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IntroductionISMiHealth is a clinical decision support system, integrated as a software tool in the electronic health record system of primary care, that aims to improve the screening performance on infectious diseases and female genital mutilation (FGM) in migrants. The aim of this study is to assess the health impact of the tool and to perform a process evaluation of its feasibility and acceptability when implemented in primary care in Catalonia (Spain).Methods and analysisThis study is a cluster randomised control trial where 35 primary care centres in Catalonia, Spain will be allocated into one of the two groups: intervention and control. The health professionals in the intervention centres will receive prompts, through the ISMiHealth software, with screening recommendations for infectious diseases and FGM targeting the migrant population based on an individualised risk assessment. Health professionals of the control centres will follow the current routine practice.A difference in differences analysis of the diagnostic rates for all aggregated infections and each individual condition between the intervention and control centres will be performed. Mixed-effects logistic regression models will be carried out to identify associations between the screening coverage and predictor factors. In addition, a process evaluation will be carried out using mixed methodology.Ethics and disseminationThe study protocol has been approved by the institutional review boards at Hospital Clínic (16 June 2022, HCB/2022/0363), Clinical Research Ethics Committee of the Primary Care Research Institute IDIAPJGol (22 June 2022, 22/113-P) and the Almería Research Ethics Committee (27 July 2022, EMC/apg). The study will follow the tenets of the Declaration of Helsinki and Good Clinical Practice. All researchers and associates signed a collaboration agreement in which they undertake to abide by good clinical practice standards.Findings will be disseminated in peer-reviewed journals and communications to congresses.Trial registration number NCT05868005.

In order to understand the role of cytosolic antioxidant enzymes in drought stress protection, transgenic tobacco (Nicotiana tabacum cv. Xanthi) plants overexpressing cytosolic Cu/Zn-superoxide dismutase (cytsod) (EC 1.15.1.1) or ascorbate peroxidase (cytapx) (EC 1.11.1.1) alone, or in combination, were produced and tested for tolerance against mild water stress. The results showed that the simultaneous overexpression of Cu/Znsod and apx or at least apx in the cytosol of transgenic tobacco plants alleviates, to some extent, the damage produced by water stress conditions. This was correlated with higher water use efficiency and better photosynthetic rates. In general, oxidative stress parameters, such as lipid peroxidation, electrolyte leakage, and H 2 O 2 levels, were higher in non-transformed plants than in transgenic lines, suggesting that, at the least, overexpression of cyt apx protects tobacco membranes from water stress. In these conditions, the activity of other antioxidant enzymes was induced in transgenic lines at the subcellular level. Moreover, an increase in the activity of some antioxidant enzymes was also observed in the chloroplast of transgenic plants overexpressing cytsod and/or cytapx. These results suggest the positive influence of cytosolic antioxidant metabolism on the chloroplast and underline the complexity of the regulation network of plant antioxidant defences during drought stress.

Background: There are multiple treatments and approaches available to manage pain. However, when these interventions fail to achieve adequate relief, pain management may involve the implantation of intrathecal infusion pumps. The use of ultrasound guidance may enhance nursing practice by improving procedural efficiency and patient comfort. This technique offers a more precise, safer, and less painful approach, potentially increasing patient satisfaction and reducing procedural complications. Aim: To evaluate patient pain levels during intrathecal infusion pump refills under ultrasound guidance compared to the traditional approach, also aiming to determine the time taken per technique and to assess related intra-procedural complications. Design: A prospective quasi-experimental pre-post study. Methods: The study population included individuals with intrathecal infusion pumps. Each participant underwent two refill visits: one using the traditional method and the subsequent refill using ultrasound guidance. The time required to complete the procedure, any complications, and pain related to the procedure were measured for both techniques. Time was measured using a stopwatch, and pain was assessed at the end of each procedure using a Visual Analogue Scale (VAS). Results: A total of 45 patients (25 men and 20 women), with a median age of 56.0 years were included. The estimated mean refill duration was 13.67 min for the traditional method versus 7.26 min for ultrasound-guided refills, representing a 53.2% reduction. The adjusted mean VAS was 2.76 (2.27–3.24) with ultrasound versus 5.91 (5.20–6.62) with the traditional method, yielding an adjusted mean difference of −3.16 (−4.02 to −2.30; p < 0.001). Reductions were consistent across subgroups defined by sex, refill duration, inter-procedural interval, intrathecal medication, and medical history. Complications occurred in 20.0% of traditional refills but in none of the ultrasound-guided procedures. Conclusions: Ultrasound guidance significantly reduces pain, complications, and procedure time, positioning it as the new standard of care for intrathecal pump refills. This mandates its immediate integration into nursing protocols and health management policies.

