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Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL, Comunidad de Madrid, Grant/Award Number: B2017/BMD-3778; LINFOMAS-CM; Fundación Científica Asociación Española Contra el Cáncer, Grant/Award Number: PROYE18054PIRI; Fundación Ramón Areces, Grant/Award Number: CIVP19S7917; Instituto de Investigación Sanitaria Fundación Jiménez Díaz; Ministerio de Ciencia, Innovación y Universidades, Grant/ Award Number: RTI2018- 093330-B-I00 and MCIU/FEDER; Ministerio de Economía y Competitividad, Grant/Award Number: SAF2015-70561-R and MINECO/FEDER

Smoking remains the leading cause of morbidity and mortality worldwide. Because of its clear influence on cardiovascular and respiratory diseases, it is an important factor in internal medicine consultations. Although the rate of smoking cessation has been increasing in recent years, there is a percentage of patients who continue to smoke because they are unable or unwilling to quit, despite having tried existing pharmacological and non-pharmacological therapies. For this group of patients there are strategies based on interventions aimed at reducing the negative effects of smoking without the need for complete cessation. In this review it is shown that due to the absence of combustion of organic matter in conventional cigarettes, snus, e-cigarettes and heated tobacco products generate significantly lower levels of toxic substances.

Von Willebrand factor (VWF) is classically associated with primary hemostasis and platelet-rich arterial thromboses, but recently has also been implicated in fibrin clotting and venous thrombosis. Direct interaction between fibrin and VWF may mediate these processes, although prior reports are conflicting.We combined two complementary platforms to characterize VWF-fibrin(ogen) interactions and identify their potential physiologic significance.Engineered microvessels were lined with human endothelial cells, cultured under flow, and activated to release VWF and form transluminal VWF fibers. Fibrinogen, fibrin monomers, or polymerizing fibrin were then perfused, and interactions with VWF evaluated. Thrombin and fibrinogen were perfused into living versus paraformeldahyde-fixed microvessels and the pressure drop across microvessels monitored. Separately, protein binding to tethered VWF was assessed on a single-molecule level using total internal reflection fluorescence (TIRF) microscopy.Within microvessels, VWF fibers colocalized with polymerizing fibrin, but not fibrinogen. TIRF microscopy showed no colocalization between VWF and fibrinogen or fibrin monomers in a microfluidic flow chamber across a range of shear rates and protein concentrations. Thrombin-mediated fibrin polymerization within living microvessels triggered endothelial VWF release, increasing the rate and amount of microvessel obstruction compared to fixed vessels with an inert endothelium.We did not identify specific binding between fibrin(ogen) and VWF at a single-molecule level. Despite this, our results suggest that rapid release of endothelial VWF during clotting may provide a physical support for fibrin polymerization and accelerate thrombosis. This interaction may be of fundamental importance for the understanding and treatment of human thrombotic disease.

Statement of problem In spite of a digital workflow playing an important role in the intraoral prosthetic rehabilitation of patients with head and neck cancer, information about how it has been implemented and its clinical implications is sparse. Purpose The purpose of this systematic review was to evaluate the use of a digital workflow in the intraoral prosthetic rehabilitation of patients with head and neck cancer by analyzing the frequency and type of the digital procedures used. Material and methods Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The following terms were applied for the search conducted in the MEDLINE-PubMed, Cochrane, and SciELO databases: (prosthesis OR dental OR rehabilitation) AND (digital OR CAD-CAM OR intraoral scanner) AND (Cancer OR head neck). Articles that specified data on intraoral prosthetic treatment and analyzed the use of a digital workflow in the different prosthetic phases such as digital scanning and computer-aided design and computer-aided manufacturing (CAD-CAM) in patients with head and neck cancer were included. Data from the frequency and type of digital procedures were analyzed. Results Thirteen articles were included, and all had incorporated CAD-CAM techniques in at least 1 of the prosthetic treatment stages (scanning, design, and/or fabrication). Only 1 patient was rehabilitated by using a completely digital workflow. The most frequent prosthetic treatment was an obturator (82.6%). Regarding the image capture method, the most used method was cone beam computed tomography (CBCT) (60.9%). Conclusions Most reports described the partial use of a digital workflow in the intraoral prosthetic rehabilitation of patients treated for head and neck cancer. A digital workflow is used for specific stages but not for the entire process. More studies are needed to evaluate digital systems, ideally comparing parameters with the conventional method, and to determine whether this technique has more relevant clinical implications.

Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles, and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion-transmitted infections), or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology characterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.La hemofilia es un trastorno hemorrágico con patrón de herencia ligado al sexo, caracterizado por una incapacidad en la amplificación de la coagulación ocasionada por la deficiencia del factor VIII (hemofilia A o clásica) o del factor IX (hemofilia B). La secuenciación de los genes involucrados en la hemofilia ha permitido la descripción y registro de las principales mutaciones, así como la correlación con los diversos grados de severidad. Las manifestaciones hemorrágicas se relacionan con los niveles de factor deficiente circulante, afectando principalmente al sistema musculoesquelético y en particular a las grandes articulaciones (rodillas, tobillos y codos). El presente documento hace una revisión y consenso de los principales aspectos genéticos de la hemofilia, desde el patrón de herencia y el concepto de mujeres portadoras, la fisiopatología y clasificación de la enfermedad, los estudios básicos y de confirmación ante la sospecha de hemofilia, y de los diversos esquemas de tratamiento basados en la infusión del factor de coagulación deficiente hasta las terapias innovadoras libres de factor, así como de las recomendaciones para el manejo de las complicaciones asociadas al tratamiento (desarrollo de inhibidores y/o infecciones transmitidas por transfusión) o secundarias a los eventos hemorrágicos a nivel articular (artropatía hemofílica). La parte final del documento revisa los aspectos clínicos y de tratamiento relevantes de una patología hemorragica caracterizada por la deficiencia adquirida del FVIII mediada por anticuerpos neutralizantes denominada hemofilia adquirida.

Hereditary haemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu Syndrome) is an inherited vascular disorder, associated with arteriovenous malformations and bleeding events. Despite potential benefits, data regarding the use of left atrial appendage occlusion (LAAO) in HHT patients with non-valvular atrial fibrillation (NVAF) is scarce. The aim of the present paper was to assess the outcomes of HHT patients undergoing LAAO.This multicentre observational study included all consecutive patients with NVAF and a previous diagnosis of HHT who underwent LAAO between 2015 and December 2020. The follow-up protocol included a clinical control at 3 months after hospital discharge, and then yearly.Overall, 822 subjects undergoing LAAO were initially screened for the study. Among them, 7 patients had previous diagnosis of HHT. Device implant success was achieved in all patients and non-procedural adverse event were observed. At the maximum follow-up (median follow up = 470.5 days), no ischemic strokes or device related thrombosis (DRT) were reported. Absence of antithrombotic treatment after LAAO was not associated with an increased risk of stroke or DRT.LAAO might represent a promising non-pharmacological alternative to prevent thromboembolic events in patients with HHT and NVAF.

