref. B2017/BMD–3827–NRF24ADCM to M.G.L. Aging studies were supported by an NIA grant (R01-AG-033028) to J.P.G .

Background Prevalence of cardiovascular disease risk factors and rates of atherosclerotic cardiovascular disease outcomes vary across racial/ethnic groups. This analysis examined the effects of evolocumab on LDL‐C (low‐density lipoprotein cholesterol) levels and LDL‐C goals achievement by race/ethnicity. Methods and Results Data from 15 phase 2 and 3 studies of treatment with evolocumab versus placebo or ezetimibe were pooled (n=7669). Results were analyzed by participant clinical characteristics and by self‐identified race/ethnicity. Key outcomes included percent change from baseline in LDL‐C, achievement of LDL‐C P values were nonsignificant, indicating consistent directionality of effect. Conclusions Similar reduction in LDL‐C levels with evolocumab was observed across racial/ethnic groups in 12‐week and 1‐ to 5‐year studies. Among those with diabetes mellitus, Asian participants had greater LDL‐C reduction.

A new SARS-CoV-2 variant, B.1.1.7, emerged in September in the UK, and is responsible for 76.6% of COVID-19 cases.1 This variant has also been reported in another 45 countries, 17 of them European.2,3 B.1.1.7 is considered to have higher transmissibility.4 It carries an unusually high number of specific mutations/deletions, 18, mostly non-synonymous and eight concentrate in the S gene,5 including several which might have relevant functional roles. The 69/70 deletion may be associated to immune response evasion6 and the N501Y substitution increases the affinity to the ACE2 receptor.7 These findings have raised the alarm of having to face a new variant with the potential to accelerate the spread of the pandemic. A recent report finds a realistic possibility that B.1.1.7 is associated with an increased risk of death., This work was supported by Instituto de Salud Carlos III (Ref COV20/00140: SeqCOVID—Consorcio para la epidemiología genómica de SARS-CoV-2 en España) and by Consejo Superior de Investigaciones Científicas (CSIC) (PTI Salud Global). LPL holds a Miguel Servet Contract CP15/00075).

Objective: Several studies have linked metabolic syndrome to the development of osteoarthritis (OA) through hypercholesterolemia, one of its components. However, epidemiological studies showed contradictory results, and it is not clear how hypercholesterolemia itself, or oxidized LDL (oxLDL)-a pathological molecule potentially involved in this relationship-could be affecting OA. The objectives of this study were to investigate the effect of hypercholesterolemia induced by high-fat diet (HFD) in cartilage from OA rabbits, and how oxLDL affect human chondrocyte inflammatory and catabolic responses. Design: New Zealand rabbits were fed with HFD for 18 weeks. On week 6, OA was surgically induced. At the end of the study, cartilage damage and IL-1β, IL-6, MCP-1, MMP-13, and COX-2 expression in articular cartilage were evaluated. In addition, cultured human OA articular chondrocytes were treated with oxLDL at concentrations equivalent to those expected in synovial fluid from HFD rabbits, in the presence of IL-1β and TNFα. The effect of oxLDL on cell viability, nitric oxide production and catabolic and pro-inflammatory gene expression was evaluated. Results: HFD intake did not modify cartilage structure or pro-inflammatory and catabolic gene expression and protein presence, both in healthy and OA animals. OxLDL did not affect human chondrocyte viability, ADAMTS5 and liver X receptor (LXR) α gene expression, but decreased the induction of IL-1β, IL-6, MCP-1, MMP-13, iNOS, and COX-2 gene expression and MMP-13 and COX-2 protein presence, evoked by cytokines. Conclusions: Our data suggest that cholesterol intake per se may not be deleterious for articular cartilage. Instead, cholesterol de novo synthesis and altered cholesterol metabolism could be involved in the associations observed in human disease.

Despite statin therapy, many patients with atherosclerotic cardiovascular disease (ASCVD) still suffer from ASCVD events. Predictors of residual ASCVD risk are not well-delineated. We aimed to develop an ASCVD risk prediction model for patients with prior ASCVD on statin use. We utilized statin-treated patients with ASCVD from the AIM-HIGH trial cohort. A 5-year risk score for subsequent ASCVD events with known ASCVD was developed using Cox regression, including potential risk factors with age, sex, and race forced in the model. Internal discrimination and calibration were evaluated. We included 3,271 patients with ASCVD (85.4% male, mean age 63.6 years, 65% on moderate and 24% on high-intensity statin) with complete risk factor data and mean follow-up of 4.18 years. Overall, the estimated 5-year ASCVD risk was 21.1%: 10.2% of patients had a 5-year risk of >30%, and 38.8% had risk of between 20-30%. In the model, male sex, hemoglobin A1c, alcohol use (inversely), family history of cardiovascular disease, body mass index, serum creatinine, homocysteine, history of heart failure, history of carotid artery disease and lipoprotein(a) predicted residual ASCVD risk. Niacin treatment status did not enter the model. A C-statistic of 0.59 was obtained, with the Greenwood-Nam-D’Agostino test showing excellent calibration. We developed a risk prediction risk model for predicting 5-year residual ASCVD risk in statin-treated patients with known ASCVD that may help in identifying such persons at the highest risk of recurrent events. Validation in larger samples with patients on high-intensity statin is needed.

