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Background: Infection is one of the challenging complications after open reduction and internal fixation for ankle fractures. Previously published case series conclude that Staphylococcus aureus is the most frequent causative microorganism. An unexpected increase in Enterobacter cloacae infections after this surgery was observed in a preliminary analysis of data at the promoting center of the study. In traumatology, its incidence has been reported in chronic osteomyelitis, prosthetic infections, septic osteoarthritis, open fractures in children and adults, and fractures other than the ankle. Because of this unexpected finding, we decided to perform this study to analyze the demographic and microbiological variables of acute osteosynthesis infection after ankle fracture and determine the distinctive features of the patients with E cloacae infection. Methods: We performed a retrospective multicenter study including 4 university hospitals. All patients diagnosed with acute osteosynthesis infection after ankle fracture fixation between January 2015 and December 2018 were included. We analyzed demographic data, type of fracture, surgical technique, and microorganisms responsible for the infection. We performed a descriptive statistical analysis of the variables. Univariate and multivariate regression analysis were performed to compare patients with E cloacae infection to patients with infection caused by other microorganisms. Results: A total of 65 patients were included. A predominance of polymicrobial infections (24.62%), followed by infections caused by S aureus (23.07%) and E cloacae (23.07%) was observed. When E cloacae isolated in polymicrobial infections were added, the incidence of E cloacae as a causative microorganism increased to 32.3%. Patients with E cloacae infection were older (64/53, P = .008) and had a higher requirement of negative-pressure therapy after surgical debridement (71%/40%, P = .017). Conclusion: A high incidence of E cloacae infections was observed. Patients with E cloacae infection were generally older and required a higher use of negative-pressure therapy after debridement. Level of Evidence: Level V, mechanism-based reasoning.

Esta investigación reconoce la paz como un escenario en el que el conflicto está presente y en el que las diferentes posiciones deben aprender a convivir. Para ello, se plantea la pregunta: ¿Cómo se han transformado las prácticas pedagógicas de docentes y profesores en los últimos 20 años para la reconstrucción del tejido social en territorios afectados por el conflicto armado en Colombia? Estas prácticas buscan mediar las relaciones entre los individuos y sus tensiones, enseñando resiliencia y la capacidad de mitigar los efectos negativos que las expresiones de violencia pueden tener en el desarrollo de los jóvenes que viven en este contexto.

[Background and objective] The benefits of exercise in atrial fibrillation (AF) are not clear yet. The aim was to assess the effects of exercise on functional capacity, quality of life, symptoms and adverse events in AF patients., [Methods] Pubmed, Web of Science, Science Direct and CENTRAL databases were searched to collect the literature concerning AF and exercise. Studies using an endurance and/or strength exercise of at least one-month duration were included. The meta-analysis was conducted using the random-effects method., [Results] 10 randomised controlled trials were selected. The analysis reported a significant improvement in the maximum exercise capacity (SMCR = 0.35; CI95% = 0.18, 0.51; p < .001) after exercise intervention. In patients with paroxysmal and persistent AF, exercise improved significantly VO2peak (SMCR = 0.387; CI95% = 0.214, 0.561; p < .001). Moreover, patients with permanent AF showed significant results in the 6-min walk test (SMCR = 0.74; CI95% = 0.31, 1.17; p < .001) and the resting heart rate (SMCR = −0.51; CI95% = −0.93, −0.10; p = .0015) thanks to exercise. Regarding quality of life, there was an improvement trend in the physical component score (SMCR = 0.13; CI95% = −0.05, 0.31; p = .17) and mental component score (SMCR = 0.09; CI95% = −0.09, 0.27; p = .35) in the exercise group. Nevertheless, pharmacological treatment tended to control the systolic blood pressure (SMCR = 0.13; CI95% = −0.03, 0.3; p = .11)., [Conclusion] Exercise has a beneficial role as an adjuvant treatment of AF., [Antecedentes y objetivo] Los beneficios del ejercicio físico en la fibrilación auricular (FA) todavía no están claros. El objetivo fue evaluar los efectos del ejercicio físico sobre la capacidad funcional, la calidad de vida, los síntomas y los episodios adversos en pacientes con FA., [Métodos] Se realizó una búsqueda en las bases de datos: Pubmed, Web of Science, Science Direct y CENTRAL para reunir la literatura relativa a FA y ejercicio. Los estudios incluidos utilizaron ejercicio aeróbico y/o fuerza de al menos un mes de duración. El metaanálisis fue elaborado mediante el método de efectos aleatorios., [Resultados] Se seleccionaron 10 ensayos controlados y aleatorizados. El análisis mostró mejoras significativas en la máxima capacidad de ejercicio (SMCR = 0,35; IC95% = 0,18, 0,51; p< 0,001) después del ejercicio. En pacientes con FA paroxística y persistente, el ejercicio mejoró significativamente el VO2pico (SMCR = 0,387; IC95% = 0,214, 0,561; p< 0,001). Además, pacientes con FA permanente mostraron resultados significativos en la prueba de marcha de 6 minutos (SMCR = 0,74; IC95% = 0,31, 1,17; p< 0,001) y en la frecuencia cardíaca en reposo (SMCR = -0,51; IC95% = -0,93, -0,10; p = 0,0015) gracias al ejercicio. A nivel de calidad de vida, hubo una tendencia de mejora en los resúmenes de los componentes físico (SMCR = 0,13; IC95% = -0,05, 0,31; p = 0,17) y mental (SMCR = 0,09; IC95% = -0,09, 0,27; p = 0,35) en el grupo ejercicio. Sin embargo, el tratamiento farmacológico tendió a regular mejor la presión arterial sistólica (SMCR = 0,13; IC95% = -0,03, 0,3; p = 0,11)., [Conclusión] El ejercicio físico tiene un papel beneficioso como tratamiento complementario de la FA.

