Global bounds on the Type-III Seesaw

We derive general bounds on the Type-III Seesaw parameters from a global fit to flavor and electroweak precision data. We explore and compare three Type-III Seesaw realizations: a general scenario, where an arbitrary number of heavy triplets is integrated out without any further assumption, and the more constrained cases in which only 3 or 2 (minimal scenario) additional heavy states are included. The latter assumption implies rather non-trivial correlations in the Yukawa flavor structure of the model so as to reproduce the neutrino masses and mixings as measured in neutrino oscillations experiments and thus qualitative differences can be found with the more general scenario. In particular, we find that, while the bounds on most elements of the dimension 6 operator coefficients are of order 10−4 for the general and 3-triplet cases, the 2-triplet scenario is more strongly constrained with bounds between 10−5 and 10−7 for the different flavours. We also discuss how these correlations affect the present CMS constraints on the Type-III Seesaw in the minimal 2-triplet scenario

Low Ciprofloxacin concentrations select Multidrug-Resistant Mutants overproducing efflux pumps in clinical isolates of Pseudomonas Aeruginosa

Low antibiotic concentrations present in natural environments are a severe and often neglected threat to public health. Even if they are present below their MICs, they may select for antibiotic-resistant pathogens. Notably, the minimal subinhibitory concentrations that select resistant bacteria, and define the respective sub-MIC selective windows, differ between antibiotics. The establishment of these selective concentrations is needed for risk-assessment studies regarding the presence of antibiotics in different habitats. Using short-term evolution experiments in a set of 12 Pseudomonas aeruginosa clinical isolates (including high-risk clones with ubiquitous distribution), we have determined that ciprofloxacin sub-MIC selective windows are strain specific and resistome dependent. Nonetheless, in all cases, clinically relevant multidrug-resistant (MDR) mutants emerged upon exposure to low ciprofloxacin concentrations, with these concentrations being below the levels reported in ciprofloxacin-polluted natural habitats where P. aeruginosa can be present. This feature expands the conditions and habitats where clinically relevant quinolone-resistant mutants can emerge. In addition, we established the lowest concentration threshold beyond which P. aeruginosa, regardless of the strain, becomes resistant to ciprofloxacin. Three days of exposure under this sub-MIC "risk concentration" led to the selection of MDR mutants that displayed resistance mechanisms usually ascribed to high selective pressures, i.e., the overproduction of the efflux pumps MexCD-OprJ and MexEF-OprN. From a One-Health viewpoint, these data stress the transcendent role of low drug concentrations, which can be encountered in natural ecosystems, in aggravating the antibiotic resistance problem, especially when it comes to pathogens of environmental origin. IMPORTANCE It has been established that antibiotic concentrations below MICs can select antibiotic-resistant pathogens, a feature of relevance for analyzing the role of nonclinical ecosystems in antibiotic resistance evolution. The range of concentrations where this selection occurs defines the sub-MIC selective window, whose width depends on the antibiotic. Herein, we have determined the ciprofloxacin sub-MIC selective windows of a set of Pseudomonas aeruginosa clinical isolates (including high-risk clones with worldwide distribution) and established the lowest concentration threshold, notably an amount reported to be present in natural ecosystems, beyond which this pathogen acquires resistance. Importantly, our results show that this ciprofloxacin sub-MIC selects for multidrug-resistant mutants overproducing clinically relevant efflux pumps. From a One-Health angle, this information supports that low antimicrobial concentrations, present in natural environments, may have a relevant role in worsening the antibiotic resistance crisis, particularly regarding pathogens with environmental niches, such as P. aeruginosa. It has been established that antibiotic concentrations below MICs can select antibiotic-resistant pathogens, a feature of relevance for analyzing the role of nonclinical ecosystems in antibiotic resistance evolution. The range of concentrations where this selection occurs defines the sub-MIC selective window, whose width depends on the antibiotic

Avances en la caracterización de las redes de regulación mediadas por proteínas FUR en Anabaena sp. PCC 7120: análisis de la corregulación por NtcA y estudio de la participación de factores sigma

Las cianobacterias son organismos fotosintéticos que desempeñan un papel importante como productores primarios y contribuyen notablemente al mantenimiento de los ciclos de carbono, oxígeno y nitrógeno de la biosfera. Algunas cianobacterias como Anabaena sp. PCC 7120 son capaces de fijar nitrógeno, un proceso muy complejo y altamente regulado por diversos reguladores transcripcionales. Entre ellos destaca NtcA, un regulador global esencial para el desarrollo de células especializadas en el proceso de fijación de nitrógeno, denominadas heterocistos. En la regulación de esta fijación de nitrógeno también parecen estar implicadas proteínas de la familia FUR, que está formada por tres parálogos (FurA, FurB y FurC). FurA y FurC regulan directamente genes implicados en el desarrollo de heterocistos, algunos de los cuales están también regulados por NtcA. Además de intervenir en el metabolismo del nitrógeno, las proteínas FUR están implicadas en otros procesos como el metabolismo del hierro y zinc, la fotosíntesis o la respuesta a estreses.Estudios anteriores definieron una red de regulación mediada por proteínas FUR y, en este trabajo, se quiso determinar si esta red podía estar corregulada por NtcA. Los resultados de este trabajo indican que varios reguladores transcripcionales y sistemas de dos componentes de esta red de regulación están corregulados por proteínas FUR y NtcA. Además, también se ha analizado la participación de los factores sigma en esta red de regulación, habiéndose encontrado que varios factores sigma forman parte de estas redes. Estos resultados sugieren que las redes de regulación mediadas por las proteínas FUR podrían estar implicadas en la respuesta de las cianobacterias a la deficiencia de nitrógeno y que, dada la estrecha relación de los factores sigma con la respuesta a estreses en cianobacterias, también podrían jugar un papel importante en la respuesta a diversos estreses.<br /

