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Background: Cardiac amyloidosis (CA), following a non-invasive diagnosis, constitutes an increasingly prevalent heart failure (HF) etiology. This study aims to determine which echocardiography findings help to diagnose cardiac amyloidosis in patients with left ventricular hypertrophy (LVH) admitted for decompensated HF. M ethods: The present study is a retrospective observational study on a cohort of 85 LVH patients admitted for HF decompensation, in which 99m Tc-DPD scanning was performed to rule out transthyretin CA. The echocardiographic findings obtained were compared between CA and non-CA groups. Results: From a total number of 85 patients, 49 (57.6%) met the CA criteria and 36 (42.3%) were ruled out for the disease. Interventricular septum thickness (16 ± 3 mm vs. 14 ± 3 mm), left ventricular posterior wall thickness (14 ± 3 mm vs. 11 ± 2 mm), left ventricular mass (259 ± 76 g vs. 224 ± 53 g), left ventricular telediastolic diameter (48 ± 7 mm vs. 53 ± 6 mm), left ventricular telediastolic indexed volume (51 ± 18 cm 3 /m 2 vs. 59 ± 16 cm 3 /m 2 ), tricuspid annular plane systolic excursion (16 ± 5 mm vs. 20 ± 4 mm), right atrial area (27.4 ± 8.4 cm 2 vs. 22.2 ± 5.7 cm 2 ) and strain relative apical sparing (2.2 ± 0.9 vs. 1.03 ± 0.4; p = 0.04) were significantly associated with the diagnosis of CA. Conclusions: In patients with LVH admitted for HF decompensation, there are several echocardiographic features (LVH, reduced left ventricular cavity size, strain relative apical sparing, right atrial dilation, and altered right ventricular function) that are associated with the diagnosis of cardiac amyloidosis.

Resumen Introduccion y objetivos La amiloidosis hereditaria por transtirretina (ATTRv) es una enfermedad causada por mutaciones en el gen de la transtirretina que frecuentemente presenta afeccion cardiaca debido al deposito de amiloide en el miocardio. Nuestro objetivo es describir esta afeccion en una cohorte espanola. Metodos Estudio retrospectivo multicentrico de pacientes con ATTRv y afeccion cardiaca provenientes de centros espanoles. Se recogieron datos demograficos, clinicos y geneticos. Resultados En 26 centros se incluyo a 181 pacientes, el 65,2% varones, con una mediana de edad al diagnostico de 62 anos. Las mutaciones mas frecuentes fueron Val50Met (67,7%) y Val142Ile (12,4%). El principal motivo de consulta fue extracardiaco (69%), principalmente neurologico. La media de la fraccion aminoterminal del propeptido natriuretico cerebral (NT-proBNP) fue 2.145 ± 3.586 pg/ml. Lo mas caracteristico del electrocardiograma fueron el patron de seudoinfarto (25,9%) y el bloqueo auriculoventricular (25,3%). El grosor ventricular medio fue 15,4 ± 4,1 mm. El strain longitudinal estaba reducido en segmentos basales en el 29,4%. Se observo realce tardio subendocardico difuso en el 58,8%. En la gammagrafia habia captacion de grados 2-3 en un 75%. En el seguimiento, el 24,9% ingreso por insuficiencia cardiaca, el 34,3% preciso marcapasos y el 31,6%, trasplante hepatico. El 32,5% fallecio, principalmente por insuficiencia cardiaca (28,8%). Las mutaciones diferentes de Val50Met se asociaron en general con un peor pronostico. Conclusiones La ATTRv cardiaca en Espana tiene un espectro genetico y de afeccion heterogeneo. El pronostico es malo principalmente por las complicaciones cardiacas, por lo que son esenciales un diagnostico y un tratamiento precoces.

Introduction and objectives Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. Methods Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. Results A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis. Conclusions HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital.

Background and objective Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them. Material and methods Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020. Results A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas. Conclusions ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

Resumen Antecedentes y objetivo La amiloidosis por transtiretina (ATTR) es una enfermedad rara que forma parte de las amiloidosis sistemicas, y es una enfermedad amenazante para la vida. Puede afectar a todos los organos y sistemas, siendo la mas frecuente la afectacion neurologica y cardiaca. El objetivo de este estudio es detectar posibles casos de ATTR y realizar un estudio descriptivo de los mismos. Material y metodos Estudio descriptivo unicentrico realizado en un hospital de tercer nivel en el que se incluyen pacientes con sospecha de ATTR entre septiembre de 2016 y enero de 2020. Resultados Se detectan 190 pacientes sospechosos de ATTR. En el estudio se incluyen 100 de ellos, asi como 10 familiares de pacientes en los que se detecta ATTR en su variante genetica. En total, se detecta ATTR variante genetica en 7 individuos (3 con mutacion presintomatica de la enfermedad), 16 pacientes con ATTR asociada a la edad y 31 individuos con amiloidosis cardiaca no filiada con las pruebas realizadas, lo que confirma la presencia de esta enfermedad en areas no endemicas. Conclusiones La ATTR es una enfermedad que se ha de tener en cuenta en el diagnostico diferencial de pacientes que presentan insuficiencia cardiaca con FEVI preservada, principalmente si se asocia a sintomas neurologicos.

Aims: Microalgae are ubiquitous in aquatic environments, including aquaculture farms, but few studies have delved into their phytoplankton diversity and bioremediation potential. In this study, the cultivable phytoplankton of a rainbow trout freshwater aquaculture farm was isolated, phylogenetically analysed and used to assemble a consortium to polish an aquaculture derived effluent, with low concentrations of ammonium, nitrite and nitrate. Methods and Results: Through standard plating in different selective media, a total of 15 microalgae strains were isolated from sludge from a rotary drum filtering system which removes suspended solids from the water exiting the facility. Based on 18S rRNA gene sequences, isolates were assigned to nine different genera of the Chlorophyta phylum: Asterarcys, Chlorella, Chloroccocum, Chlorosarcinopsis, Coelastrella, Desmodesmus, Micractinium, Parachlorella and Scenedesmus. Species from most of these genera are known to inhabit freshwater systems in Galicia and continental Spain, but the Coelastrella, Asterarcys or Parachlorella genera are not usually present in freshwater streams. In an onsite integrative approach, the capacity of a consortium of native microalgae isolates to grow on aquaculture derived effluents and its nutrient removal capacity were assessed using a raceway pond. After 7 days, removal efficiencies of approximately 99%, 92% and 49% for ammonium, nitrite and nitrate, respectively, were achieved concomitantly with a microalgae biomass increase of ca. 17%. Conclusions: Sludge from the aquaculture filtering system presents a high diversity of microalgae species from the Chlorophyta phylum, whose application in a consortial approach revealed to be efficient to polish aquaculture derived effluents with low nutrient content. Significance and Impact of the Study: The use of native microalgae consortia from aquaculture systems can contribute to the development of efficient treatment systems for low nutrient wastewater, avoiding nutrients release to the environment and promoting water recirculation. This may further strengthen the use of phycoremediation at the industrial scale, as an environment friendly strategy.

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world, and the bacterial microbiome has been considered a risk factor that could play an important role in carcinogenesis. Objective: A bacteriome study was performed by next-generation sequencing in dental plaque, saliva, and tumor samples of 10 OSCC patients and compared with bacteriome in dental plaque and saliva of 10 patients without OSCC. Methods: DNA was extracted from all samples and sequenced by Illumina technology MiSeq™. Bioinformatic analyzes were performed for evaluated sequence quality, alpha and beta diversity, bidirectional analysis of variance (p Results: Out of the identified 1,231 bacteria in the populations under study, 45 bacterial species were selected, of which 34 were compatible with eubiosis, and 11 were compatible with dysbiosis. Among the bacteria compatible with eubiosis were species of Lactobacillus and Streptococcus, Chromobacterium violaceum, Enterobacter asburiae, Mycobacterium chubuense, Mycoplasma penetrans, and Brachyspira intermedia. Among the species associated with dysbiosis, Providencia stuartii, Capnocytophaga canimorsus, Legionella pneumophila, and Mycoplasma hominis were notable. Conclusion: Thirty-four bacterial species may be associated with eubiosis or healthy states and 11 bacterial species could be associated with dysbiosis or pathogenic state, OSCC.

While life expectancy increases in developed countries and there is evidence that demon strates the potential of the internet to optimise or compensate for the losses associated with ageing, there is a high proportion of older people who continue to be disconnected from the digital world. In this scenario, the technological support offered by public insti tutions has the potential to be an accessible source for the digital literacy of older people. This study, using the model of digital inequality, had the aim of analysing the ability of these institutional supports to determine and predict the digital inclusion of older people. The sample was retired adults (over 54 years) residing in Spain who are users of techno logical support services in four organisational contexts: nursing homes, senior community centres, University Programs for Seniors and adult education programmes. Through bin ary logistic regression analysis, we found that the ability of the availability of literacy sup port to determine and predict access, autonomy, skills and use of the internet for social connectivity depends on the social and organisational context of the technology support service. These findings support empirically the situated nature of technological support for the digital inclusion of older people and provide a useful comparative vision for the design of accessible support services adapted to the needs of its users., This work was conducted within the framework of ‘Alfamed’ (Euro-American Network of Researchers), with the support of the R+D Project ‘Youtubers and Instagrammers: Media Competence in Emerging Prosumers’ (RTI2018-093303-B-I00), financed by the State Research Agency of the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund.

Germline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown. We performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Maranon, Spain, from 2010 to 2019. One-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients. The VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.

In current clinical guidelines, such as those provided by the National Comprehensive Cancer Network (NCCN), evidence for treatment is based on a small clinical trial that included patients with HLRCC. They support the use of the combination of erlotinib and bevacizumab as the first therapeutic option in this rare condition. In the present study, we report a rare case of this condition in an 18-year-old male with a family history of kidney cancer whom we successfully treated with surgery and a novel drug treatment modality based on the combination of an immune check-point inhibitor (ICPI) and a tyrosine-kinase inhibitor (TKI) with excellent and promising results.