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer

Pembrolizumab is licensed for the treatment of pre-treated and PD-L1 positive non-small cell lung cancer (NSCLC), but response is heterogeneous. In this context, the Lung Immune Prognostic Index (LIPI) has been proposed as tool to prognosticate outcome.To investigate the real-world efficacy and safety of pembrolizumab in pre-treated NSCLC patients and the clinical utility of LIPI for patients' selection.Patients with pre-treated NSCLC and PD-L1 ≥ 1% treated with pembrolizumab were included in this retrospective series. The LIPI was used to classify patients in 3 prognostics subgroups according to the pre-treatment dNLR (derived neutrophil to lymphocyte ratio) and LDH in blood. The prognostic impact of the LIPI on progression free survival (PFS) and overall survival (OS) was evaluated with Cox regression. The combined effect of LIPI and other relevant prognostic factors was explored with multivariate regression.In total, 113 consecutive patients were included. Median (mPFS) and mOS was 4.3 (2.6-6.7) and 13.5 (10.3-17.7) months, respectively. Good-, intermediate-, and poor-LIPI was found in 54 (47.8%), 45 (39.8%), and 8 (7.1%) patients, respectively. Median PFS was 5.1 (2.8-9.1), 3.0 (2.5-6.8), and 1.4 (0.5-18.7) months, and mOS was 17.2 (12.0-26.4), 11.8 (8.4-17.1), and 3.7 (0.5-not calculable) months for good-, intermediate-, and poor-LIPI group, respectively. Patients with intermediate-LIPI and poor-LIPI had worse PFS versus good-LIPI, and statistically significant worse OS (p = 0.030 and p = 0.013, respectively). In the multivariate analysis, intermediate- versus good-LIPI (p = 0.190) was not independently associated to PFS or OS. Patients with both good-LIPI and high (≥ 50%) PD-L1 had better OS than all other subgroups defined by LIPI and PD-L1. Immune-related adverse events (irAEs) occurred in 47 (41.6%) patients (12.4% grade ≥ 3). In a time-varying analysis, irAEs were statistically associated with longer OS (HR 0.51, 0.31-0.84; p = 0.008).In our series, the outcome of pembrolizumab in pre-treated NSCLC is consistent with the registration trial. Lung Immune Prognostic Index is a readily available tool able to prognosticate outcome, also in PD-L1-high patients. The positive association between irAEs and OS might aid decision making.

This study aimed to assess how often overridden drug allergy alerts (ODAAs) lead to allergic adverse drug events (All-ADEs) and to evaluate the frequency with which drug allergy alerts (DAAs) were overridden and the reasons, as well as appropriateness of these overrides.A retrospective observational study of DAA generated between 2014 and 2016 was conducted. The corresponding DAA records were reviewed to determine the frequency of alert overrides. A chart review was performed on a subset of 194 ODAA (the first of every 3 chronologically ordered ODAA) to identify All-ADEs and to evaluate the override reasons and the appropriateness of these overrides.A total of 2044 DAAs were overridden (override rate of 44.8%). Most were triggered by a nonexact match (93.81%), when ordering nervous system (21.1%) and cardiovascular system (19.6%) drugs and were generated by physicians (72.7%). The main override reason was that the patient was already taking the drug or had previously tolerated the drug. Only 9.28% of ODAAs were inappropriately overridden. Six All-ADEs (3.09%) were identified and were due to anti-infective (1), antineoplastic (1), and iodinated-contrast (4) drug administration. Most All-ADEs were cutaneous and were mild. None was life-threatening or fatal. The All-ADEs rate was higher among inappropriately ODAA (15.79%, P = 0.013).Alert overrides are not exempt from clinical consequences, although few are associated with All-ADEs. It is necessary to identify the drugs involved in those reactions and to update allergy lists to generate only specific and important DAA and to avoid the negative consequences of overrides.