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p

The incidence of myocarditis after RNA-based vaccines for coronavirus has gained social and medical interest.We performed an intention-to-treat meta-analysis, following the PRISMA statement. After a systematic search, without language restriction, 9 publications were selected. Two were excluded (one was only in subjects with age 12-17 and other might had included subjects from a larger publication). We followed the PRISMA guidelines for abstracting data and assessing data quality and validity. Data was verified by 2 investigators.We analyzed 17,704,413 subjects, from 7 studies, that included 627 cases of confirmed myocarditis). The incidence of myocarditis was 0.0035% (95% CI 0.0034-0.0035). Mean incidence rate was 10.69 per 100.000 persons-year. Cases reported from Israel represented 45.14% from total (283 out of the 627). Only 1 case of fatal myocarditis or death was reported. There was significant heterogeneity between results. The meta-regression analysis excluded mean age, region, number of cases or number of people included as sources of heterogeneity. No small-study effect was observed (p = 0.19).Myocarditis incidence after RNA vaccines is very rare (0.0035%) and has a very favorable clinical course.

Pertussis is a highly contagious, vaccine-preventable respiratory tract infection, with high morbidity and mortality and a particularly severe effect on newborns and infants under 2 months. The first pertussis vaccines were introduced in the 1940s. Since 1980, however, the incidence of cases has risen despite the extensive vaccination programmes and antibiotic adjuvant treatments available. Transition from the use of whole-cell vaccines to acellular vaccines and the antigenic modifications of Bordetella pertussis have contributed, among other factors, to a reduction in vaccine-acquired immunity and reemergence of the disease. Today, there are still unmet needs not covered by conventional prevention measures and existing antibiotic treatments. This review aims to update the available data, and to discuss which vaccine strategies might contribute to better disease control and prevention.

Ewing sarcoma (ES) is an aggressive neoplasm with variable morphology. It has no specific immunoprofile or molecular signature. Neither CD99, NKX2.2 nor PAX7 immunoreactivity alone is completely specific, although diagnostic specificity improves when combined. The purpose of the present study was to investigate the immunohistochemical (IHC) expression of PAX7 in a large series of genetically confirmed ES. Existing results for CD99 and NKX2.2 immunoexpression, morphological findings and molecular studies (fusion gene subtypes) were retrieved from a previous study. Survival analyses were performed in cases with available clinical follow-up. PAX7 was positive in 95.5% of ES with diffuse staining ( 50%) in all positive cases and moderate or strong intensity for most cases. Nineteen ES displayed both PAX7 and CD99 immunoreactivity but lacked NKX2.2 immunoexpression. No relationships could be found between PAX7 expression and the histological types or ES gene fusion subtypes. Univariant/multivariate analysis showed that lack of PAX7 and/or NKX2.2 immunoexpression constitute independent poor prognostic factors for progression free survival (PFS) and overall survival (OS). In conclusion, IHC for CD99, NKX2.2, and PAX7 may be useful in daily practice for ES diagnosis, particularly in hospitals lacking facilities for molecular studies. In addition, the combination of strong CD99 membranous positivity and nuclear PAX7 and NKX2.2 immunoreactivity seems to be very reliable for ES diagnosis when supported by a corroborating histomorphologic and clinical picture. Although PAX7 is not entirely specific for ES, it seems to have a more extensive and strong nuclear immunoreactivity than NKX2.2 expression, even in tumors with decalcification artifact. Considering the prognostically significant data herein reported, we strongly recommend validation in prospective ES series that include localized and disseminated tumors.

The food industry is constantly attempting to develop better products that will have a positive effect on health. Feiraco® and Clesa®, expressed their intention to create novel products using UNICLA® milk as a matrix to develop functional foods. In this respect, β-cyclodextrin (β-CD) at 1% was able to reduce the cholesterol concentration in Feiraco-UNICLA® milk products by around 87-85%. Products were fortified with omega-3 from fish oil with α- and β-CD acting as carriers. It was possible to add around 50% of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) Recommended Dietary Allowances (RDA), with a high diet proportion of fibre and similar organoleptic properties to commercial omega-3 products. 80% of a sensory panel found our formulations satisfactory. The final product was stable, and the bioaccessibilty of the fatty acids added to the milk was around 74%. These results as a whole satisfy the aid of Feiraco® and Clesa® to develop improved products.

Emerging infectious diseases are one of the most important global health challenges because of their impact on human and animal health. The vector-borne West Nile virus (WNV) is transmitted between birds by mosquitos, but it can also infect humans and horses causing disease. The local circulation of WNV in Spain has been known for decades, and since 2010, there have been regular outbreaks in horses, although only six cases were reported in humans until 2019. In 2020, Spain experienced a major outbreak with 77 human cases, which was followed by 6 additional cases in 2021, most of them in the Andalusian region (southern Spain). This study aimed to characterize the genomes of the WNV circulating in wild-trapped mosquitoes during 2020 and 2021 in Andalusia. We sequenced the WNV consensus genome from two mosquito pools and carried out the phylogenetic analyses. We also compared the obtained genomes with those sequenced from human samples obtained during the outbreak and the genomes obtained previously in Spain from birds (2007 and 2017), mosquitoes (2008) and horses (2010) to better understand the eco-epidemiology of WNV in Spain. As expected, the WNV genomes recovered from mosquito pools in 2020 were closely related to those recovered from humans of the same outbreak. In addition, the strain of WNV circulating in 2021 was highly related to the WNV strain that caused the 2020 outbreak, suggesting that WNV is overwintering in the area. Consequently, future outbreaks of the same strain may occur in in the future., This research was funded by the Research State Agency projects PGC2018-095704-B-I00 and PID2020-118921RJ-I00, Instituto de Salud Carlos III Project PI19CIII_00014, European Commission—NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global+).

The aim of this study was to analyze current data on the population's level of knowledge about COPD and to evaluate certain diagnostic interventions, such as the use of spirometry.An epidemiological, observational, cross-sectional study by telephone interview, with random dialing of landline telephone numbers, was conducted in November 2019, in a nationally representative sample of adults over 40 years of age.From a total of 51,079 telephone calls, a total of 1920 individuals responded. Mean age was 61.9 years and 31.6% were men. Overall, 19.4% were current smokers and 13.4% reported respiratory disease (5% reported COPD). In total, 27.9% had spontaneous knowledge of COPD, which is a relative increase from the 17% observed in 2011. The most frequent information channel was the media (35.5%), with a significant presence of social networks and the Internet (25.7%). Almost one fifth (18.1%) had chronic respiratory symptoms. Of these, 59.3% had requested medical care, and 66.2% had undergone spirometry. Spirometry was performed less frequently in subjects treated in primary care compared to respiratory medicine departments (51.9% versus 79.1%; P .001).Knowledge of COPD is still scarce, and strategies are needed to increase awareness and the importance of assessing respiratory symptoms and increased use of spirometry.