Background Cigarette smoking is an important risk factor for the development of cardiovascular disease, yet the pathways through which this may operate are poorly understood. Therefore, the mechanism underlying cigarette smoke (CS)-induced arterial endothelial dysfunction and the potential link with fractalkine/CX3CL1 upregulation were investigated. Methods and results Stimulation of human arterial umbilical endothelial cells (HUAECs) with pathophysiological concentrations of CS extract (1% CSE) increased CX3CL1 expression. Neutralisation of CX3CL1 activity under dynamic flow conditions significantly inhibited CSE-induced mononuclear cell adhesion to HUAECs (67%). The use of small interfering RNA (siRNA) revealed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (Nox5) but not Nox2 or Nox4 is the main NADPH isoform involved in CSE-induced CX3CL1 upregulation and mononuclear cell arrest. Knock down of HUAEC tumour necrosis factor α expression with siRNA or pharmacological inhibition of p38 mitogen-activated protein kinase and nuclear factor κB also abolished these responses. Interestingly, circulating monocytes and lymphocytes from patients with chronic obstructive pulmonary disease (COPD) (n=29) versus age-matched controls (n=23) showed CX3CR1overexpression. Furthermore, CX3CL1 neutralisation dramatically diminished their enhanced adhesiveness to CSE-stimulated HUAECs. Finally, when animals were exposed for 3 days to CS, a mild inflammatory response in the lung was observed which was accompanied by enhanced CX3CL1 expression in the cremasteric arterioles, an organ distant from the lung. CS exposure resulted in increased leukocyte–arteriolar endothelial cell adhesion which was significantly reduced (51%) in animals lacking CX3CL1 receptor (CX3CR1). Conclusions These results suggest that CS induces functional CX3CL1 expression in arterial endothelium and leukocytes from patients with COPD show increased CX3CL1-dependent adhesiveness. Therefore, targeting the CX3CL1/CX3CR1 axis might prevent COPD-associated cardiovascular disorders.

Nanoencapsulation with proteoliposomes from natural membranes has been proposed as a carrier for the highly efficient delivery of mineral nutrients into plant tissues. Since Boron deficiency occurred frequently in crops, and is an element with low movement in tissues, in this work, nanoencapsulated B vs free B was applied to in vitro sweet potato plants to investigate the regulation of B transporters (aquaporins and specific transporters). Additionally, an metabolomic analysis was performed, and mineral nutrient and pigment concentrations were determined. The results showed high increases in B concentration in leaves when B was applied as encapsulated, but also Fe and Mn concentration increased. Likewise, the metabolomics study showed that single carbohydrates of these plants could be related to the energy need for increasing the expression of most NIP aquaporins (NIP1;2, NIP1;3; NIP4;1, NIP4;2, NIP5;1, NIP6;1, and NIP7) and boron transporters (BOR2, BOR4 and BOR7;1). Therefore, the results were associated with the higher mobility of encapsulated B into leaves and the stimulation of transport into cells, since after applying encapsulated B, the aforementioned NIPs and BORs increased in expression.

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ . By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere. Synopsis A novel drug‐screening platform compatible with patient‐derived samples identifies effective therapies to prevent brain metastasis. METPlatform is a novel drug‐screening strategy to identify vulnerabilities of metastasis while colonizing organs ex vivo . METPlatform identified hits that were confirmed in vivo as effective against brain metastasis. METPlatform allows to dissect the molecular mechanisms downstream of target inhibition using omic approaches. METPlatform has a potential value as a patient \"avatar\". Graphical Abstract A novel drug‐screening platform compatible with patient‐derived samples identifies effective therapies to prevent brain metastasis.

One of the goals of computational chemists is to automate the de novo design of bioactive molecules. Despite significant advances in computational approaches to ligand design and binding energy evaluation, novel procedures for ligand design are required. Evolutionary computation provides a new approach to this design endeavor. We propose an evolutionary tool for de novo peptide design, based on the evaluation of energies for peptide binding to a user-defined protein surface patch. Special emphasis has been placed on the evaluation of the proposed peptides, leading to two different evaluation heuristics. The software developed was successfully tested on the design of ligands for the proteins prolyl oligopeptidase, p53, and DNA gyrase.

We present the MUSE Hubble Ultra Deep Survey, a mosaic of nine MUSE fields covering 90\\% of the entire HUDF region with a 10-hour deep exposure time, plus a deeper 31-hour exposure in a single 1.15 arcmin2 field. The improved observing strategy and advanced data reduction results in datacubes with sub-arcsecond spatial resolution (0.65 arcsec at 7000 A) and accurate astrometry (0.07 arcsec rms). We compare the broadband photometric properties of the datacubes to HST photometry, finding a good agreement in zeropoint up to mAB=28 but with an increasing scatter for faint objects. We have investigated the noise properties and developed an empirical way to account for the impact of the correlation introduced by the 3D drizzle interpolation. The achieved 3 sigma emission line detection limit for a point source is 1.5 and 3.1 10-19 erg.s-1.cm-2 for the single ultra-deep datacube and the mosaic, respectively. We extracted 6288 sources using an optimal extraction scheme that takes the published HST source locations as prior. In parallel, we performed a blind search of emission line galaxies using an original method based on advanced test statistics and filter matching. The blind search results in 1251 emission line galaxy candidates in the mosaic and 306 in the ultradeep datacube, including 72 sources without HST counterparts (mAB>31). In addition 88 sources missed in the HST catalog but with clear HST counterparts were identified. This data set is the deepest spectroscopic survey ever performed. In just over 100 hours of integration time, it provides nearly an order of magnitude more spectroscopic redshifts compared to the data that has been accumulated on the UDF over the past decade. The depth and high quality of these datacubes enables new and detailed studies of the physical properties of the galaxy population and their environments over a large redshift range.