Supplementary Figure S1. Crebbp deficiency results in accelerated germinal center derived B-cell lymphoma development in mice. Supplementary Figure S2. Ep300 deficiency results in accelerated germinal center derived B-cell lymphoma development in mice. Supplementary Figure S3. Western blots showing the knockdown efficiency of shRNAs against human CREBBP in human DLBCL MD901 cells and H3K27ac reduction in MD901 cells transduced with shRNAs against human CREBBP, and stacked bar plot showing the genome-wide distribution of CREBBP ChIPseq peaks in OCI-Ly7 cells. Supplementary Figure S4. GSEA enrichment plots showing correlation of genes with >25% loss of H3K27ac at enhancers in VavP-Bcl2/shCrebbp tumours with ranked expression change between B220+ lymphoma cells from VavP-Bcl2/shCrebbp tumours (n=3) and VavP-Bcl2/GFP tumours (n=3). NES, normalized enrichment score. Supplementary Figure S5. Venn diagram showing the overlap of H3K4me2+H3K4me3-H3K27ac+ (active enhancer) peaks between human tonsilar IgD+ Naïve B cells (NBs) and CD77+ germinal center B cells (GCBs). Supplementary Figure S6. Pathway analysis of down-regulated genes in top 500 differentially expressed genes between murine VavP-Bcl2/shCrebbp tumours and VavP-Bcl2/GFP tumours (left panel), or between CREBBP knockdown and scramble control human DLBLC MD901 cells (right panel). Supplementary Figure S7. Pathway analysis of genes with > 25% reduction of H3K27ac reads at promoters in murine VavP-Bcl2/shCrebbp tumors. Supplementary Figure S8. UCSC read-density tracks of normalized BCL6 (purple) and SMRT (orange) ChIP-seq reads in human tonsilar GCBs, H3K27ac ChIP-seq reads in human tonsilar NBCs (red) and GCBs (blue), and H3K27ac ChIP-seq in control scramble (Scr, green) and CREBBP KD (shCREBBP, turquoise) MD901 cells at the human CIITA and CD74 loci. BCL6 and SMRT peaks determined by MACS2 are indicated by grey bars under the read density track. Supplementary Figure S9. Stacked bar plots showing the frequencies of CREBBP somatic mutations in two cohorts of FL and one cohort of DLBCL primary patient samples. Supplementary Figure S10. The proportions of the Up (up-regulated) and Down (down-regulated) genes in the top 100, 500, and 1000 most differentially expressed genes of the respective cohorts profiled in Figure 3. Supplementary Figure S11. Representative flow cytometry analysis for FAS and GL7 of whole spleens from NS-DAD wild type (wt) or mutant (mut) animals. Supplementary Figure S12. Western blots showing the knockdown efficiency of shRNAs against human HDAC3 in DLBCL cell lines OCI-Ly7 and MD901 120 hr after induction of shRNA expression. The amount of HDAC3 was quantified by using ImageJ, and the ratio of shRNA knockdown samples and the control shLuc sample was indicated below the blots. Supplementary Figure S13. BCL6 and HDAC3 ChIP-qPCR at enhancers of CD74 or HLA-DOA (primer sequences please check Supplementary Table S12) in OCI-Ly1 cells transfected with either non-target siRNA (siNT) or BCL6 siRNA (siBCL6). Supplementary Figure S14. Quantification of HLA-DR measured by flow cytometry in shCREBBP or scramble transduced lymphoma cells MD901 and OCI-Ly18 in a second biological replicate experiment.

A list of CREBBP mutations in cohorts 1 and 2.

All the enriched pathways in various analyses.

A list of CREBBP mutations in cohort 3.

All pathways used in pathway enrichment analysis.

Patient info for cohorts 1 and 2.

A list of primer sequences used in Figure 5.

Cellular senescence is emerging as an important in vivo anticancer response elicited by multiple stresses, including currently used chemotherapeutic drugs. Nutlin-3a is a recently discovered small-molecule antagonist of the p53-destabilizing protein murine double minute-2 (MDM2) that induces cell cycle arrest and apoptosis in cancer cells with functional p53. Here, we report that nutlin-3a induces cellular senescence in murine primary fibroblasts, oncogenically transformed fibroblasts, and fibrosarcoma cell lines. No evidence of drug-induced apoptosis was observed in any case. Nutlin-induced senescence was strictly dependent on the presence of functional p53 as revealed by the fact that cells lacking p53 were completely insensitive to the drug, whereas cells lacking the tumor suppressor alternative reading frame product of the CDKN2A locus underwent irreversible cell cycle arrest. Interestingly, irreversibility was achieved in neoplastic cells faster than in their corresponding parental primary cells, suggesting that nutlin-3a and oncogenic signaling cooperate in activating p53. Our current results suggest that senescence could be a major cellular outcome of cancer therapy by antagonists of the p53-MDM2 interaction, such as nutlin-3a. [Cancer Res 2007;67(15):7350–7]

Supplementary Figure 1 from Induction of p53-Dependent Senescence by the MDM2 Antagonist Nutlin-3a in Mouse Cells of Fibroblast Origin