Preeclampsia, a pregnancy-related endothelial disorder, is associated with both cardiovascular and cerebrovascular complications. Preeclampsia requires the presence of a placenta as part of its pathophysiology, yet the role of this organ in the cerebrovascular complications remains unclear. Research has shown that circulating small extracellular vesicles (also known as exosomes) present in preeclampsia plasma can generate endothelial dysfunction, but it is unclear whether the impairment of function of brain endothelial cells at the blood-brain barrier is secondary to plasma-derived or placental-derived exosomes. In this study, we evaluated the effect of small extracellular vesicles isolated from plasma samples of women with preeclampsia (n=12) and women with normal pregnancy (n=11) as well as from human placental explants from normotensive pregnancies (n=6) subjected to hypoxia (1% oxygen) on the integrity of the blood-brain barrier, using both in vitro and animal models. Exposure of human-derived brain endothelial cell monolayers to plasma and plasma-derived small extracellular vesicles from preeclamptic pregnancies increased the permeability and reduced the transendothelial electrical resistance. A similar outcome was observed with hypoxic placental-derived small extracellular vesicles, which also increased the permeability to Evan’s blue in the brain of C57BL6 nonpregnant mice. Cotreatment with magnesium sulfate reversed the effects elicited by plasma, plasma-derived, and hypoxic placental-derived small extracellular vesicles in the employed models. Thus, circulating small extracellular vesicles in plasma from women with preeclampsia or from hypoxic placentae disrupt the blood-brain barrier, which can be prevented using magnesium sulfate. These findings provide new insights into the pathophysiology of cerebral complications associated with preeclampsia.

Background The efficacy of mouth-rinses strongly depends upon their substantivity. The use of natural and non-toxic products that avoid secondary effects is gaining interest in preventive dentistry. The purpose of this study was to evaluate the substantivity of two formulations of mouth-washing solutions based on cetylpyridinium (CPC) and O-cymen-5-ol. Methods This was a randomized, double-blind, crossover trial conducted at the Faculty of Medicine and Health Sciences of the University of Barcelona. Bacterial re-colonization was followed by live/dead (SYTOTM9 + propidium iodide) bacterial staining and measured by confocal laser scanning microscopy and fluorometry. Unstimulated saliva samples were collected from 16 healthy individuals at baseline saliva and then, at 15 min, 30 min and 1, 2, 3, and 4 h after the following mouth-rinses: (i) a single, 1-min mouth-rinse with 15 ml of placebo (negative control); (ii) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) ; (iii) a single, 1-min mouth-rinse with 15 ml of O-cymen-5-ol (0.09%); (iv) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) + O-cymen-5-ol (0.09%). Results Proportion of dead bacteria was significantly higher for all mouthrinses during the first 15 min compared to baseline (CPC = 48.0 ± 13.9; 95% CI 40.98–56.99; p p p p p p p p Conclusion The synergistic interaction of CPC and O-cymen-5-ol prolongs their substantivity. The resulting formulation may be as effective as other antimicrobials, such as triclosan or chlorhexidine, but without their undesirable secondary effects. Thus, mouthrinsing products based on Combinations of CPC and O-cymen-5-ol may replace in the near future Triclosan and Chlorhexidine—based mouthrinses.

Background This study investigated the association between xerostomia and health risk behaviours, general and oral health and quality of life. Methods A cross-sectional study involving 800 adults over 65 years of age residing in Spain using a computer-assisted telephone questionnaire. The severity of xerostomia was assessed through the Xerostomia Inventory (XI). Both univariate and adjusted multinomial logistic regression were used to determine the risk (OR) of xerostomia. Results The sample comprised of 492 females (61.5%) and 308 males, with a mean age of 73.7 ± 5.8 years. Some, 30.7% had xerostomia: 25.6% mild, 4.8% moderate and 0.3% severe, the majority being female (34.8% vs 24%; p = 0.003). The mean XI was 24.6 ± 6.3 (95% CI 19.2–24.8) for those with poor health, whereas it was 17.4 ± 6.3 (95%CI 16.1–18.6) in those reporting very good health (p p = 0.002). Logistic regression showed that the highest OR for xerostomia was observed among adults with poor general health (2.81; 95%CI 1.8–4.3; p p = 0.001). Those who needed help with household chores had 2.16 higher OR (95%CI 1.4–3.4; p = 0.001) and 1.69 (95%CI 1.1–2.7; p = 0.03) in the adjusted model. Females had a higher risk of suffering from xerostomia than males. Conclusion The strong association between xerostomia and the general and oral health status of older adults justifies the need for early assessment and regular follow-up.

Trial registration www. clini caltr ials. gov (ID: NCT04180319), Background Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function., Grifols, CSL Behring, Kamada, pH Pharma, Takeda to the European Respiratory Society (ERS).

Background: Previous studies regarding antioxidant consumption and glaucoma have shown contradictory results. The aim of this study was to analyze the combined effect of the consumption of three vitamins (A, C and E) on the incidence of glaucoma in the SUN Project. Methods: For this study, 18,669 participants were included. The mean follow-up was 11.5 years. An index including vitamins A, C and E (ACE-Vitamin Index) was calculated. Vitamin intake was extracted from participants’ dietary data and vitamin supplements, if taken. Information on glaucoma incidence was collected by previously validated self-reported questionnaires. The association between glaucoma and vitamin intake was assessed by repeated-measures Cox regression using multi-adjusted hazard ratios. Results: A total of 251 (1.3%) cases of glaucoma were detected. Participants with a higher ACE-Vitamin Index presented a reduced risk of glaucoma compared to participants with lower consumption (adjusted HR = 0.73; 95% CI, (0.55–0.98)). When each vitamin was analyzed individually, none of them had a significant protective effect. The protective effect of the ACE-Vitamin Index was higher in men and older participants (≥55 year). Conclusions: The consumption of vitamins A, C and E considered separately do not seem to exert a protective effect against glaucoma, but when these vitamins are considered together, they are associated with a lower risk of glaucoma.

Cognitive multisensory rehabilitation (CMR) -a therapeutic approach to help recover movement using neurocognitive exercises- activates patient's perceptive and cognitive processes, key for motor learning. The aim of this systematic review was to assess the effectiveness of CMR on motor function and quality of life and compare the findings with other rehabilitation approaches or no-intervention in neurological and trauma adult and pediatric patients. We carried out a systematic review of randomized controlled clinical trials, pilot studies, and case series in PubMed, PEDro, Cochrane Library, and the CINHAL Complete database published between 2012 and 2021. Ten studies met the eligibility criteria. CMR provides similar or superior benefits compared to other types of approaches for the restoration of upper limb function, gait, balance, and quality of life in neurological and trauma patients. Further research with larger samples and higher methodological quality need to be developed to de-termine its long-term effectiveness.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that, occasionally, may spread to the central nervous system (CNS), being the most common cause of sporadic encephalitis. One of the main neurovirulence factors of HSV-1 is the protein ICP34.5 that, although initially seemed to be relevant only in neuronal infections, it can also promote viral replication in non-neuronal cells. New ICP34.5 functions have been discovered during the recent years, and some of them have been questioned. This review describes the mechanisms of ICP34.5 to control cellular antiviral responses and debates its most controversial functions. One of the most discussed roles of ICP34.5 is autophagy inhibition. Although autophagy is considered a defense mechanism against viral infections, current evidence suggests that this antiviral function is only one side of the coin. Different types of autophagic pathways interact with HSV-1 impairing or enhancing the infection, and both the virus and the host cell modulate these pathways to tip the scales in its favor. In this review, we will summarize the recent progress on the interplay between autophagy and HSV-1, focusing on the intricate role of ICP34.5 in the modulation of this pathway to gain the battle against cellular defenses.

Growth alterations have been described in patients operated on for oral clefts. The purpose of this work was to analyze the craniofacial and palate morphology and dimensions of young adults operated on for oral clefts in early childhood in Spain. Eighty-three patients from eight different hospitals were divided into four groups based on their type of cleft: cleft lip (CL, n = 6), unilateral cleft lip and palate (UCLP, n = 37), bilateral cleft lip and palate (BCLP, n = 16), and cleft palate only (CPO, n = 24). A control group was formed of 71 individuals. Three-dimensional (3D) digital models were obtained from all groups with an intraoral scanner, together with cephalometries and frontal, lateral, and submental facial photographs. Measurements were obtained and analyzed statistically. Our results showed craniofacial alterations in the BCLP, UCLP, and CPO groups with an influence on the palate, maxilla, and mandible and a direct impact on facial appearance. This effect was more severe in the BCLP group. Measurements in the CL group were similar to those in the control group. Cleft characteristics and cleft type seem to be the main determining factors of long-term craniofacial growth alterations in these patients. Prospective research is needed to clearly delineate the effects of different treatments on the craniofacial appearance of adult cleft patients.

Background: the assessment of diet quality (DQ) is fundamental to the study of disease-diet associations, and it is necesary to implement an easy to-apply tool in nursing homes (NHs). Our objective was to propose and apply a novel diet quality indicator (DQIn) using an a priori approach for NHs. Methods: the QUality Index for Nutrition in Nursing homes (QUINN) was implemented in a public NH located in Valladolid, Spain, during a 5-week period (n = 137 subjects). The choice of the QUINN components was based on a rapid review. The QUINN was based on 15 dietary components - 12 were basic (vegetables, fruits, legumes, olive oil, cereals, dairy, white fish and seafood, white-meat, eggs/positive; other fats, red and processed meat, and sweets/negative), and 3 were supplementary (fruits and vegetables variety, oily-fish, and whole-grains/positive). Each component was classified into 4-categories (0, 1, 2 o 3 points; range: 0-45 points). Results: the QUINN was tested on a menu offered by a NH giving a result of 34 points (good diet). The components with the highest scores were related to the Mediterranean diet (high consumption of legumes, olive oil, white fish and shellfish; low intake of other fats; and a wide variety of fruits and vegetables), together with cereals, white meat, dairy, and eggs. The components that required a major change were red- and processed-meats, sweets, and whole grains. Conclusion: the menu of this Spanish NH showed a good DQ according to the QUINN. The assessment of the DQ in NHs using QUINN will allow the proposal of interventions aimed at improving their diet.Antecedentes: la valoración de la calidad de la dieta es fundamental para el estudio de las asociaciones enfermedad-dieta, y es necesario implantar una herramienta de fácil aplicación en las residencias de ancianos. Nuestro objetivo fue proponer y aplicar un nuevo indicador de calidad de la dieta (diet quality indicator, DQIn) utilizando un enfoque a priori para su utilización en residencias de ancianos. Métodos: el Índice de Calidad Nutricional en Residencias de Ancianos (QUality Index for Nutrition in Nursing homes, QUINN) se aplicó en una residencia pública de Valladolid durante un periodo de 5 semanas (n = 137 sujetos). La elección de los componentes del QUINN se basó en una revisión rápida. En el QUINN se consideraron 15 componentes dietéticos, 12 básicos (verduras, frutas, legumbres, aceite de oliva, cereales, lácteos, pescado blanco y marisco, carnes blancas, huevos/positivos; otras grasas, carnes rojas y procesadas, y dulces/negativos) y 3 adicionales (variedad de frutas y verduras, pescado azul, y cereales integrales/positivos). Cada componente se clasificó en 4 categorías (0, 1, 2 o 3 puntos; rango: 0-45 puntos). Resultados: el QUINN se aplicó en el menú ofertado por una residencia de ancianos dando un resultado de 34 puntos (dieta de buena calidad). Los componentes con mayor puntuación estaban relacionados con la dieta mediterránea (alto consumo de legumbres, aceite de oliva, pescado blanco y marisco, bajo consumo de otras grasas y variedad de frutas y verduras), junto con los cereales, las carnes blancas, los lácteos y los huevos. Los componentes que requerían un cambio importante fueron las carnes rojas y procesadas, los dulces y los cereales integrales. Conclusión: el menú de esta residencia de ancianos situada en España mostró una calidad de la dieta buena según el QUINN. La evaluación de la calidad de la dieta en las residencias de ancianos mediante el QUINN permitirá proponer intervenciones para mejorar la dieta.

The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P

Background Breast cancer survivors (BCS) face several symptoms and are at higher risk of weight gain following diagnosis. Current literature shows that both exercise and diet play a key role in recovery of BCS. However, there is a gap between current guidelines and the real-world context. The aim of this article is to describe the process behind a free, not-for-profit community-based therapeutic exercise and education programme (TEEP) for BCS in the clinical setting. Methods The “Onco-Health Club” (OHC) consists of therapeutic exercise (TE) intervention aimed at ameliorating cancer-related fatigue (CRF) and improving QoL and physical function. TE is supplemented with nutritional education, providing information about the Mediterranean diet. To this end, patients are recruited from an oncologist and are referred to a physiotherapist and a nutritionist for baseline assessment. TEEP consists of a 3-month intervention, delivered twice a week in a group format with 1 h of TE and 30 min of nutritional education. BCS then have a final assessment and are advised to continue with a healthy lifestyle. Data about referral, compliance and assessment were collected. Results From May 2017 to February of 2020, a total of 158 patients were recruited from 8 cohorts and 142 initially started the OHC. From 119 that joined the program, 96 patients were considered to have finished it with good adherence (assistance > 80%). BCS significantly improved their QoL, as well as upper and lower limb’s function, and increased their level of physical activity. CRF tended to decrease (p = 0.005). Conclusions This study obtained data on recruitment, compliance, and possible limitations of these kinds of programmes in a real-world context. Further research is needed in order to optimize patient engagement and compliance, as well as to determine the transferability of these programmes in the clinical setting. Trial registration NCT03879096, Registered 18th March 2019. Retrospectively registered.

11 pags., 6 figs., 5 tabs., Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3 - also named eosinophil cationic protein - by non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages., This work was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades: SAF2015-72518-EXP, SAF2017- ́ 82158-R and RYC-2012-09999 to M.T.; CTQ2017-84371-P to M.A.J.; AGL2014-52395-C2; AGL2017-84097-C2-2-R to D.A. and PID2019-106123GB-I00 to E.B. Additional financial support from the European Society for Clinical Microbiology and Infectious Disease, ESCMID 2016, to M.T., the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya, 2019 LLAV 00029 to M.T. and 2016 PROD 00060 to E.B. The “Marí a de Maeztu” Program for Units of Excellence in R&D from the Spanish Ministry of Innovation and Competitiveness (MINECO) for work at Pompeu Fabra University (D.A.) is acknowledged. This work was supported, in part, by the European Regional Development Fund ‘A Way to Achieve Europe’ [Spanish Network for Research in Infectious Diseases (Grant No. RD16/0016/0003)]. D.S. and B.C.-A. are recipients of pre-doctoral FPI scholarships (PRE2018-083243 and BES-2015-073383, respectively) from the Spanish Ministerio de Ciencia, Innovacion y Universidades.

Diagnosis of non-facial melanomas on sun-damaged skin or extrafacial lentigo maligna is challenging.To identify the evolutionary dermoscopic signs, characteristic of this type of non-facial melanoma on sun-damaged skin.This retrospective descriptive observational study included 90 dermoscopic follow-up images of 22 non-facial melanomas on sun-damaged skin from 17 high-risk melanoma patients, followed with digital dermoscopy and diagnosed between January 2016 and October 2020. We recorded dermoscopic changes by comparing each dermoscopic image with the previous one (mean dermoscopic follow-up of the excised lesions was 3.6 years). Confocal microscopy images were taken at diagnosis.In total, 51.5% (95% CI: 39-64) showed an appearance or increase in featureless areas with surrounding small round or triangular dark brown-blue structures, 23% (95% CI: 23-46) showed an increase in other geometric structures (angulated lines, zig-zag lines and polycyclic structures), 5.9% (95% CI: 2-14) showed an appearance or increase in bright white lines and atypical vascularization, 26.5% (95% CI: 17-39) showed an appearance or increase in follicular pigmentation structures or follicular radial lines, and 39.7% (95% CI: 28-52) showed focal islands of pigmentation in these areas. Of the changes, 54% occurred at the last and diagnostic visit. There was an increase in size in only 20.6% (95% CI: 12-32). Also, 81.8% showed pagetoid cells in the epidermis, 95.5% atypical cells at the dermoepidermal junction by reflectance confocal microscopy, and 95.5% showed non-edged or edged and non-edged papillae.This study identifies the dermoscopic evolutionary changes associated with extrafacial lentigo maligna.

Background: The 24-h movement guidelines for youth and adults recommend the specific duration of physical activity, sedentary time, and sleep duration to ensure optimal health, but little is known about its relationship to mental health indicators. The aim of the study was to explore the association between 24-h movement guidelines in adolescence and its trajectories from middle adolescence (12–17 years old) to adulthood (33–39 years old) with depression and suicidal ideation in adulthood. Methods: This prospective cohort study included individuals who participated in Waves I (1994–1995) and V (2016–2018) of the National Longitudinal Study of Adolescent Health (Add Health) in the United States. Physical activity, screen time and sleep duration were measured using questionnaires. Adults were categorized as having depression if they had a self-reported history of depression and/or prescription medication-use for depression in the previous four weeks. Suicidal ideation was assessed by a self-reported single question in both waves. Poisson regression analyses were used to estimate the incidence rate ratio (IRR) of depression and suicidal ideation at adulthood, according to meeting specific and combinations of 24-h movement guidelines at Wave I and its trajectories from adolescence to adulthood. Results: The study included 7,069 individuals (56.8% women). Adolescents who met physical activity guidelines and all three guidelines at middle adolescence had lower risk of depression (IRR = 0.84, 95%CI 0.72 to 0.98) and suicidal ideation (IRR = 0.74, 95%CI 0.55 to 0.99) at adulthood than those who did not meet any of these guidelines, respectively. Individuals who met the guidelines for screen time and all three guidelines in both adolescence and adulthood had lower risk of depression (screen time, IRR = 0.87, 95% CI 0.72 to 0.98; all three, IRR = 0.37, 95% CI 0.15 to 0.92) and suicidal ideation (screen time, IRR = 0.74, 95% CI 0.51 to 0.97; all three, IRR = 0.12, 95% CI 0.06 to 0.33) than those who never met the guidelines. Additionally, individuals who did not meet all three guidelines in adolescence but met the guidelines in adulthood had lower risk of suicidal ideation than those who never met the guidelines (IRR = 0.81, 95%CI 0.45 to 0.89). Conclusion: Our findings highlight the importance of promoting and maintaining adherence to the 24-h movement guidelines from middle adolescence to adulthood to prevent mental health problems. However, our findings must be interpreted carefully due to declared limitations, e.g., the self-reported assessments which are subject to sources of error and bias or that the dataset used to gauge meeting a guidelines (1994–1996) was made later (2016).

Reports of West Nile virus (WNV) associated disease in humans were scarce in Spain until summer 2020, when 77 cases were reported, eight fatal. Most cases occurred next to the Guadalquivir River in the Sevillian villages of Puebla del Río and Coria del Río. Detection of WNV disease in humans was preceded by a large increase in the abundance of Culex perexiguus in the neighborhood of the villages where most human cases occurred. The first WNV infected mosquitoes were captured approximately one month before the detection of the first human cases. Overall, 33 positive pools of Cx. perexiguus and one pool of Culex pipiens were found. Serology of wild birds confirmed WNV circulation inside the affected villages, that transmission to humans also occurred in urban settings and suggests that virus circulation was geographically more widespread than disease cases in humans or horses may indicate. A high prevalence of antibodies was detected in blackbirds (Turdus merula) suggesting that this species played an important role in the amplification of WNV in urban areas. Culex perexiguus was the main vector of WNV among birds in natural and agricultural areas, while its role in urban areas needs to be investigated in more detail. Culex pipiens may have played some role as bridge vector of WNV between birds and humans once the enzootic transmission cycle driven by Cx. perexiguus occurred inside the villages. Surveillance of virus in mosquitoes has the potential to detect WNV well in advance of the first human cases., m CSIC under grant number 202030E263, Research State Agency under grant numbers PGC2018-095704-B-I00 and PID2020-116768RR-C21/C22 FEDER, European Commission – NextGenerationEU (Regulation EU 2020/2094), Instituto de Salud Carlos III Project “PI19CIII_00014”