Actualización de la intervención optométrica en el queratocono

El queratocono es un tipo de ectasia corneal, bilateral y asimétrica, relativamente frecuente en la población que conlleva la protusión apical de la córnea y la reducción del espesor corneal entre otros cambios morfológicos corneales; que, en consecuencia, producen la disminución de la calidad visual. En la actualidad, no se conoce a ciencia cierta sobre la etiología del queratocono, pero se estudia para conseguir un diagnóstico precoz siendo este muy importante para frenar su progresión y alcanzar la mejor corrección óptica posible. El objetivo de este trabajo, es realizar una actualización en la intervención optométrica en el queratocono profundizando en los tratamientos ópticos y quirúrgicos.<br /

New Insights into the Medieval Hispano-Muslim Panel Painting: The Alfarje Found in a Balearic Casal (Spain)

Hispano-Muslim culture flourished during the Middle Ages in the Iberian Peninsula and Balearic Islands. During the restoration of a Balearic nobiliary building (casal), several panels with polychrome decoration on the back side were found. They were part of an old Muslim wooden ceiling (alfarje). A multi-technique strategy including optical microscopy, infrared and μRaman spectroscopies, field emission scanning electron microscopy-X-ray microanalysis (FESEM-EDX), focused ion beam (FIB-FESEM-EDX), atomic force microscopy nanoindentation (AFM-NI), and gas chromatography-mass spectrometry (GC-MS) has been applied in the analysis of these panel paintings and has provided morphological and compositional data that have led to the identification of the materials and artistic technique as well as the alteration mechanisms due to the natural aging and the adverse conditions of conservation. As a novelty, this study has confirmed the use of indigo as a blue pigment, an unusual material in Hispano-Muslim panel painting. Apart from the notable change in the visual appearance observed in the paintings, the study has also confirmed a change in the mechanical resistance in the paint layers. These changes have been induced by the combination of the chemical and microbiological alteration mechanisms identified

Dos álbumes ilustrados para trabajar la inteligencia emocional y la diversidad.

En el proyecto de innovación propuesto se profundiza, de una parte, en la importancia de la inteligencia emocional y la tolerancia hacia la diversidad presentes en la sociedad, y, de otra, en las ventajas y oportunidades del uso del álbum ilustrado como herramienta a lo largo de la etapa de la Educación Primaria. Ambos ejes se combinan en el diseño y planteamiento metodológico de dos álbumes, Pirata (Ver anexo I) y Háblalo (Ver anexo II), que se podrán poner en práctica en cualquier curso de la etapa, con su adecuada lectura y análisis, así como con la realización de una serie de actividades relacionadas, adaptadas a la edad de los/as escolares.The proposed innovation project explores, on the one hand, the importance of emotional intelligence and tolerance towards the diversity present in society, and, on the other hand, the benefits and opportunities of using the picture book as a tool throughout the Primary Education level. Both axes are combined in the design and methodological approach of two picture books, Pirata (See Annex I) and Háblalo (See Annex II), which can be introduced in all grades of the school stage, with their appropriate reading and analysis, as well as the implementation of a series of related activities, adapted to the age of the student

Integrative and Collaborative Approach in the Chronic Management of Obesity in Primary and Tertiary Care Setting: Vall Hebron-SAP Muntanya Healthcare Route

Integrative approach; Obesity; Primary careEnfoque integrador; Obesidad; Atención primariaEnfocament integrador; Obesitat; Atenció primàriaIntroduction: In the context of obesity pandemic, the health care providers involved in the primary care should have a significant role. Several guidelines for the management of obesity in primary care were proposed recently. In general lines, these guidelines include recommendation on the baseline assessment, therapy, and algorithm for referral to specialized obesity clinic and follow-up. Nevertheless, at present, there is no guideline or protocol that continuously and bidirectionally links the two settings: primary care and specialized obesity clinic. Methods: We present a model of continuous, bilateral, and integrative interaction between primary care units and reference tertiary care setting in the chronic management of obesity that is already implemented in a public health system. Results: The novelty of our algorithm is that incorporates the support and continuous communication with the specialized obesity clinic of the tertiary care setting from the beginning in the management of a patient with obesity, in a bidirectional manner. Conclusion: This kind of bidirectional and continuous collaboration will help engage health care providers in the management of obesity, optimize efforts, shorten the time until proper intervention, personalize the approach and, finally, save costs for the health system

Risk of cancer in patients with inflammatory bowel diseases and keys for patient management

Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist

Liver fibrosis in non-alcoholic fatty liver disease and progression to hepatocellular carcinoma in patients with inflammatory bowel disease: a systematic review

The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn’s Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn’s disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice