IκB kinase-α coordinates BRD4 and JAK/STAT signaling to subvert DNA damage-based anticancer therapy.

Activation of the IκB kinase (IKK) complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification of downstream effectors other than NF-κB has remained elusive. Here, analysis of IKK-dependent substrates in CRC cells after UV treatment revealed that phosphorylation of BRD4 by IKK-α is required for its chromatin-binding at target genes upon DNA damage. Moreover, IKK-α induces the NF-κB-dependent transcription of the cytokine LIF, leading to STAT3 activation, association with BRD4 and recruitment to specific target genes. IKK-α abrogation results in defective BRD4 and STAT3 functions and consequently irreparable DNA damage and apoptotic cell death upon different stimuli. Simultaneous inhibition of BRAF-dependent IKK-α activity, BRD4, and the JAK/STAT pathway enhanced the therapeutic potential of 5-fluorouracil combined with irinotecan in CRC cells and is curative in a chemotherapy-resistant xenograft model. Finally, coordinated expression of LIF and IKK-α is a poor prognosis marker for CRC patients. Our data uncover a functional link between IKK-α, BRD4, and JAK/STAT signaling with clinical relevance.

The experiences of family members of persons with intellectual disabilities who used residential care homes during the COVID-19 pandemic.

BACKGROUND: The global COVID-19 pandemic has shown the vulnerability of some population groups, including persons with intellectual and developmental disabilities (IDD). AIM: The present paper will provide more clarity and understanding of the experiences of family members of persons with IDD housed in residential facilities in Catalonia within the period of maximum restrictions during the COVID-19 pandemic. METHODS AND PROCEDURES: Semi-structured interviews were conducted using an interpretive phenomenological qualitative approach. Study participants consisted of 14 relatives of IDD individuals who were institutionalized in residence facilities or homes. The guiding questions emerged from group discussions with relatives of those with IDD who did not participate in the subsequent interviews. Drawing from this group, the factors that were identified to have had the greatest impact on their lives were later used to guide the interviews. Data collection was carried out in face-to-face individual interviews that were recorded together with the observations of two researchers between February and October 2022. RESULTS: Our analysis identified 4 main themes that developed into additional factors: the decision to stay at home or in the residence, fear, illness, and protocol. Individuals with IDD lost their daily routines, suffered from social isolation, and did not understand the situation. CONCLUSION: The results of this study allow for a better understanding of the experiences of families of persons with IDD in residential centres during the lockdown by identifying their needs and how to better support them in the future. OUTCOMES AND RESULTS: Knowledge and understanding of these events should allow for better management of similar situations in the future.

This study contributes to a growing body of research that examines the experiences of IDD individuals and their families during the early months of the COVID-19 pandemic. A qualitative phenomenological interpretative approach was used following the recommendations of qualitative research practices in health care. Our findings reveal that relatives of persons with IDD who lived in residential care homes felt that the residents were not adequately cared for by the staff, who applied measures for containment and contagion prevention that were disproportionate, resulting in their needs not being considered; these recommended measures had been developed for elderly care homes. Individuals with IDD lost their daily routines, suffered from social isolation, and did not understand the situation. The present findings show that residential care homes for persons with IDD require specific action protocols in crisis situations that are adapted to the needs and characteristics of each centre,thus adopting a model of care based on human rights.

Levels of microplastics and their characteristics in molluscs from North-West Mediterranean Sea: Human intake.

Microplastics (MPs) are accessible for organisms with active filter feeding strategies, as are many marine molluscs, which live attached or semi-buried in sediments. In the present study, MPs (from 0.02 to 5 mm) concentration, morphology, and composition were determined in consumed mollusc species of the Catalan coast (NW Mediterranean Sea). Microplastic concentrations, morphologic characteristics and composition were studied according to species, catchment zones and depuration condition. Finally, human intake of MPs through molluscs' consumption was determined. >2300 individuals were analysed, being 1460 MPs extracted and their size, and polymeric composition registered. Big oysters and mussels showed the highest MPs concentration by individual, with levels of 22.8 ± 14.4 and 18.6 ± 23.0 MPs/individual, respectively. Mean annual MPs (≥20 µm) consumption for adult population was estimated in 8103 MPs/year, with a 95th percentile of 19,418 MPs/year. It suggests that the consumption of molluscs is an important route of MPs exposure for the Catalan population.

High-throughput analysis of amnesic shellfish poisoning toxins in shellfish by ultra-performance rapid resolution LC-MS/MS.