Lung cancer cells; Cytotoxicity Cèl·lules canceroses de pulmó; Citotoxicitat Células cancerosas de pulmón; Citotoxicidad Lung cancer remains the leading cause of cancer-related death worldwide. We identify DSTYK, a dual serine/threonine and tyrosine non-receptor protein kinase, as a novel actionable target altered in non-small cell lung cancer (NSCLC). We also show DSTYK's association with a lower overall survival (OS) and poorer progression-free survival (PFS) in multiple patient cohorts. Abrogation of DSTYK in lung cancer experimental systems prevents mTOR-dependent cytoprotective autophagy, impairs lysosomal biogenesis and maturation, and induces accumulation of autophagosomes. Moreover, DSTYK inhibition severely affects mitochondrial fitness. We demonstrate in vivo that inhibition of DSTYK sensitizes lung cancer cells to TNF-α-mediated CD8+-killing and immune-resistant lung tumors to anti-PD-1 treatment. Finally, in a series of lung cancer patients, DSTYK copy number gain predicts lack of response to the immunotherapy. In summary, we have uncovered DSTYK as new therapeutic target in lung cancer. Prioritization of this novel target for drug development and clinical testing may expand the percentage of NSCLC patients benefiting from immune-based treatments. This work was supported by Fundación para la investigación médica aplicada (FIMA), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC; CB16/12/00443), Spanish Association Against Cancer Scientific Foundation (AECC; GCB14-2170), Fundación Ramón Areces, Instituto de Salud Carlos III, and co-funded by the European Union (European Regional Development Fund, “A way to make Europe”; PI19/00098; PI19/00230; PI20/00419), Fundación Roberto Arnal Planelles, and International Association for the Study of Lung Cancer (IASLC) Fellowship funding (K. Valencia). M. Echepare was supported by Contratos Predoctorales de Formación en Investigación en Salud (PFIS), Instituto de Salud Carlos III, and co-funded by the European Union (European Social Fund, "Investing in your future"; FI20/00295).

SARS-CoV2 pandemic has altered the normal activity in our day-to-day life. During the most critical moments of the pandemic at the hospital, attendance and programmed activities had to be reduced to a minimum, including kidney transplants. Hospitals with this kind of activity had to suspend or restructure it due to the decrease in the number of donors with a solid organ donation profile, the lack of knowledge as to whether the disease could be transmitted through transplantation or the risk that was believed to be associated with the admission of patients with end-stage chronic kidney disease or immunosuppressive treatment.A retrospective review of all patients who had received a kidney transplant at Doctor Peset University Hospital in Valencia was performed from March 2020 to March 2021. The objective was to study the safety of kidney transplantation and the incidence of COVID-19 disease in kidney transplant patients during this pandemic period.56 cases of kidney transplantation were included, most of them male with an average age of 56 years old, and variable comorbidity such as hypertension, dyslipidemia, an average body mass index of 26 and undergoing renal replacement therapy by hemodialysis. Regarding the organ donors, more than 50% were male patients and the donation was in encephalic death. The average cold ischemia time was 15 hours. Postoperative complications were mostly graded I and II in the Clavien-Dindo classification. 5.4% of the recipients had passed the SARS-CoV2 infection prior to the transplant and 5.4% were infected with COVID-19 after the transplant.In our experience, the current kidney transplant program seems viable and safe, even during periods of health emergencies.

Guselkumab is a monoclonal antibody that selectively blocks the p19 subunit of interleukin 23 and has been approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis in adult patients due to its efficacy in different clinical trials. Therefore, itis important to know the performance of guselkumab in this setting of patients in clinical practice given that a high percentage of them are not represented in these clinical trials. Our objective was to evaluate the effectiveness and tolerability of guselkumab in clinical practice in the first patients with psoriasis and psoriatic arthritis treated since the date of its approval for psoriasis in Spain, in joint dermatology-rheumatology clinics. A multicenter retrospective data collection was carried out, in which 14 hospitals participated, including a total of 90 patients with psoriatic arthritis confirmed by a rheumatologist. Data collection was recorded at baseline and at weeks 12, 24, and 52 for both the articular and cutaneous domains. Ninety PsA patients started treatment with guselkumab and therefore were included in this study. The vast majority had already failed to at least to one biologic therapyprior guselkumab prescription. The median age was 55 years, 61% were female and 46% had a BMI >= 30 kg/m(2). Sixty-nine percent suffered from peripheral arthritis, and in 34% an axial involvement was also detected; dactylitis or enthesitis was present in 24% and 29% of patients, respectively. Guselkumab was effective in controlling both articular and skin manifestations of PsA patients. Absolute PASI significantly decreased from 10.5 to 4.8, 1.9 and 1.3 at weeks 12, 24, and 52, respectively. In 29 out of 61 (48%) of cases, DAPSA was moderate or high, and patients showed a significant reduction in DAPSA at 12, 24, and 52 weeks of treatment (mean DAPSA values at baseline and follow up were 29, 20, 16, and 14, respectively). Patients with DAPSA in low activity or in remission at the time of initiation of guselkumab maintained response at the end of the study period. No new safety concerns were detected. Seventy-eight out of 90 patients (84.4%) persisted on treatment after 2 years follow-up. Our experience suggests that guselkumab isan effective drug for PsA and PsO patients in clinical practice with good tolerability and no additional safety signals, making it a new therapeutic alternative for the treatment of PsA and PsO patients.

Currently, wearable technology is present in different fields that aim to satisfy our needs in daily life, including the improvement of our health in general, the monitoring of patient health, ensuring the safety of people in the workplace or supporting athlete training. The objective of this bibliometric analysis is to examine and map the scientific advances in wearable technologies in healthcare, as well as to identify future challenges within this field and put forward some proposals to address them. In order to achieve this objective, a search of the most recent related literature was carried out in the Scopus database. Our results show that the research can be divided into two periods: before 2013, it focused on design and development of sensors and wearable systems from an engineering perspective and, since 2013, it has focused on the application of this technology to monitoring health and well-being in general, and in alignment with the Sustainable Development Goals wherever feasible. Our results reveal that the United States has been the country with the highest publication rates, with 208 articles (34.7%). The University of California, Los Angeles, is the institution with the most studies on this topic, 19 (3.1%). Sensors journal (Switzerland) is the platform with the most studies on the subject, 51 (8.5%), and has one of the highest citation rates, 1461. We put forward an analysis of keywords and, more specifically, a pennant chart to illustrate the trends in this field of research, prioritizing the area of data collection through wearable sensors, smart clothing and other forms of discrete collection of physiological data.

This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24).

(1) Background. The immediate functional loading of implants is a clinical procedure used for treating periodontal edentulous patients. This clinical study aimed to evaluate the clinical outcomes of the immediate functional loading of implants with fully fixed rehabilitations in compromised periodontal patients. (2) Methods. Three hundred and five implants IPX screw implants were placed in 27 periodontal patients using an immediate functional loading protocol with fixed rehabilitations. All patients had a previous history of periodontitis, four patients (14.8%) were smokers and seven patients (25.9%) suffered from chronic medical conditions. (3) Results. Implant and prosthetic clinical findings were evaluated during a mean period of 41.3 ± 19.6 months. No implants were lost during the clinical follow-up. The cumulative survival rate for all implants was 100%. Regarding the prostheses designed, a total of 54 fixed prostheses were placed in the 27 patients immediately after the surgery. Forty-four hybrid fixed prostheses (81.5%) and 10 fixed rehabilitations (18.5%) were placed in the patients. The mean marginal bone loss was 1.51 ± 1.16 mm, ranging from 0 to 3.5 mm during the follow-up evaluation. Thirty-one implants (10.2%) in 10 patients (37%) were associated with peri-implantitis. Five patients (18.5%) showed some kind of technical complications (loss/fracture of the prosthetic screw, acrylic resin fracture, ceramic chipping). (4) Conclusions. The clinical outcomes of this study demonstrate that fixed rehabilitation by immediate functional loading of implants is considered a predictable procedure.