While social support—friends, family, and colleagues—is one of the main sources of encouragement and digital literacy for older people, there is evidence that suggests that they may prefer formal sources of support. This study aims to verify the capacity of technological support services to promote literacy and Internet use by older people in multiple contexts. The participants ( N = 560) were retired adults (over 54) residing in Spain and habitual users of technological support services in four organizational contexts (nursing homes, community senior centers, university programs for seniors, and adult education programs). The results show the moderating role of organizational contexts on the capacity of formal technological supports to determine the use and appropriation of the Internet by older people. Finally, the findings are discussed in terms of their usefulness for initiatives that adapt to the needs of the users of these services.

The exploration of unexploited geothermal resources is required to encourage the use of renewable energy. This study focuses on La Jolla beach, Ensenada, Mexico. The beach hosts a thermal anomaly with temperatures of up to 52 °C at the surface and up to 93 °C at 20 cm depth. The objectives were to: map the thermal anomaly, understand the impact of tides, quantify the thermal water discharge rate and heat output, and discuss a direct use of the energy. The mapping was performed with Unmanned Aerial Vehicles equipped with optical and thermal cameras at two different dates. Additional temperature measurements were performed with a thermocouple, while the total fluid discharge was estimated from flow measurements. A comparison between the campaigns indicated that the highest surface temperature area was more than three times larger in 2019 than in 2018 (259 m2 vs. 69 m2). Such change was due to the tidal range and associated hydrostatic pressure variations. The total thermal water discharge is 330 ± 44 L s−1, which corresponds to an advective heat output of 40.5 ± 5.2 MWt. The use of this energy in a Multi-Effect Distillation desalinization plant can contribute to cover the shortage of freshwater in Ensenada.

Neoepitopes or neoantigens are a spectrum of unique mutations presented in a particular patient’s tumor. Neoepitope-based adoptive therapies have the potential of tumor eradication without undue damaging effect on normal tissues. In this context, methods based on the T cell receptor (TCR) engineering or chimeric antigen receptors (CARs) have shown great promise. This review focuses on the TCR-like CARs and TCR-CARs directed against tumor-derived epitopes, with a concerted view on neoepitopes. We also address the current limitations of the field to know how to harness the full benefits of this approach and thereby design a sustained and specific antitumor therapy.

A subset of oncogenic human papillomaviruses (HPVs) is the main cause of genital cancers, most importantly cervical cancer and an increasing number of head and neck cancers. Despite the availability of prophylactic vaccines against the most prevalent oncogenic HPV types, HPV‐induced malignancies are still a major health and economic burden. Besides conventional treatment with surgery, chemotherapy and radiation, immunotherapy is emerging as an efficient adjuvant option. Here, we review relevant studies and ongoing clinical trials using immune checkpoint inhibitors, therapeutic vaccines, gene editing approaches and adoptive T cell therapies, with special focus on engineered TCR T cells, which are showing encouraging results and could lead to significant improvement in the treatment of HPV+‐infected cancer patients., Most therapeutic vaccines targeting oncogenic HPVs are still in early clinical studies. Antibodies against immune checkpoint inhibitors have sown some success. A combination of different immunotherapeutic approaches will be needed to overcome current limitations in the immunotherapy of HPV‐associated cancers.

Autism Spectrum Disorder (ASD) and epilepsy are two neurodevelopmental disorders that have a high comorbidity rate, suggesting that a common neurodevelopmental mechanism exists. However, to date there is no conclusive way to predict whether a child will develop either syndrome or both and to what degree associated phenotypes will be affected. Failure to consistently identify predictive patterns of ASD and/or epilepsy diagnosis stems from the fact that they are etiologically heterogeneous conditions and research into their neuropathological mechanisms becomes challenging. Whole genome/exome sequencing has advanced our understanding of the genetic causes of ASD and epilepsy to an extent that currently about half of all ASD as well as epilepsy cases are known to have a genetic basis. In fact, a picture is emerging of both conditions as a collection of distinct genetically defined disorders, although the role of environmental factors has also been established. A plethora of animal models, most of them based on identified human genetic mutations and a few on known environmental causes, have been developed. Animal models provide a major experimental avenue for studying the underlying cellular and molecular mechanisms of human disorders. They also provide invaluable preclinical tools that can be used to test therapeutic approaches. In this review, we first summarize the methods for validating mouse models of ASD and epilepsy. Second, we present the current models validated for the comorbidity and finally, we recapitulate the common pathomechanisms identified in these models with special emphasis on synaptic plasticity.