The application of ultra-performance rapid resolution LC on a 1.8 microm particle-size column coupled with tandem MS (RRLC-MS/MS) is described for the analysis of amnesic shellfish poisoning (ASP) toxins in shellfish. Complete resolution among domoic acid (DA) and the isomers was achieved in less than 3 min. The method was intralaboratory validated for direct analysis of crude extracts without further cleanup. It showed LODs ranging from 0.05 to 0.09 mg/kg and a working range that complied with the current regulatory level for DA of 20 mg/kg, and with the level of 4.5 mg/kg recently proposed by the European Food Safety Authority. Confirmatory capabilities were demonstrated according to the Commission Decision 2002/657/EC criteria. The results obtained by RRLC-MS/MS agreed with those provided by the reference LC-UV method, both intralaboratory for the analysis of blind samples (R2 = 0.9751) and interlaboratory through participation in the proficiency test for ASP toxins during 2009 (z-score = -0.962 and 0.177 for low- and high-contaminated samples, respectively). RRLC-MS/MS provided fast analysis and additional confirmatory capabilities for direct analysis of crude extracts while the performance and reliability of the results were maintained, even in very complex matrixes.

[Assessing the implementation of a nutritional screening protocol in patients admitted to the Medicine Department of a local hospital]. / Evaluación de la aplicación de un protocolo de cribado nutricional en pacientes ingresados en el Servicio de Medicina de un hospital comarcal.

INTRODUCTION: Background: the techniques for screening and nutritional intervention in hospitalized patients are a cost-effective measure. In clinical practice the problem lies in their administration. Objective: to evaluate the implementation of a nutritional screening tool in patients admitted to our Medicine Ward (M). Material and methods: a single-center, prospective, observational study in patients admitted to M. Exclusion criteria: end-stage cancer patients, inpatient stay less than 72 h, and hospital readmission of previously included patients. One out of every 2 hospital admissions was selected. We assessed the following: whether nurses performed the screening test, the Short Nutritional Assessment Questionnaire (SNAQ); the score obtained; consultations with dieticians (ICD); prescribed nutritional support; and coding of malnutrition in the discharge report. Dieticians repeated the SNAQ for one in every 3 patients. Results: during the study period 726 patients were admitted, 377 were selected, and 315 were included. The nursing staff administered the SNAQ to 93.6% of patients and malnutrition was present in 19%. Dieticians detected malnutrition in 37.8%. In 41.9% of patients with severe malnutrition an ICD was performed, whereas in 40% of them no nutritional intervention was implemented. The diagnosis of malnutrition was recorded in the discharge report of 42.1% of our cases. Conclusion: Compliance with screening test administration was good, but there is disagreement with the assessment made by dieticians. For most malnourished patients nutritional support fals to be prescribed, no ICDs are performed, and a malnutrition diagnosis is not included in the discharge report.

INTRODUCCIÓN: Antecedentes: las técnicas de cribado e intervención nutricional en pacientes hospitalizados son una medida coste-efectiva. En la práctica clínica, el problema radica en cómo aplicarlas. Objetivo: evaluar la aplicación de un protocolo de cribado nutricional en pacientes hospitalizados en la Planta de Medicina (M). Material y métodos: estudio unicéntrico, prospectivo y observacional realizado a pacientes que ingresan en M. Los criterios de exclusión fueron: pacientes oncológicos en fase terminal, ingresos inferiores a 72 h y reingresos de pacientes previamente incluidos. Se seleccionaron 1 de cada 2 ingresos. Se evaluaron: si Enfermería había realizado el test de cribado, el Short Nutritional Assessment Questionnaire (SNAQ); la puntuación obtenida; las interconsultas a dietistas (ICD); el soporte nutricional prescrito, y el diagnóstico de desnutrición en el informe de alta. Los dietistas volvieron a administrar el SNAQ a 1 de cada 3 pacientes incluidos. Resultados: durante el periodo de estudio ingresaron 726 pacientes, se seleccionaron 377 y se incluyeron 315. Enfermería administró el SNAQ al 93,6% de los pacientes; presentaban desnutrición el 19%. La determinación realizada por los dietistas detectó un 37,8% de desnutrición. En el 41,9% de los que presentaban desnutrición severa se realizaron ICD; al 40% de ellos no se les realizó ninguna intervención nutricional, y el diagnóstico de desnutrición constaba en el informe de alta del 42,1% de los pacientes. Conclusión: existe un buen cumplimiento en la realización del test de cribado, pero existe también discordancia con la valoración de los dietistas. En la mayoría de los pacientes con desnutrición no se realizan ICD, no se prescribe soporte nutricional y no se hace constar el diagnóstico en el informe de alta.

Determination of dissolved domoic acid in seawater with reversed-phase extraction disks and rapid resolution liquid chromatography tandem mass spectrometry with head-column trapping.

Domoic acid (DA) is the principal neurotoxin responsible for amnesic shellfish poisoning (ASP) and is produced, among other species, by marine diatoms of the genus Pseudo-nitzschia. In this work, a method for the determination of dissolved DA and its isomers present in seawater has been developed, based on a solid-phase extraction (SPE) disks followed by rapid resolution liquid chromatography coupled with tandem mass spectrometry. SPE provided sample desalting and 20-fold concentration of dissolved DA, while complete resolution between DA and its isomers was achieved in less than 3 min with rapid resolution chromatography thus providing high sample throughput. Additionally, a simple on-column chromatographic procedure allowed head-column trapping of DA providing 15-fold higher sensitivity. The conditions developed in this work have shown appropriate quality parameters in a within-laboratory validation. The detection limit was 0.02 ng mL(-1) for the whole method, while trueness ranged between 92.1% and 110.6% recovery and precision between 8.4% and 19.0% relative standard deviation. Expanded uncertainty measured was 1.92, 0.23 and 0.03 for 10.0, 1.0 and 0.1 ng mL(-1) DA concentrations, respectively, which demonstrated the accuracy of this method for confirmation and quantification of DA present at very low concentration levels in seawater.

Evaluation of quantitative importance of egg lipids and fatty acids during embryos and larvae development in marine pelagophil teleosts: with an emphasis on Dentex dentex.

Quantitative compositin of Dentex dentex eggs lipid classes (LCs) and fatty acid (FA)s were measured and correlated to embryo and larva viability parameters (egg buoyancy, floating rate (FR), hatching rate, HR and survival rate, SR, at 0-5 days post hatch, dph) through 43 formulated models (38 using FAs, as independent variable, [R(2) = 0.641-0.859] and 5 using LC [R(2) = 0.459-0.739]). The sphingomyelin, phosphatidylcholine and 20:2(n-6) were significantly correlated with FR; phosphatidylserine + phosphatidylinositol with SR at 1 dph; steryl ester + waxes/triacylglycerol with HR and SR at 0 dph; 14:0 with SR at 1-5 dph; 18:1(n-9), summation operator18:1, 20:5(n-3)/20:4(n-6), summation operatormonounsaturated FAs (MUFAs), 20:5(n-3), 22:6(n-3)/20:5(n-3) and 18:3(n-3) with SR at 2-5 dph; 20:5(n-3) + 20:4(n-6) with FR and SR at 2-5 dph. It was also found that a 14:0, 18:1(n-9), summation operatorMUFA, 18:2(n-6), 18:3(n-3), 20:5(n-3), 22:6(n-3)/20:5(n-3) and 20:5(n-3)/20:4(n-6) equal to 3.3, 16.5, 32.5, 9, 1.3, 8, 1.5 and 7, respectively, perhaps can provide a SR at 3 and 5 dph of >70%. The results indicated the importance of the egg LCs and FAs quantitative composition for common dentex embryonic and larval development and a potential use of these factors to predict egg quality in teleosts.

Quantitative composition of vitellogenin-derived yolk proteins and their effects on viability of embryos and larvae of common dentex (Dentex dentex), a marine pelagophil teleost.

To evaluate the importance of the quantitative composition of vitellogenin (Vtg)-derived egg yolk proteins during initial events of Dentex dentex life, viable eggs were obtained from captive broodstocks. Viability parameters (Vps; egg buoyancy (FR), hatching rate (HR), and larval survival rate (SR) at 0, 3, and 5 days posthatch (dph)) were determined for 70 egg batches. Vtg-derived yolk proteins were purified from the eggs using cation-exchange chromatography, separated and detected by SDS-PAGE, identified and characterized using mass spectrometry, quantified using image densitometry, and finally correlated to VPs. The 77.97, 57.22, 22.22, 17.69, and 16.95 kDa proteins were identified as proteolytic products resulted from both VtgA and B. All the Vtg-derived yolk proteins were significantly correlated to VPs with a maximum explanatory effect (R(2)) of 0.634. The concentration of the 57.22 kDa protein was significantly correlated with PR, the 77.97, 57.22, 22.22, 17.69, and 16.95 kDa proteins with HR and SR at 0 dph, the 22.22, 17.69, and 16.95 kDa proteins with SR at 3 and 5 dph. The results showed the importance of yolk protein content in the egg for embryogenesis and early larval development and indicated its potential use to predict egg quality in teleosts.