Background: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children’s and adolescents’ (5–17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. Methods: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders’ top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. Results: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. Conclusions: The Global Matrix 4.0 represents the largest compilation of children’s and adolescents’ PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.

To assess the relationship between particulate matter 2.5 (PM2.5) levels and the prevalence of excess weight in a representative sample of Spanish young people aged 2─14 years.This was an ecological cross-sectional study using data from the 2017 wave of the Encuesta Nacional de Salud Española (ENSE), a nationally representative survey of the Spanish young and adult population. The final sample included 4378 young Spanish people (51.0% boys). The weight (kg) and height (cm) of the study participants were proxy-reported by parents or guardians. Excess weight was determined according to the age- and sex-criteria of the International Obesity Task Force. The PMCompared to young people located in regions with low levels of PMThe prevalence of excess weight in young people was positively associated with PM

Abstract Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC), whose impact can be exacerbated by multidrug-resistant (MDR) strains. Effective control strategies are, therefore, urgently needed. Among them, phage therapy represents a suitable alternative. Here, we describe the isolation and characterization of novel phages from wastewater samples, as well as their lytic activity against biofilm and adherence of UPEC to HEp-2 cells. The results demonstrated that phage vB_EcoM-phiEc1 (ϕEc1) belongs to Myoviridae family, whereas vB_EcoS-phiEc3 (ϕEc3) and vB_EcoS-phiEc4 (ϕEc4) belong to Siphoviridae family. Phages showed lytic activity against UPEC and gut commensal strains. Phage ϕEc1 lysed UPEC serogroups, whereas phages ϕEc3 and ϕEc4 lysed only UTI strains with higher prevalence toward the O25 serogroup. Moreover, phages ϕEc1 and ϕEc3 decreased both biofilm formation and adherence, whereas ϕEc4 was able to decrease adherence but not biofilm formation. In conclusion, these novel phages showed the ability to decrease biofilm and bacterial adherence, making them promising candidates for effective adjuvant treatment against UTIs caused by MDR UPEC strains. Key points Phage with lytic activity against MDR UPEC strains were isolated and characterized under in vitro conditions. A novel method was proposed to evaluate phage activity against bacterial adherence in HEp-2 cell.. Phages represent a suitable strategy to control infections caused by MDR bacteria.

Background. Coagulopathic bleeding is a major cause of mortality after trauma, and platelet dysfunction contributes to this problem. The causes of platelet dysfunction are unknown, but a great deal can be learned from the plasma environment after injury, which may directly alter platelet function. Studying the changes in plasma using untargeted proteomics would provide unbiased insight into the presence of possible inhibitors of platelet function, changes to their major ligands, or other previously unknown pathways affecting platelet function. Methods. Citrated blood was collected from severely injured trauma patients at the time of their arrival to the Emergency Department. Platelet testing was performed immediately, and plasma was frozen for analysis. Samples were collected from 110 patients, and a subset of 24 patients was identified by a preserved (n=12) or severely impaired (n=12) platelet aggregation response to five different agonists (adenosine diphosphate, arachidonic acid, collagen, thrombin receptor-activating peptide, and ristocetin). Untargeted proteomics was performed by nanoflow liquid chromatography tandem mass spectrometry to determine the plasma protein profile associated with platelet dysfunction. Protein abundance levels for each patient were normalized to total protein concentration to control for hemodilution by crystalloid fluid infusion prior to blood draw. Results were compared by Wilcoxon rank-sum test, and a two-tailed p value less than 0.05 was considered significant. No adjustment was made for multiple comparisons, as the risk of a type II error was felt to outweigh that of a type I error in this exploratory analysis. Results. Patients with platelet dysfunction were more severely injured (median Injury Severity Score 29.5 vs. 13.5, p=0.002) but otherwise demographically similar to those with retained platelet function. Of 232 proteins identified, twelve were significantly different in the low- vs. high-platelet function groups: gelsolin (median peak intensity 9.70E+6 vs. 1.48 E+7, p=0.002), transketolase (2.86E+4 vs. 9.36E+3, p=0.003), protein S100-A8 (4.60E+4 vs. 2.64E+4, p=0.006) and -A9 (5.83E+4 vs. 4.07E+4, p=0.012), histone H4 (5.72E+4 vs. 8.47E+6, p=0.007), histidine-rich glycoprotein (HRG) (5.00E+6 vs. 8.30E+6, p=0.008), factor XIII B chain (1.09E+6 vs. 1.61E+6, p=0.020), apolipoprotein A-IV (2.30E+7 vs. 3.28E+7, p=0.024), alpha-enolase (1.02E+5 vs. 4.15E+4, p=0.024), heat shock protein 90-alpha (1.41E+4 vs. 4.08E+3, p=0.045), alpha-2-HS-glycoprotein (2.83E+7 vs. 3.68E+7, p=0.045), and neutrophil gelatinase-associated lipocalin (3.44E+4 vs. 1.36E+4, p=0.045). These results are summarized in the figure, which shows one group of proteins that decreased in abundance (on the left side of the volcano plot) and another that increased (on the right side) in the patients with low platelet function. The twelve proteins that changed the most fall into several categories related to platelet function. Low gelsolin and high histone levels are each associated with microvascular obstruction by release of intracellular material that accumulates in small vessels and activates platelets. Low HRG and high damage-associated molecular pattern (DAMP) protein levels are consistent with massive innate immune activation, which can impair platelet function in many ways. Conclusion. This study provides an unbiased description of the change in proteomic profile associated with platelet dysfunction after trauma and identifies twelve proteins with the most profound changes. The pathways involving these proteins are salient targets for immediate investigation to better understand platelet dysfunction after trauma and identify targets for intervention. Figure Legend. Volcano plot depicting fold-change and statistical significance of individual proteins in patients with low vs. high platelet function. Dotted horizontal line represents p = 0.05. Twelve proteins showed a statistically significant p value. Figure Disclosures No relevant conflicts of interest to declare.

Background Novel immune checkpoint-based immunotherapies may benefit specific groups of prostate cancer patients who are resistant to other treatments. Methods We analyzed by immunohistochemistry the expression of B7-H3, PD-L1/B7-H1, and androgen receptor (AR) in tissue samples from 120 prostate adenocarcinoma patients treated with radical prostatectomy in Spain, and from 206 prostate adenocarcinoma patients treated with radical prostatectomy in Norway. Results B7-H3 expression correlated positively with AR expression and was associated with biochemical recurrence in the Spanish cohort, but PD-L1 expression correlated with neither of them. Findings for B7-H3 were validated in the Norwegian cohort, where B7-H3 expression correlated positively with Gleason grade, surgical margins, seminal vesicle invasion, and CAPRA-S risk group, and was associated with clinical recurrence. High B7-H3 expression in the Norwegian cohort was also consistent with positive AR expression. Conclusion These results suggest distinct clinical relevance of the two immune checkpoint proteins PD-L1 and B7-H3 in prostate cancer. Our findings highlight B7-H3 as an actionable novel immune checkpoint protein in prostate cancer.