Background: The development of cystic fibrosis (CF)-related diabetes (CFRD) in paediatric groups is associated with a reduced aerobic fitness. However, this has yet to be investigated in adults with more severe lung disease.Methods: Cardiopulmonary exercise and glycaemic control tests were retrospectively analysed in 46 adults with CF (age: 26.9 y [range: 16.3–66.5 y]; forced expiratory volume in 1s: 65.3% [range: 26.8–105.7%]; 26 males), diagnosed with CFRD (n = 19), impaired glucose tolerance (IGT; n = 8) or normal glucose tolerance (NGT; n = 19). Results: Maximal oxygen uptake (V ̇O2max) was reduced in adults with IGT and CFRD compared to their age- and gender-matched counterparts with NGT (p < 0.05); however, there was no difference when lung function was included as a covariate (all p > 0.05). V ̇O2max was greater in adults who experienced post-reactive hypoglycaemia vs. NGT without hypoglycaemia (p < 0.05). The frequency of ventilatory limitation (84%, 63% and 37%, respectively; p < 0.05) but not ventilation-perfusion mismatch (42%, 38% and 16%, respectively; p > 0.05), was greater with CFRD and IGT vs. NGT. There was also no difference in arterial oxygen saturation changes between groups (p > 0.05). Gender and body mass index were significant predictors of V ̇O2max (adjusted R2 = 0.37, p < 0.01), but glycaemic control did not explain additional variance (p > 0.05).Conclusions: Adults with CF-related dysglycaemia had a reduced V ̇O2max compared to age- and gender-matched counterparts, due to a greater degree of CF lung disease in these populations.

Controlling thermal energy transfer at the nanoscale and thermal properties has become critically important in many applications since it often limits device performance. In this study, the effects on thermal conductivity arising from the nanoscale structure of free-standing nanocrystalline silicon films and the increasing surface-to-volume ratio when fabricated into suspended optomechanical nanobeams are studied. Thermal transport and elucidate the relative impact of different grain size distributions and geometrical dimensions on thermal conductivity are characterized. A micro time-domain thermoreflectance method to study free-standing nanocrystalline silicon films and find a drastic reduction in the thermal conductivity, down to values below 10 W m–1 K–1 is used, with a stronger decrease for smaller grains. In optomechanical nanostructures, this effect is smaller than in membranes due to the competition of surface scattering in decreasing thermal conductivity. Finally, a novel versatile contactless characterization technique that can be adapted to any structure supporting a thermally shifted optical resonance is introduced. The thermal conductivity data agrees quantitatively with the thermoreflectance measurements. This study opens the way to a more generalized thermal characterization of optomechanical cavities and to create hot-spots with engineered shapes at the desired position in the structures as a means to study thermal transport in coupled photon-phonon structures., This work was supported by the European Commission FET Open project PHENOMEN (G.A. Nr. 713450). ICN2 was supported by the S. Ochoa program from the Spanish Research Agency (AEI, grant no. SEV-2017-0706) and by the CERCA Programme / Generalitat de Catalunya. ICN2 authors acknowledge the support from the Spanish MICINN project SIP (PGC2018-101743-B-I00). D.N.U. and M.F.C. acknowledge the support of a Ramón y Cajal postdoctoral fellowship (RYC-2014-15392) and a Severo Ochoa studentship, respectively. E.C.A. acknowledges financial support from the EU FET Open Project NANOPOLY. (GA 829061). A.M. acknowledges support from Ministerio de Ciencia, Innovación y Universidades (grant PGC2018-094490-B, PRX18/00126) and Generalitat Valenciana (grants PROMETEO/2019/123, and IDIFEDER/2018/033).

Background. The study of the deformation of curved rods subjected to bending and its associated stress state is a complex task that has not been treated in depth in the literature, which makes difficult to obtain constitutive models or Finite Element Models (FEM) in which it is necessary to know all the components of the stress and strain tensors. Objectives. This study focuses on a new calculation methodology to obtain stress and strain tensors of curved rods under bending. Methods. The stress and strain tensors have been determined based on the theory of continuum mechanics and differential geometry of curves (moving bases), in a general methodology and valid for large strains, curved geometries and variable cross-sections along the specimen. This has been applied to the human rib and, in addition, a new experimental method for bending of curved specimens based on Digital Image Correlation (DIC) is presented. Results. Both the test method and the proposed calculations applied to the human rib show results according to expectations, allowing to know the rib curvature changes along the test, the stresses and strains along the rib and the components of both stress and strain in all directions, in order to build the stress and strain tensors. In addition, the results of stress, strain and young’s modulus correspond to those of previous literature in tensile testing of human rib cortical bone. Conclusions. The proposed calculations allow the construction of the strain and stress tensors of a curved specimen subjected to bending, which is of great importance for the development of constitutive models. Moreover, since with this method it is possible to calculate both tensors along the entire length of the specimen and in all directions, it is possible to apply this method in finite element models. Finally, the new test methodology allows to know the stress and strain in curved specimens such as the human rib, from bending tests.

Over the last half century, photography has evolved from photochemical reactions induced on a photosensitive film to optoelectronic devices employed in digital image. Video has done the same migration from classical film movies to optoelectronic acquisition and storage. Digital and video cameras share optics with traditional film cameras, but the image recording is realized by an optoelectronic device –a CCD or CMOS sensor– rather than a film. The quantity of digital photo and video images has dramatically increased in the last decade, arising from the ubiquitous cameras of mobile phones. Despite their popularity, condensed tutorial articles on the subject are still scarce. This work intends to contribute to the knowledge of this field with a medium-level short course that is currently being taughtin a broader subject (Consumer Photonics) to undergraduate students of Telecommunication Engineers at the Universidad Politecnica de Madrid. The course can be followed by students having a basic background on Physics and specifically on Optics and Semiconductors. The course is divided into two chapters. An introduction to optics of cameras and basic concepts of photography has been considered necessary to follow the second part, which is entirely devoted to optoelectronic sensors

In the previous chapter, we have browsed upon the optics of photographic cameras, focusing on the specific features of digital cameras and their sensors. We have also compared the camera performance with eye, including grayscale, sensitivity, dynamic range, field of view and many others. Eyes are far superior to cameras in several aspects, those favored by evolution, while cameras prevail in other aspects not so relevant for vision. Yet digital cameras are still quite similar to analog film-based cameras in all issues related to optics. In this part we will concentrate on the most distinctive element of modern digital cameras, the optoelectronic sensor. We will study the fundamentals of optoelectronic light to electric signal conversion, the different families of sensors and detection modes, their advantages and flaws. Finally we will show the current trends in sensors and explain the reasons why manufacturers have chosen them.

When the normal microbiota-host interactions are altered, the commensal microbial community evolves to a dysbiotic status resulting in some species becoming pathogenic and acting synergistically in the development of local and systemic diseases, including cancer. Advances in genetics, immunology and microbiology during the last years have made it possible to gather information on the oral and gastrointestinal microbiome and its interaction with the host, which has led to a better understanding of the interrelationship between microbiota and cancer. There is growing evidence in support for the role of some species in the development, progression and responses to treatment of various types of cancer. Accordingly, the number of studies investigating the association between oral microbiota and oral and gastrointestinal cancers has increased significantly during the last years. Here, we review the literature documenting associations of oral microbiota with oral and gastroenteric cancers.

Introduction: Children with surgically repaired esophageal atresia (EA) show esophageal dysmotility. Due to the performance of high-resolution manometry (HRM), three motility alteration patterns have been described, which allowed to know the segmental alterations. Objective: To describe the esophageal motility patterns found through HRM in teenagers with EA and to relate these with the associated esophageal pathology and its severity. Materials and Method: Ten teenagers were included with no history of esophageal blockage or dilations in the last six months, who were orally fed and asymptomatic. Through performance of HRM, we found surgical and endoscopic history, as well as of esophageal biopsies and pH monitoring. Results: We found the following patterns: aperistalsis, pressurization and distal contraction. 70% showed distal contraction, and 100% of esophageal endoscopies and biopsies were normal. 57% of the esophageal pH monitoring analyzed was pathologic. In the pressurization and aperistalsis groups, we observed severe esophagitis and requirement of Nissen antireflux procedure in 100% of the cases. Esophageal pH monitoring analyzed was 100% pathologic. Conclusion: We described the esophageal segmental alterations in teenagers with atresia by means of HRM. The distal contraction group showed better development, without severe esophagitis or requirement of antireflux procedure. Therefore, by performing an HRM in teenagers with EA, we could predict the future esophageal behavior, according to the peristaltic pattern, since there are significant differences among the groups in study.

The purpose of neurophysiological monitoring during surgery is to identify damage or functional neurological disturbances as soon as possible, ensuring spinal cord functionality and avoiding neurological complications. However, the lack of standardisation of the methodology, together with some inconsistencies in the studies on its usefulness, limit the establishment of universal recommendations for its use. The present paper intends to review neurophysiological monitoring procedures during surgery, including their strength and weaknesses, as well as to assess the convenience of their use during spinal surgery. It is concluded that, in general, the lack of its use in this surgery does not legally contravene the standard of care, as there is no evidence it could result in reverting neurological damage. Nevertheless, it can be used as evidence both in detecting the time and kind of neurological injury, and for increasing the defensibility. Protocols of use, provided either by scientific societies or hospitals themselves, are required.

The construction of a low-cost spectrophotometer as part of project-based teaching for postgraduate students in the field of Photonics Engineeringis depicted. The criteria followed in designing this project include considerations about budget, portability and multidisciplinary skills. The proposal has been carriedout in the context of a 3 credit Experimental Projects I course, part of the Master in Photonics Engineering taught by the Polytechnic University of Madrid, University Carlos III of Madrid and University of Alcala. During its performance, students have been supplied with all the necessary mechanical and optomechanical hardware, as well as passive and active optical elements and driving circuitry. Their tasks include the manufacture of a diffraction grating by a brand-new nanoimprint technique, the optimization of the optical alignment for improving the optical transfer function and the signal-to-noise ratio at the detection stage, and the programming of the control system and data acquisition in a LabView environment. The outcome is a fully functional spectrophotometer.Although it has been designed and tested with students of photonics, its multidisciplinary and modular character makes it useful also for undergraduate students from different disciplines, such as Industrial, Electronics or Automation Engineering. The open availability of the mechanical and electronic designs further allows its use by secondary teachers as a demonstrator of the different concepts used in their implementation (photonics, mechanics, electronicsand software).