In statin-treated persons with atherosclerotic cardiovascular disease (ASCVD) the further ASCVD risk that diabetes mellitus (DM) adds is not well-quantified. We examined this residual risk for initial and total recurrent ASCVD events.We studied 3271 patients with ASCVD on statin therapy in the AIM-HIGH clinical trial cohort. Cox regression and the Prentice, Williams, and Peterson model examined the excess risk of initial and total recurrent ASCVD events associated with DM over a 3- year mean follow-up. Predictors of first and total ASCVD events in those with and without DM were also examined.Of our cohort with ASCVD on statin therapy 40% also had DM. Those with vs. without DM were older, were less likely to be male or white. They had higher systolic blood pressure, lower HDL-C, LDL-C, lipoprotein (a), but higher triglycerides and BMI (all p 0.01). Adjusted HRs were 1.21 (95% CI; 1.01-1.46, p = 0.038) and 1.23 (95% CI: 1.05-1.44, p = 0.012) for first and total recurrent ASCVD events, respectively. Homocysteine and lipoprotein(a) most strongly predicted events in those with and without DM, respectively.In statin-treated patients with ASCVD, DM was associated with significantly greater residual risk over ASCVD alone for both first and total recurrent ASCVD events.

Background Dyslipidemia guidelines recommend non‐high‐density lipoprotein cholesterol (non‐ HDL ‐C) and apolipoprotein B (ApoB) as additional targets of therapy and consider lipoprotein(a) a significant cardiovascular risk marker. The current analysis evaluates the effects of evolocumab on these parameters in various patient populations over time. Methods and Results Data from 7690 patients, 4943 of whom received at least 1 dose of evolocumab, in 15 phase 2 and phase 3 studies with a duration ranging from 12 weeks to 5 years were pooled based on study length, patient population, and ezetimibe or placebo comparator groups. Patients could receive intensive statin therapy but not in the statin intolerance and monotherapy studies. The effects of evolocumab on percent change from baseline for non‐ HDL ‐C, ApoB, and lipoprotein(a) and achievement of treatment goals for non‐ HDL ‐C and ApoB were examined. Compared with placebo, evolocumab at both approved dosing regimens substantially reduced mean non‐ HDL ‐C (Q2W dose: −49% to −56%, monthly dose: −48% to −52%), mean ApoB (Q2W dose: −46% to −52%, monthly dose: −40% to −48%), and median lipoprotein(a) (Q2W dose: −22% to −38%, monthly dose: −20% to −33%) at 12 weeks. Effects on all 3 parameters persisted over 5 years. Lipid‐lowering effects were consistent among the patient populations examined (hypercholesterolemia/mixed dyslipidemia, statin intolerance, heterozygous familial hypercholesterolemia, and type 2 diabetes mellitus). Conclusions In this pooled analysis, evolocumab substantially reduced non‐ HDL ‐C, ApoB, and lipoprotein(a) compared with placebo. The effect was consistent and maintained in various patient populations over 5 years.

Evolutionary Algorithms (EAs) and other kind of metaheuristics are utilized to either design or optimize the architecture of Artificial Neural Networks (ANNs) in order to adapt them for solving a specific problem; these generated ANNs are known as Evolutionary Artificial Neural Networks (EANNs). Their architecture components, including number of neurons or their kind of transfer functions, connectivity pattern, etc., can be defined through direct or indirect encoding schemes; the former, directly codifies ANN architecture components into the genotype of solutions, meanwhile the last one, requires to transform the solution’s genotype through mapping processes to generate an ANN architecture. In this work, architectures of three-layered feed-forward ANNs are designed by using both encoding schemes to solve several well-known benchmark datasets of supervised classification problems. The results of designed ANNs by using direct and indirect encoding schemes are compared.

International audience; Background: People living with human immunodeficiency virus (PLHIV) are at higher risk of atherosclerotic cardiovascular disease (ASCVD) due to traditional and HIV- or antiretroviral treatment (ART)-related risk factors. The use of high-intensity statin therapy is often limited by comorbidities and drug-drug interactions with ART. Herein, we present the design and baseline characteristics of the BEIJERINCK study, which will assess the safety and efficacy of evolocumab in PLHIV and hypercholesterolemia/mixed dyslipidemia.Methods: Randomized, double-blind, placebo-controlled, multinational trial that investigates monthly subcutaneous evolocumab 420 mg versus placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia who are treated with maximally-tolerated statin therapy. The primary outcome is the baseline to week 24 percent change in low density lipoprotein cholesterol (LDL-C). Secondary outcomes include achievement of LDL-C < 70 mg/dL and percent change in other plasma lipid and lipoprotein levels. Safety will also be examined.Results: This study enrolled and dosed 464 patients who had a mean age of 56.4 years and were mostly male (82.5%). Mean duration with HIV was 17.4 years, and, by design, HIV viral load at screening was ≤50 copies/mL. ASCVD was documented in 35.6% of patients. Mean LDL-C of enrolled patients at baseline was 133.3 mg/dL. Statin use was prevalent (79.3% overall) with 74.6% receiving moderate or high-intensity statins. In total, 20.7% of patients did not receive statins due to intolerance/contraindications.Conclusions: The BEIJERINCK study is the first clinical trial to examine the lipid-lowering efficacy and safety of a fully human PCSK9 monoclonal antibody inhibitor in a moderate/high cardiovascular risk population of PLHIV.

Constituting nature-inspired computational systems, Artificial Neural Networks (ANNs) are generally classified into several generations depending on the features and capabilities of their neuron models. As generations develop, newer models of ANNs portrait more plausible properties than their predecessors, accounting for closer resemblance to biological neurons or for augmentations in their problem-solving abilities. Evolutionary Artificial Neural Networks (EANNs) is a paradigm to design ANNs involving Evolutionary Algorithms (EAs) to determine inherent aspects of the networks such as topology or parameterization, while prescinding—totally or partially—from expert proficiency. In this paper a comparison of the performance of evolutionary-designed ANNs from the second and third generations is made. An EA-based technique known as Grammatical Evolution (GE) is used to automatically design ANNs for solving supervised classification problems. Partially-connected three-layered feedforward topologies and synaptic connections for both types of considered ANNs are determined by the evolutionary process of GE; an explicit training task is not necessary. The proposed framework was tested on several well-known benchmark datasets, providing relevant and consistent results; accuracies exhibited by third-generation ANNs matched or bested those from second-generation ANNs. Furthermore, produced networks achieved a considerable reduction in the amount of existing synapses, as in comparison with equivalent fully-connected topologies, and a lower usage of traits from the input vector.

Chronic neuroinflammation is a hallmark of the onset and progression of brain proteinopathies such as Alzheimer disease (AD) and it is suspected to participate in the neurodegenerative process. Transcription factor NRF2, a master regulator of redox homeostasis, controls acute inflammation but its relevance in low-grade chronic inflammation of AD is inconclusive due to lack of good mouse models. We have addressed this question in a transgenic mouse that combines amyloidopathy and tauopathy with either wild type (AT-NRF2-WT) or NRF2-deficiency (AT-NRF2-KO). AT-NRF2-WT mice died prematurely, at around 14 months of age, due to motor deficits and a terminal spinal deformity but AT-NRF2-KO mice died roughly 2 months earlier. NRF2-deficiency correlated with exacerbated astrogliosis and microgliosis, as determined by an increase in GFAP, IBA1 and CD11b levels. The immunomodulatory molecule dimethyl fumarate (DMF), a drug already used for the treatment of multiple sclerosis whose main target is accepted to be NRF2, was tested in this preclinical model. Daily oral gavage of DMF during six weeks reduced glial and inflammatory markers and improved cognition and motor complications in the AT-NRF2-WT mice compared with the vehicle-treated animals. This study demonstrates the relevance of the inflammatory response in experimental AD, tightly regulated by NRF2 activity, and provides a new strategy to fight AD., This work was funded by SAF2016-76520-R of the Spanish Ministry of Economy and Competitiveness, a Pathfinder grant of the Centres of Excellence in Neurodegeneration (COEN) of the EU-Joint Program for Neurodegenerative diseases, and European Regional Development Fund, Competitiveness Operational Program 2014–2020, through the grant P_37_732/2016 REDBRAIN and a collaborative CIBERNED project PI2017/04-3. M.P. is recipient of a FPU fellowship of Autonomous University of Madrid.