COVID-19 vaccine research in immune-deficient/disordered people (IDP) has primarily focused on cancer and organ transplantation populations. We followed 195 IDP with varied immune disorders and 35 healthy volunteers (HV) from April 2021-April 2022. Anti-spike IgG and angiotensin-converting enzyme 2 pseudo-neutralization were measured though six months post-dose 3. Anti-spike IgG was detected in 93% of IDP by six months post-dose 3. IgG dynamics in IDP and HV were similar, though median IgG levels for IDP were <33% of HV at all timepoints. IgG concentrations were lower against Omicron BA.1 than other variants at all timepoints. Pseudo-neutralization capacity was modestly correlated with anti-spike IgG concentration, but was especially low for Omicron BA.1. Post-vaccination adverse events were minimal. Results were largely unaffected by participants’ immunomodulatory medication and treatments. COVID-19 vaccines are safe, induce anti-spike IgG in most IDP, and should be more strongly recommended for people with immunodeficiencies.

Introduction Fournier's gangrene (FG) is a necrotising fasciitis affecting the perineum and urogenital tissue. The mortality rate is high although early detection and aggressive debridement can reduce mortality by up to 16%. The prevalence of sequelae is very high and a colostomy is often necessary to control the perineal wound. Material and Methods A retrospective study was carried out to recruit all patients operated on by the General Surgery and Urology Departments with a diagnosis of GF at the University Hospital over 22 years. Mortality, The Fournier Gangrene Severity Index (FGSI) and fecal diversion (either surgical (colostomy) or straight (Flexi-seal)) are collected. Results A total of 149 patients met the inclusion criteria. FG´s most frequent cause was a perianal abscess (107 patients - 72%). 18 patients (12%) died of a specific cause of FG. Age (p=0,014) and patients with an oncological history (p=0,038), both were the only mortality risk factors for mortality according to logistic regression. 50 patients required some form of fecal diversion in the postoperative period (32 colostomies and 18 flexi-seal). Neither the use of postoperative fecal diversion (surgical or Flexi-seal) nor the timing of its use had any effect on postoperative mortality. Conclusions One in eight patients died in the immediate postoperative period secondary to FG. Despite improved outcomes, 22% required a colostomy during admission. However, neither the performance of a colostomy nor the timing was associated with decreased FG-associated mortality. Non-invasive methods should be used first and surgical bowel diversion should be postponed as long as possible.

Across the globe, the healthcare sector is experiencing transformations (cultural, social, digital and economic). This is due to the age and varying patient needs that are driving a shift in the healthcare landscape. At the same time, chronic diseases, social determinants and resource limitations continue to add pressure. Healthcare has thus shifted from paternalistic mode of care to patient centered care (PCC). The growing multiple divergent medical cases denote a need to collaboratively understand clinical issues and effectively determine the best course of action. With PCC, a patient is recognized as a unique human being before forming a diagnosis. This implies that there is a need for multifaceted decision-making. In this study, we use a co-construction participatory modeling approach to understand the complexities in collaboratively managing knowledge for multi-morbid chronic patients on Advance Care Plan (ACP). To achieve this, focus group discussions (FGD) with 12 participants (five healthcare professionals, three health managers and three healthcare key decision makers) from Basque Public Health System (Osakidetza), in Spain were involved in identifying the key challenges and developing a systemic thinking model. As a result, three key challenges were identified i.e. 1) culture (citizens are not willing to talk about death, 2) healthcare professionals’ challenge to change attitude and perspectives, and 3) changing the current system towards holistic and a shared care model. From the developed Causal loop diagrams (CLDs), it is noted that perpetuation of fragmented and paternalistic care is likely to get worse without recognition of the ACP as a social need and a crucial part of the clinical practice part change.

CDSS contribute to reduce medication errors and/or adverse drug events as well as they can improve other clinical outcomes in the patient. This review aims to carry out a bibliographic review of the CDSS available up to the present time (May 2023) and collect the clinical impact of the different prescription support tools.

Immune checkpoint inhibitors (ICIs) and targeted therapies have revolutionised the diagnostic and treatment paradigm of advanced non-small cell lung cancer (NSCLC). However, treatment advances in squamous cell subtype have been much slower than those occurring in adenocarcinoma, mainly due to the lack of targetable oncogenic aberrations in squamous tumours. The unprecedented durable response and favourable toxicity profile observed with ICIs in advanced squamous NSCLC, represents a true therapeutic milestone in a population previously limited to cytotoxic chemotherapy (Cht). The inhibition of programmed cell death ligand 1 (PD-1/PD-L1) pathway has been extensively investigated in NSCLC and currently dominates the treatment landscape of advanced NSCLC. The first approval of ICIs came from several randomized trials conducted in platinum-treated advanced NSCLC patients (any histology) (1-4) where overall survival (OS) and toxicity profile favoured PD-1/PD-L1 inhibitors over docetaxel. Subsequently, KEYNOTE-024 (5) showed that, in advanced NSCLC patients (all histologies) with a PD-L1 tumour proportion score (TPS) ≥50%, first-line pembrolizumab achieved higher objective response rates (ORR) and longer progression-free survival (PFS) and OS when compared to standard platinum-based Cht. However, high PD-L1 expression only occurs in a third of NSCLC patients and, until recently, platinum-based Cht remained the only approved option for fit patients with a PD-L1 TPS

Some reproductive aspects of plant species may be conditioned by their flowering phenology. This might affect both the diversity and abundance of pollinators and the plants that constitute the community and, in turn, influence the degree of competition for pollinators. This study analyzed the plant floral display, floral rewards, and the pollination and breeding systems of two related species of Leucojum with different flowering phenology, the autumn-flowering L. autumnale L. and the spring-flowering L. trichophyllum Schousb. The main aim was to discover differences between both species that could be modeled by their differing flowering phenology. Our results showed that both species needed pollinators to reproduce sexually, with zero (L. trichophyllum) or almost zero values (c. 7.7%; L. autumnale) for fructification after self-pollination vs. over 90% after natural pollination (both species). Their flowers opened in the morning and closed at night, and neither produced nectar, only pollen as reward to pollinators. Plants of the L. autumnale population studied produced 1 to 4 inflorescences per plant vs. only 1 in L. trichophyllum, and the former presented a greater density of flowers per surface unit. Leucojum autumnale flowers were visited by Himenoptera in the morning and those of L. trichophyllum only received visits from two Coleoptera, these being most abundant at sunrise and sunset, whereas in the middle of the day they visited Cistaceae flowers. This latter occurrence represents facilitation rather competition in relation to visiting hours.

In this study, abnormal levels of myeloid activation, endothelial damage, and innate immune markers were associated with severe coronavirus disease 2019 (COVID-19), while higher levels of metabolic biomarkers (irisin, leptin) demonstrated a protective effect. These data support a model for COVID-19 immunopathogenesis linking robust inflammation and endothelial damage in metabolically predisposed individuals.

The aim of this paper is to present an experience of using various applications for classroom education at the Technological Institute of Campeche; in this way, as teachers respond to the training needs favorably, involving the use of ICT, linking systemically with knowledge, skills and attitudes of students, linking the pillars of education. Technologies of information and communication technologies (ICT) have become an important tool, especially in education. The use of the internet and different platforms to support teaching activities have been widely accepted in young people, facilitating the process of teaching and learning. It is therefore important that teachers know and use these platforms to implement strategies to promote the construction of learning. The results invite reflection of how ICT help teachers work

Diabetic nephropathy is a major complication in diabetic patients. Podocytes undergo loss and detachment from the basal membrane. Intra- and intercellular communication through exosomes are key processes for maintaining function, and the Rab3A/Rab27A system is an important counterpart. Previously, we observed significant changes in the Rab3A/Rab27A system in podocytes under glucose overload, demonstrating its important role in podocyte injury. We investigated the implication of silencing the Rab3A/Rab27A system in high glucose-treated podocytes and analysed the effect on differentiation, apoptosis, cytoskeletal organisation, vesicle distribution, and microRNA expression in cells and exosomes. For this, we subjected podocytes to high glucose and transfection through siRNAs, and we isolated extracellular vesicles and performed western blotting, transmission electron microscopy, RT-qPCR, immunofluorescence and flow cytometry assays. We found that silencing RAB3A and RAB27A generally leads to a decrease in podocyte differentiation and cytoskeleton organization and an increase in apoptosis. Moreover, CD63-positive vesicles experienced a pattern distribution change. Under high glucose, Rab3A/Rab27A silencing ameliorates some of these detrimental processes, suggesting a differential influence depending on the presence or absence of cellular stress. We also observed substantial expression changes in miRNAs that were relevant in diabetic nephropathy upon silencing and glucose treatment. Our findings highlight the Rab3A/Rab27A system as a key participant in podocyte injury and vesicular traffic regulation in diabetic nephropathy.

Three-Dimensionally Ordered Macroporous (3DOM) carbon surfaces were prepared from a template synthesis involving polymethyl methacrylate. These surfaces were mounted as electrodes and studied using cyclic voltammetry to understand their electrochemical properties for potential use as platforms in electrochemical sensors. The prepared 3DOM carbon electrodes have a large surface area that allows more charge-transfer reactions to take place. Potassium hexacyanoferrate and potassium nitrate served as the electroactive species and supporting electrolyte, respectively to study the 3DOM electrodes. Based on the Randles-Sevcik equation, the current produced by the potassium hexacyanoferrate electroactive species, is controlled by diffusion. The electrodes were subsequently chemically modified with 13 nm gold nanoparticles that produced a significant increase in the faradaic current.

The identity of Asperula asperrima Boiss., a species usually misidentified, is discussed, and when transferred to the genus Galium it requires a new name, here proposed as G. pierredmondii. This species is described, illustrated and compared with its closest relatives in the genus Galium, namely G. boissierianum and G. moralesianum. While G. boissierianum lives exclusively on peridotites and G. moralesianum on limestones and dolomites, the ecological behaviour of G. pierredmondii is much broader, inhabiting peridotites, schists, limestones and dolomites; furthermore, G. pierredmondii is partially sympatric with the former, from which it may derive the confusion involving both species. Synonymy is revised for the concerned names, and an updated identification key is reported for the Iberian taxa of G. sect. Galium.