This study aimed to investigate training-induced fitness changes and their relationship with training-competition load during half a soccer season (18 wks). Training load [heart rate (HR) and ratings of perceived exertion (RPE)] and match time were monitored, including 108 training (3 223 individuals) and 23 match sessions, in 38 youth elite male soccer players. Fitness variables were assessed before and after the study. Yo-Yo intermittent recovery test 1 (Yo-Yo IRT1) improved (P

Resumen Introduccion y objetivos La enfermedad valvular en los pacientes con fibrilacion auricular incluidos en los ensayos clinicos con anticoagulantes orales directos (ACOD) es frecuente y se asocia con peor pronostico. El objetivo es evaluar la prevalencia de valvulopatia y su influencia en los eventos clinicos en la practica clinica real. Metodos Registro multicentrico retrospectivo que incluyo a 2.297 pacientes consecutivos con fibrilacion auricular no valvular que iniciaron tratamiento con ACOD entre enero de 2013 y diciembre de 2016. La enfermedad valvular se definio como afeccion moderada o grave. El evento principal fue la combinacion de muerte, ictus o accidente isquemico transitorio/embolia sistemica o hemorragia mayor. Se realizo un analisis de riesgos competitivos mediante un modelo de regresion de Fine y Gray, con la muerte como evento competitivo. Resultados Tenian valvulopatia 499 pacientes (21,7%), y la insuficiencia mitral fue la mas frecuente (13,7%). Los pacientes con valvulopatia eran de mas edad y con mayor comorbilidad. Tras el analisis multivariable, la enfermedad valvular fue predictora del evento combinado (HR = 1,54; IC95%, 1,22-1,94; p 0,05). Conclusiones En pacientes con fibrilacion auricular no valvular que inician tratamiento con ACOD, la enfermedad valvular es frecuente y se asocia con mayor riesgo de muerte, ictus o accidente isquemico transitorio/embolia sistemica o complicaciones hemorragicas. Estos hallazgos confirman los resultados de los ensayos clinicos y los expande al ambito de la practica clinica real.

Body donation is in the basis of transplantation programs, founded on receptor and donor rights. Nevertheless, if the purpose is not directed to healthcare, the regulation is different both in live or deceased individuals. “Imaging techniques” generates digital files containing the “virtual body” of the patient, raising a new possibility: virtual body donation, which is not regulated in Spain and would not be compliant with legal requirements for other ways of donation. A pioneer program for virtual body donation is presented, analysing its characteristics, medico-legal issues, organisation and functioning. Having an unlimited number of virtual specimens (normal and pathological) could support a new way for teaching and research. These resources would also have the advantage of learning virtual biopsy (virtopsy). It is thought that these programs, pioneers in Spain, could be useful for introducing similar initiatives that would have unlimited applications in teaching and research both in forensic and morphological sciences.

Chimeric antigen receptor (CAR) T-cells represent a paradigm shift in cancer immunotherapy and a new milestone in the history of oncology. In 2017, the Food and Drug Administration approved two CD19-targeted CAR T-cell therapies (Kymriah™, Novartis, and Yescarta™, Kite Pharma/Gilead Sciences) that have remarkable efficacy in some B-cell malignancies. The CAR approach is currently being evaluated in multiple pivotal trials designed for the immunotherapy of hematological malignancies as well as solid tumors. To generate CAR T-cells ex vivo, lentiviral vectors (LVs) are particularly appealing due to their ability to stably integrate relatively large DNA inserts, and to efficiently transduce both dividing and nondividing cells. This review discusses the latest advances and challenges in the design and production of CAR T-cells, and the good manufacturing practices (GMP)-grade production process of LVs used as a gene transfer vehicle. New developments in the application of CAR T-cell therapy are also outlined with particular emphasis on next-generation allogeneic CAR T-cells.

Objective To analyse the evolution and adequacy of referrals from primary care to urology, after the implementation of referral protocols on the most frequent urological diseases and the establishment of a continuing education program. Material and methods A primary care-urology work group was created in 2011. Initially, performance and clinical practice protocols in prostatic pathology (BPH and PSA) were established. These were supported by training sessions for primary care physicians. After analysing the effect of the mentioned joint work, 3 more protocols (scrotal pathology, urinary tract infections and urinary incontinence) were included. We analysed and compared the referrals and their adequacy before and after the establishment of the protocols. Results The most common referral causes were symptoms of the lower urinary tract due to BPH, which initially represented 22.8% of the total, and decreased to 16.9%. After the introduction of the new algorithms, we observed a decrease in referrals for scrotal pathology (13–14% to 7.8%), an increase in urinary incontinence referrals (3–10.3%) and those related to urinary tract infections remained stable. The adequacy to the protocols improved progressively: LUTS from 46% to 65.3%; PSA from 55% to 84.4% and urinary incontinence from 66.2% to 73.1%. Adequacy in scrotal pathology decreased (67.1% to 63.3%), while in UTI it stayed much the same (around 76%). Conclusions The joint work between Urology and Primary Care achieves an improvement in referrals adequacy regarding the most frequent urological pathologies.