Background With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. Methods The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. Results The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference – all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6–11 years and ≥12 years. Conclusions For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

Bioethanol for use in vehicles is becoming a substantial part of global energy infrastructure because it is renewable and some emissions are reduced. Carbon monoxide (CO) emissions and total hydrocarbons (THC) are reduced, but there is still controversy regarding emissions of nitrogen oxides (NOThe use of bioethanol can significantly reduce petroleum use and greenhouse gas emissions worldwide. Given the extent of its use, it is important to understand its effect on urban pollution. There is a controversy on whether there is a reduction or increase in PM emission when using ethanol blends. Primary emissions of THC, CO, CO

Background and aims Saffron is an antioxidant herbal derivative; however, its efficacy as a nutritional cardioprotective agent has not been fully elucidated. We investigated the cardioprotective properties of a standardized saffron aqueous extract (SFE) against ischemia/reperfusion (I/R) injury in Wild-Type (WT) and ApoE (−/−) mice and the underlying molecular mechanisms. Methods and results WT and ApoE (−/−) mice were subjected to 30 min I and 2 h R, with the following per os interventions for 4 weeks: 1) WT Control Group, receiving Water for Injection (WFI); 2) WT Crocus Group, receiving SFE at a dose of 60 mg/kg/day; 3) WT Crocus + Wort group, receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus 15 min before R; 4) ApoE (−/−) Control Group, receiving WFI; 5) ApoE (−/−) Crocus Group, receiving SFE at a dose of 60 mg/kg/day and 6) ApoE (−/−) Crocus + Wort: receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus, 15 min before R. Ischemic area/area at risk (I/R%) ratio was measured. Blood samples and ischemic myocardial tissue were collected at the 10th min of reperfusion for assessment of troponin I, malondialdehyde (MDA), nitrotyrosine (NT), p-eNOS, eNOS, p-Akt, Akt, p-p42/p-p44, p-GSK3β, GSK3β, IL-6, Nrf2, HO-1 and MnSOD expression. The effect of SFE on Nrf2 expression was also evaluated in vitro . SFE reduced infarct size in WT (16.15 ± 3.7% vs 41.57 ± 2.48%, ***p (−/−) mice (16.14 ± 1.47% vs 45.57 ± 1.73%, ***p (−/−) mice). Mice receiving SFE showed increased levels of eNOS, p-Akt, p-ERK1/2, p-44/p-42 and p-GSK3β-Ser9 and reduced expression of IL-6 and iNOS; furthermore, SFE reduced the levels of MDA and NT. SFE induced Nrf2 expression and its downstream targets, HO-1 and MnSOD in the myocardium of the treated animals, and induced Nrf2 expression in vitro in a dose-dependent manner. Conclusions SFE limits myocardial infarction in Wild-Type and ApoE (−/−) mice in a multifaceted manner including activation of Akt/eNOS/ERK1/2/GSK3-β and through Nrf2 pathway, bestowing antioxidant protection against I/R.

This article presents a hybrid classification method combining image segmentation, GIS analysis, and visual interpretation, and its application to elaborate a multi-date cartographic database with 23 land use/cover (LUC) classes using SPOT 5 imagery for the Mexican state of Michoacan (~60,000 km2). First, the resolution of an existing 1:100,000 LUC map produced through visual interpretation of 2007 SPOT images was improved. 2007 SPOT images were segmented, and each segment received the “majority” LUC category from the 1:100,000 map. Segments were characterized from the images (spectral indices) and the map (LUC class). A multivariate trimming was applied to detect “uncertain” segments presenting discrepancy between their spectral response and the LUC class assigned from the map. For these uncertain segments, a category was determined by digital classification, but a definitive category was assigned through visual interpretation. Finally, accuracy of the resulting LUC map was assessed. The same procedure was applied to downgrade (2004) and to update (2014) the map. The implemented method enabled us to improve the scale of an existing 2007 LUC map and to detect land use/cover changes in previous (downgrading) and later (updating) dates with an overall accuracy of 83.3% ± 3.1%.

We present the case of a 52-year-old woman referred to our service because of extreme ocular surface dryness. The patient showed corneal, conjunctival, and eyelid manifestations of ocular congenital erythropoietic porphyria (CEP). We started treatment with autologous serum, topical steroids, and cyclosporine twice a day, topical retinoids, and intense corneal lubrication. The patient referred significant improvement of ocular bothering and less discomfort since treatment was initiated. We describe the management of the herewith presented case of ocular CEP. © 2019 Indian Journal of Ophthalmology.