The importance of many mutualistic interactions is poorly understood because information on their frequency and distribution at wide spatial scales is lacking. One such interaction is that between ants and plants bearing diaspores equipped with elaiosomes, which function as a reward for ants in exchange for dispersion. Our aim was to estimate the number of taxa having elaiosome-bearing diaspores in the Ibero-Balearic territory and its relationship to several factors. We estimated that at least 572 species and subspecies, almost one-third endemic, are present, which corresponds to ca. 5.1% of European angiosperms and 9% of Iberian ones. Because this number of elaiosome-bearing taxa is much higher than those given so far for the Northern Hemisphere, the Ibero-Balearic territory should be considered an important center of myrmecochory, with myrmecochorous species richness significantly positively correlated with ruggedness, latitude, and longitude. In contrast to other myrmecochorous territories (Australia and Cape Province), where numerous trees and shrubs develop on acid substrates, most myrmecochores in the Ibero-Balearic area are perennial herbs occupying basic substrates. Such perennial herbs are more frequent in the Eurosiberian floristic region, whereas annuals abound in the Mediterranean region. The enumerated taxa mainly inhabit forests, scrubs, and anthropized sites. Among them, 56.5% carry the elaiosome on seeds (especially strophiole and caruncle types). In 36.7%, the elaiosome is borne on indehiscent fruits, such as achenes in Asteraceae, where they are found either at the base of the style or the basal hilum, and at the base of nutlets (Boraginaceae and Lamiaceae).

PurposeThe authors propose the concept of “Autonomic Cycle for innovation processes,” which defines a set of tasks of data analysis, whose objective is to improve the innovation process in micro-, small and medium-sized enterprises (MSMEs).Design/methodology/approachThe authors design autonomic cycles where each data analysis task interacts with each other and has different roles: some of them must observe the innovation process, others must analyze and interpret what happens in it, and finally, others make decisions in order to improve the innovation process.FindingsIn this article, the authors identify three innovation sub-processes which can be applied to autonomic cycles, which allow interoperating the actors of innovation processes (data, people, things and services). These autonomic cycles define an innovation problem, specify innovation requirements, and finally, evaluate the results of the innovation process, respectively. Finally, the authors instance/apply the autonomic cycle of data analysis tasks to determine the innovation problem in the textile industry.Research limitations/implicationsIt is necessary to implement all autonomous cycles of data analysis tasks (ACODATs) in a real scenario to verify their functionalities. Also, it is important to determine the most important knowledge models required in the ACODAT for the definition of the innovation problem. Once determined this, it is necessary to define the relevant everything mining techniques required for their implementations, such as service and process mining tasks.Practical implicationsACODAT for the definition of the innovation problem is essential in a process innovation because it allows the organization to identify opportunities for improvement.Originality/valueThe main contributions of this work are: For an innovation process is specified its ACODATs in order to manage it. A multidimensional data model for the management of an innovation process is defined, which stores the required information of the organization and of the context. The ACODAT for the definition of the innovation problem is detailed and instanced in the textile industry. The Artificial Intelligence (AI) techniques required for the ACODAT for the innovation problem definition are specified, in order to obtain the knowledge models (prediction and diagnosis) for the management of the innovation process for MSMEs of the textile industry.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition characterized by the development of odontogenic keratocyst (OKC), basal cell carcinomas and palmar-plantar pits among other conditions. Reports about Latin American population are scarce.To analyze the clinical, radiographic, histopathologic and inherited features of odontogenic keratocyst and palmar pits in three Chilean families with nevoid basal cell carcinoma syndrome.After histopathologic diagnosis of OKC, notified consent was requested and evaluation of the affected patients and their families was done.Two families appeared to have only one affected adolescent, and both of them were considered de novo cases. In the third family, three affected members participated in this study, with an autosomal dominant presentation. All affected patients had OKC and palmar pits. Basal cell carcinomas were present only among adult patients. All examined patients were from Latin American ethnic groups.Patients with NBCCS had single or multiple OKCs that were located more frequently in the mandibular area. One family had autosomal dominant inheritance and the other two families were de novo cases. None of the three teenage patients had basal cell carcinomas.

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

Tato Laviera (1950-2013) fue un destacado poeta en la comunidad de inmigrantes denominados “neuyoricans”: puertorriqueños en Nueva York. En sus versos genera un spanglish muy personal, donde compara, negocia y elige los significados de cada lengua que le interesan; otras veces, suma aspectos culturales de ambos mundos. Incluso llega a producir significantes y significados que funden ambas culturas. Así el spanglish de Laviera se convierte en un material eficaz para la enseñanza de los dos idiomas: por un lado, ambas culturas se mantienen en constante comparación, con problemas sociales del siglo XX que siguen vigentes; por otro lado, es bien sabido en la didáctica de segundas lenguas, que los ritmos musicales que acompañan a estos poemas, además de resultar de máxima actualidad, constituyen una sinergia que favorece el aprendizaje.