Summary Background & aims Consumption of rapid digesting sugars by children are under increased scrutiny because of their contribution to unhealthy weight gain. Previous studies in adults and children have suggested that altering the blend of carbohydrates (CHOs) consumed may cause shifts in substrate utilization. The purpose of this study was to examine the effects of consuming a slow digesting carbohydrate (SDC) and rapid digesting carbohydrate (RDC) on CHO and fat oxidation, glucose, and insulin responses at rest, during exercise, and post-exercise rest in pre-pubescent children. Methods A randomized, double-blind, crossover design was used. Nineteen pre-pubescent children (n = 10 boys, n = 9 girls, mean ± standard error, age = 9.84 ± 0.37-yrs) participated. Visits to the laboratory began with a 30-min measurement of resting metabolism followed by consumption of either an RDC or SDC drink. Postprandial resting metabolism was recorded for 60-min, immediately followed by 60-min of submaximal cycling exercise while metabolism was recorded, which was immediately followed by another 60-min recording of post-exercise metabolism. Total CHO and fat oxidation, endogenous and exogenous CHO oxidation, blood glucose, and insulin were assessed. Results Total CHO oxidation rate (g∙min−1) was greater after the RDC drink at 60 min (p = 0.032). Endogenous CHO oxidation rate (g∙min−1) was greater after the SDC drink at 15 min (p ≤ 0.010). Cumulative endogenous CHO oxidation (g) was greater after the SDC drink at 45 min (p = 0.009). Endogenous CHO oxidation accounted for a greater proportion of substrate oxidation after the first 60-min rest period (p = 0.028), while exogenous CHO oxidation accounted for a greater proportion of substrate oxidation for the RDC at all time points (p ≤ 0.019). Conclusions The present study provides novel data suggesting that an SDC promotes greater endogenous substrate utilization in pre-pubertal children, which may have beneficial health impacts on energy intake and carbohydrate regulation/metabolism during growth and development. Clinical trials registry number NCT03185884, clinicaltrials.gov

AIMS To conduct a systematic review compiling an update on the pathophysiology of burning mouth syndrome (BMS) by reviewing the theories and studies published in the last 5 years that consider BMS a neuropathic disease. METHODS A literature review was carried out in April 2020 on the PubMed database by using the following MeSH terms: "(burning mouth OR burning mouth syndrome OR burning mouth pain OR sore mouth OR burning tongue OR oral neuropathic pain OR glossodynia OR stomatopyrosis) AND (etiopathogenesis OR etiopathological factors OR etiology)." RESULTS The research carried out according to the methodology found 19 case-control studies (1 of which was in vivo) and 1 RCT. Of the 19 included studies, 8 showed an evidence score of 2-; 8 showed 2+; another 2 showed 2++; and 1 showed 1+. Quality studies on this topic are insufficient and heterogenous. CONCLUSION In the pathogenesis of BMS, both peripheral and central neuropathies appear to play a pivotal role. Nevertheless, the balance between them varies from case to case and tends to overlap. BMS does not seem to be a result of direct damage to the somatosensory nervous system, but a dysfunction in it and in the brain network.

OBJECTIVES: Smoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom.METHODS: An established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information.RESULTS: When limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose.CONCLUSION: Although found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators.

Introduction Intramedullary spinal cord gangliogliomas (ISCGGs) account for 35%-40% of all intramedullary tumors in children. These tumors have a different algorithm for treatment and prognosis than other medullary tumors, such as astrocytomas and spinal ependymomas . The objective of the study was to review the literature and examine an approach to diagnosing and treating this tumor based on a case report of ISCGG diagnosed at our center. Method An exhaustive review of cases of ISCGG published via the PubMed-NCBI platform between 1911 and 2018 was performed, and each patient's epidemiological characteristics, tumor location, symptoms, radiological diagnosis and treatment were appended. Results A total of 167 cases of ISCGG were found, including our own. In our sample, 52% of patients were female and the most commonly affected age group was 0-9 years of age (35% of patients). Motor deficit has been found to be the main symptom in a larger proportion of adults patients versus pediatric patients. On X-ray, this tumor shows greater hyperintensity and contrast uptake than astrocytomas and ependymomas, as well as a higher percentage of intratumoral cysts. The BRAFV600E mutation is less common in spinal as opposed to supratentorial gangliogliomas. Surgery with complete resection is the treatment of choice. Only 19% of the patients in the sample received radiotherapy, and only 9% received chemotherapy as their only line of treatment. Conclusions ISCGGs are common in the pediatric population and require strong suspicion for proper diagnosis and treatment, as the risk of recurrence of ISCGGs is three times greater than that of supratentorial gangliogliomas.

Research into assisted living environments –within the area of Ambient Assisted Living (ALL)—focuses on generating innovative technology, products, and services to provide medical treatment and rehabilitation to the elderly, with the purpose of increasing the time in which these people can live independently, whether they suffer from neurodegenerative diseases or disabilities. This key area is responsible for the development of activity recognition systems (ARS) which are a valuable tool to identify the types of activities carried out by the elderly, and to provide them with effective care that allows them to carry out daily activities normally. This article aims to review the literature to outline the evolution of the different data mining techniques applied to this health area, by showing the metrics used by researchers in this area of knowledge in recent experiments.

To date, there is no study addressing the time-varying confounding bias in the association of handgrip strength (HGS) with all-cause or cardiovascular mortality. Therefore, we conducted marginal structural models (MSM) to provide causal estimations on the associations of HGS with all-cause and cardiovascular mortality in a representative sample of adults aged 50 years or older. Data from 29 countries including 121,116 participants (276,994 observations; mean age 63.7 years; 56.3 % women) free from prior heart attack or stroke were retrieved from consecutive waves of the Survey of Health, Ageing and Retirement in Europe (SHARE). During a median of 7.7 years follow-up (interquartile range 3.8-11.8) and 1,009,862 person-years, 6407 participants (5.3 %) died due to all causes, and 2263 (1.9 %) died due to cardiovascular diseases. Using repeated measures of handheld dynamometry, we determined absolute and relative to body mass index HGS of each participant. We applied adjusted MSM to estimate hazard ratios (HRs) associated with changes over time in HGS addressing the time-varying confounding bias. An increase of 5 kg in HGS was associated with a reduced risk of all-cause [HR 0.86, 95 % confidence interval (CI), 0.86-0.90], overall cardiovascular (HR 0.86, 95 % CI 0.82-0.86), heart attack (HR 0.90, 95 % CI 0.86-0.95), and stroke (HR 0.86, 95 % CI 0.82-0.90) mortality. The associations of relative HGS were of stronger magnitude in all cases. Our findings provide critical evidence on the importance of increasing general muscle strength in older adults to reduce mortality risk, particularly concerning cardiovascular causes.