Resumen Objetivo Analizar la evolucion y adecuacion de las derivaciones de Atencion Primaria a Urologia tras la implantacion de protocolos sobre las enfermedades urologicas mas frecuentes y la instauracion de un programa de formacion continuada. Material y metodos En el 2011 se creo un grupo de trabajo Atencion Primaria-Urologia. Se instauraron inicialmente protocolos de actuacion y practica clinica en enfermedad prostatica (HBP y PSA), que se apoyaron con sesiones formativas a los medicos de Atencion Primaria. Tras analizar su efecto, en el 2015 se anadieron otros 3 (enfermedad escrotal, infecciones urinarias e incontinencia urinaria). Analizamos y comparamos las derivaciones y su adecuacion antes y despues de la instauracion. Resultados El motivo mas frecuente de derivacion son los sintomas del tracto urinario inferior (STUI) por HBP que, inicialmente, suponian un 22,8% del total, y que han disminuido al 16,9%. Tras la introduccion de los demas algoritmos, observamos una disminucion de las derivaciones sobre enfermedad escrotal (del 13-14 al 7,8%), que permanecen estables (en torno al 10%) las relacionadas con infecciones urinarias y que aumentan las derivaciones por incontinencia urinaria (del 3 al 10,3%). La adecuacion a los protocolos fue mejorando progresivamente en las relacionadas con STUI (del 46 al 65,3%); en PSA (del 55 al 84,4%) y en incontinencia urinaria (del 66,2 al 73,1%). Descendio la adecuacion en cuanto a enfermedad escrotal (del 67,1 al 63,3%) y se mantuvo similar en ITU (en torno al 76%). Conclusiones El trabajo conjunto entre Urologia y Atencion Primaria consigue mejorar la adecuacion de las derivaciones en las enfermedades urologicas mas frecuentes.

Background and objective There are 2 types of amyloidosis caused by transthyretin deposits: the wild type (wt-ATTR) and the mutant type (m-ATTR), transmitted by autosomal dominant inheritance with variable penetrance, manifesting with neurological and/or cardiac symptoms. We report on 3 families affected by m-ATTR diagnosed in a nonendemic area. Material and methods We studied 63 patients with a high suspicion of ATTR. The diagnosis was subsequently performed by magnification through polymerase chain reaction of DNA. For the positive cases, we studied the first-degree relatives. Results We detected 7 positive cases of m-ATTR, distributed among 3 families (Glu74Gln, Val142Ile in heterozygosity and Val142Ile in homozygosity), and 3 cases of nonpathogenic variants. Conclusions Hereditary ATTR is a rare disease but is present in nonendemic areas and should therefore be considered in the differential diagnosis of patients with polyneuropathy and/or heart failure with preserved ejection fraction.

Resumen Antecedente y objetivo Existen 2 tipos de amiloidosis producidas por depositos de transtiretina, el tipo salvaje (wt-ATTR) y el tipo mutante (m-ATTR), transmitido por herencia autosomica dominante con penetrancia variable, manifestandose con clinica neurologica y/o cardiaca. Describimos 3 familias afectadas por m-ATTR diagnosticadas en un area no endemica. Material y metodos Se estudiaron 63 pacientes con alta sospecha de amiloidosis TTR. Posteriormente, el diagnostico se realizo por amplificacion mediante PCR de ADN y en los casos positivos se estudiaron a los familiares de primer grado. Resultados Se detectaron 7 casos positivos para m-ATTR, distribuidos en 3 familias (Glu74Gln, Val142Ile en heterocigosis y Val142Ile en homocigosis) y 3 casos de variantes no patogenicas. Conclusiones La amiloidosis hereditaria por TTR es una enfermedad rara, pero presente en areas no endemicas, por lo que debe tenerse en cuenta en el diagnostico diferencial de los pacientes con polineuropatia y/o insuficiencia cardiaca con fraccion de eyeccion preservada.

A 54-year-old male with a medical history of diabetes mellitus type 2 and tonsil cancer treated with radiochemotherapy years previously was admitted to hospital due to one-month progressive diarrhea, epigastric pain and 14-kg weight loss. Laboratory tests revealed mild anemia (Hb 10.8 g/dl). Upper endoscopy (UE) showed multiple ulcerated lesions with raised edges and a hard consistency on biopsy, being more evident at the duodenum and with a lower frequency and smaller diameter in the stomach.