The advent of PD-(L)1 and CTLA-4 immune check point inhibitors (CPIs) has dramatically changed the treatment landscape of advanced non-small-cell lung cancer (NSCLC). For up to a quarter of patients with advanced NSCLC, CPIs have the potential to induce durable responses with long-term survival outcomes. Since the approval of first-line pembrolizumab for patients whose tumors express a PD-L1 ≥ 50%, several pivotal first-line CPI-based phase 3 studies have been conducted investigating combination treatments combining CPIs with chemotherapy (ChT) or combining different CPIs with or without ChT. As a result, there has been an increase in front-line treatment options for advanced NSCLC, and treatment algorithms are changing very quickly. In fit patients with advanced NSCLC, combination treatments including CPI and ChT are considered the new standard of care with improved clinical outcomes. CPI combination treatments are well tolerated and quality of life also seems to be better when CPIs are implemented in the first-line setting. The aim of this review is to provide a summary of the recently published first-line phase 3 studies investigating CPIs as monotherapy or in combination with other CPIs or ChT in advanced NSCLC, and to suggest possible treatment algorithms.

Background Incorporating in the Intensive Care Unit (ICU) a clinical pharmacist who performs interventions on antimicrobials may be cost-effective. Objectives To evaluate the clinical and economic impact of clinical pharmacist interventions on antimicrobials in an ICU. To identify drug related problems and medication errors detected by the pharmacist. Methods A retrospective observational study was performed to analyze drug related problems, medication errors and clinical pharmacist interventions related to antimicrobials in adults admitted to an ICU in a 5-month period. The economic impact of pharmacist interventions was estimated considering difference in cost derived from antimicrobial treatment, adverse drug events and clinical pharmacist time. Results A total of 212 drug related problems were detected in 114 patients, 18 being medication errors. Clinical pharmacist developed one intervention for each problem identified. 204 interventions (96.2%) were considered important with improved patient care and 7 (3.3%) very important. No negative impact of any intervention was identified. Physicians accepted 97.6% of the interventions. A potential saving of 10,905 € was estimated as a result of pharmacist interventions and 4.8 € were avoided per euro invested in a clinical pharmacist. Conclusions A clinical pharmacist performing interventions on antimicrobials in the ICU has a positive impact on patient care and decreases costs.

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that has come from primary or metastatic cancer sites. Neoplasm-specific genetic and epigenetic abnormalities are increasingly being identified through liquid biopsy: a novel, minimally invasive technique used to isolate and analyze ctDNA in the peripheral circulation. Liquid biopsy and other emerging ctDNA technologies represent a paradigm shift in cancer diagnostics because they allow for the detection of minimal residual disease in patients with early-stage disease, improve risk stratification, capture tumor heterogeneity and genomic evolution, and enhance ctDNA-guided adjuvant and palliative cancer therapy. Moreover, ctDNA can be used to monitor the tumor response to neoadjuvant and postoperative therapy in patients with metastatic disease. Using clearance of ctDNA as an endpoint for escalation/de-escalation of adjuvant chemotherapy for patients considered to have high-risk disease has become an important area of research. The possibility of using ctDNA as a surrogate for treatment response–including for overall survival, progression-free survival, and disease-free survival–is an attractive concept; this surrogate will arguably reduce study duration and expedite the development of new therapies. In this review, we summarize the current evidence on the applications of ctDNA for the diagnosis and management of gastrointestinal tumors. Gastrointestinal cancers–including tumors of the esophagus, stomach, colon, liver, and pancreas–account for one-quarter of global cancer diagnoses and contribute to more than one-third of cancer-related deaths. Given the prevalence of gastrointestinal malignancies, ctDNA technology represents a powerful tool to reduce the global burden of disease.

Autoimmune diseases (ADs) are characterized by the activation of the immune system against self-antigens. More common in women than in men and with an early onset, their incidence is increasing worldwide, and this, combined with their chronic nature, is contributing to an enlarged medical and economic burden. Conventional immunosuppressive agents are designed to alleviate symptoms but do not constitute an effective therapy, highlighting a need to develop new alternatives. In this regard, mesenchymal stem cells (MSCs) have demonstrated powerful immunosuppressive and regenerative effects. MSC-derived extracellular vesicles (MSC-EVs) have shown some advantages, such as less immunogenicity, and are proposed as novel therapies for ADs. In this review, we summarize current perspectives on therapeutic options for ADs based on MSCs and MSC-EVs, focusing particularly on their mechanism of action exerted through their non-coding RNA (ncRNA) cargo. A complete state-of-the-art review was performed, centralized on some of the most severe ADs (rheumatoid arthritis, autoimmune type 1 diabetes mellitus, and systemic lupus erythematosus), giving evidence that a promising field is evolving to overcome the current knowledge and provide new therapeutic possibilities centered on MSC-EVs and their role as ncRNA delivery vehicles for AD gene therapy.

Due to population ageing and medical advances, people with advanced chronic diseases (ACD) live longer. Such patients are even more likely to face either temporary or permanent reduced functional reserve, which typically further increases their healthcare resource use and the burden of care on their caregiver(s). Accordingly, these patients and their caregiver(s) may benefit from integrated supportive care provided via digitally supported interventions. This approach may either maintain or improve their quality of life, increase their independence, and optimize the healthcare resource use from early stages. ADLIFE is an EU-funded project, aiming to improve the quality of life of older people with ACD by providing integrated personalized care via a digitally enabled toolbox. Indeed, the ADLIFE toolbox is a digital solution which provides patients, caregivers, and health professionals with digitally enabled, integrated, and personalized care, supporting clinical decisions, and encouraging independence and self-management. Here we present the protocol of the ADLIFE study, which is designed to provide robust scientific evidence on the assessment of the effectiveness, socio-economic, implementation, and technology acceptance aspects of the ADLIFE intervention compared to the current standard of care (SoC) when applied in real-life settings of seven different pilot sites across six countries. A quasi-experimental trial following a multicenter, non-randomized, non-concurrent, unblinded, and controlled design will be implemented. Patients in the intervention group will receive the ADLIFE intervention, while patients in the control group will receive SoC. The assessment of the ADLIFE intervention will be conducted using a mixed-methods approach.

Objectives To analyze the prevalence of May-Thurner syndrome (MTS) among patients with deep vein thrombosis (DVT) of left lower limb (LLL), and outcomes after long-term follow-up. Method Retrospective observational study that included patients older than 18 diagnosed with acute DVT and MTS. Results Among 760 patients diagnosed with DVT in the LLL, 8 patients were diagnosed with MTS (1.05%), with a mean age of 39 years. All patients received long-term anticoagulation, with a mean of 31.9 (±25.2) months. Invasive treatment with pharmaco-mechanical thrombectomy was performed in 5 patients (62.5%). During follow-up (mean of 32.4 months), 25% of patients suffered DVT recurrence. Only 1 case presented major bleeding, and no deaths were registered. Conclusions May-Thurner syndrome constitutes a permanent and underdiagnosed risk factor for the development of DVT of LLL. Our findings suggest that long-term anticoagulation therapy might be considered in selected cases.

The introduction of tyrosine kinase inhibitors (TKI) for the treatment of metastatic non-small cell lung cancer (NSCLC) harbouring sensitizing epidermal growth factor receptor (EGFR) gene mutations revolutionized the diagnostic and treatment algorithm of this subset of patients almost two decades ago. Since then, a number of trials have evaluated the role of TKI therapy in early-stage disease, with encouraging disease-free survival (DFS) results but lack of a survival advantage. ADAURA, a phase III trial evaluating 3 years of adjuvant osimertinib versus placebo in patients harbouring EGFR mutations with completely resected stage IB-IIIA NSCLC, recently reported a profound DFS benefit (hazard ratio 0.21), favourable quality of life and reduction in the risk of brain metastases. These results led to osimertinib's fast track approval by the US Food and Drug Administration, with this drug thus becoming the first EGFR-TKI approved for the treatment of early-stage disease. However, the key endpoint of overall survival remains immature and questions around indication (i.e. stage, need for adjuvant chemotherapy), optimal treatment duration, biomarkers of response and cost-effectiveness remain to be answered. In this article, we critically appraise the findings of ADAURA and discuss future challenges.

Objective: To identify which genes are associated with the clinical phenotype of amelogenesis Imperfecta (AI) and to elucidate which of these genes participate in the determination of isolated and syndromic forms.Methods: In this review, all data on mutations described in AI-related genes were obtained from HGMD® Professional. The data in relation to the mutations, inheritance, phenotype, type of AI and country were supplemented with information from the literature. The identity codes and frequency values were obtained from the dbSNP, ClinVar and OMIM databases. The percentage of specificity (PE) was determined for each gene.Results: HGMD® describes 27 genes involved in AI, which we propose to group into 5 categories: (1) genes whose mutations are associated only with isolated AI, (2) genes whose mutations cause only syndromic AI, (3) genes with both mutations that cause isolated AI and mutations responsible for other pathologies, (4) genes with mutations responsible for syndromic AI and mutations that cause other pathologies, and (5) genes with mutations that cause isolated AI and mutations that cause AI associated with syndromes and other pathologies. Using the PE calculation, the genes were ranked into 5 specificity groups. The genes of category 1 are specific for isolated AI, while the genes of categories 2 and 4 are non-specific. Interestingly, we observed that mutations in some genes were associated with different types of cancer.Conclusion: The ACP4, AMTN, MMP20, ODAPH, RELT, SLC24A4 and SP6 genes participate in causing isolated AI, and the CNNM4, DLX3 and FAM20A genes participate in causing syndromic forms of AI.