Intelligent video analysis from sources such as urban surveillance cameras is a prolific research area today. Multiple types of computer architectures offer a wide range of possibilities when addressing the needs of computer vision technologies. When it comes to real time processing for high level and complex event detections, however, some limitations may arise, such as the computing power in the edge or the cost of sending real time video to the cloud for running advanced algorithms. In this paper, we present a functional architecture of a complete video surveillance solution and we focus on the metadata-processing event engine which takes care of the high-level video processing that is decoupled from a low-level video analysis. The low-level video analysis running in the edge generates and publishes a flow of JSON messages structure containing the details of bounding boxes detected in each frame into an asynchronous messaging service. The metadata event engine is running in a remote cloud, far from the camera locations. We present the performance evaluation of this event engine under different circumstances simulating data coming simultaneously from multiple cameras, in order to study the best strategies when deploying and partitioning distributed processing tasks.

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients.Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization.Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39–1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360–842] vs. 870 mg [IQR 364–1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00–17.5] vs. 18.5 days [3.00–53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05–2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC.Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19.Clinical Trial Registration: Identifier [NCT04341038/EudraCT: 2020-001445-39].

Background We present the use of intravascular lithotripsy as a treatment for highly calcified superior mesenteric artery stenosis. Case presentation A 67-year-old diabetic man had chronic postprandial abdominal pain and weight loss. Computed tomography angiography revealed highly calcified stenosis of the superior mesenteric artery. Selective angiography confirmed severe stenosis. A Shockwave lithotripsy balloon catheter was successfully used via brachial access to modify calcified plaque and increase vascular lumen. After 12 months of follow-up the patient had gained weight and had no abdominal postprandial pain. Conclusion Intravascular lithotripsy could be considered a new treatment modality to modify calcified lesions in the visceral arteries. More controlled studies are needed to demonstrate the efficacy, safety and feasibility of this new technology. Level of evidence 4, Case Report

The aim of this study was to use data from the United Nations Global Indicators Database to analyze the trends in the HIV incidence rate among women in sub-Saharan African countries between 2000 and 2017. The HIV incidence rate is defined as the number of new HIV infections per 1,000 uninfected population, aged 15 to 49 years old. Joinpoint regression analysis was applied to identify periods when there were significant changes in the HIV incidence rate. The results show that there was a global decrease trend in the HIV incidence rates among women in sub-Saharan Africa, decreasing in all sub-Saharan African countries, except in Angola, Equatorial Guinea, and Sudan, which have remained the same, and Madagascar, where the overall trend is increasing. The joinpoint regression statistical method offers an in-depth analysis of the incidence of HIV among women in sub-Saharan Africa.

Background Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. Methods PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph’s Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True–false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. Results One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. Conclusion There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

The non-Hermitian nature of confined photonic modes is described by the electric complex modal volume, VE, which represents a key parameter that leads to counterintuitive effects, such as negative modal contribution to the local density of states and non-Lorentzian lineshapes. Here, we address the magnetic counterpart of VE by means of near-field perturbation experiments in a photonic crystal slab cavity. We study the relevant role played by the imaginary part of the magnetic modal volume, VH, which can increase the quality factor of the confined modes by means of a local external magnetic perturbation. We show how a mapping of the spatial distribution of both the real and imaginary parts of VH can be inferred by near-field experiments employing Al-covered near-field tips. Our findings deepen the role of the magnetic component of light and could open a new route in employing metamaterials, magnetic quantum emitters, and topological photonics., P.L. acknowledges NOMOS (ANR-18CE24-0026) and I-SQUAD (ANR-18CE47-0006) Projects for financial support. M.G. acknowledges funding from CdR Firenze (2018/24257).

The color stability of interim computer-aided design and computer-assisted manufacturing (CAD/CAM) materials has not been exhaustively investigated. The aim of this study was to compare the translucency (TP) and contrast ratio (CR) of CAD/CAM blocks and conventional interim materials, as well as the effects of varnish application and tooth-brushing on color stability after immersion in different staining solutions. Four hundred and eighty specimens were fabricated with four different interim materials (n = 120) and were divided into three experimental, and one control group (n = 30). The color measurements were taken at the initial time (T0), 24 h (T1), 7 days (T2), and 30 days (T3) after immersion in different solutions. CIEDE2000 (ΔE00) values were analyzed with ANOVA and Fischer’s LSD test with a 95% confidence interval. The relationship between TP and CR was analyzed with a Pearson correlation. All interim materials showed a significant difference (p < 0.05) in color change after 30 days. Results showed that polyethyl methacrylate resins (PEMA) had the highest stability over time. The TP and CR were statistically significant (p < 0.05). It was observed that brushing improved the color stability but the ΔE00 were the highest when the varnish alone or varnish and brushing were used, except in the bis-acryl group, in which varnish and brushing decreased the color stainability.

IntroductionSome COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients.Methods and analysisTACROVID is a randomized, open-label, single-center, phase II trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature ≤ 37.5°C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate ≤24 rpm; for 48 consecutive hours.DiscussionMethylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries.Trial registration numberNCT04341038 / EudraCT: 2020-001445-39