BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis.

Deficiencies in the BRCA1 tumor suppressor gene are the main cause of hereditary breast and ovarian cancer. BRCA1 is involved in the Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer with ubiquitin E3 activity. The relevance of the BRCA1/BARD1 ubiquitin E3 activity for tumor suppression and DNA repair remains controversial. Here, we observe that the BRCA1/BARD1 ubiquitin E3 activity is not required for Homologous Recombination or resistance to Olaparib. Using TULIP2 methodology, which enables the direct identification of E3-specific ubiquitination substrates, we identify substrates for BRCA1/BARD1. We find that PCNA is ubiquitinated by BRCA1/BARD1 in unperturbed conditions independently of RAD18. PCNA ubiquitination by BRCA1/BARD1 avoids the formation of ssDNA gaps during DNA replication and promotes continuous DNA synthesis. These results provide additional insight about the importance of BRCA1/BARD1 E3 activity in Homologous Recombination.

Smart Design of ZnFe and ZnFe@Fe Nanoparticles for MRI-Tracked Magnetic Hyperthermia Therapy: Challenging Classical Theories of Nanoparticles Growth and Nanomagnetism.

Iron Oxide Nanoparticles (IONPs) hold the potential to exert significant influence on fighting cancer through their theranostics capabilities as contrast agents (CAs) for magnetic resonance imaging (MRI) and as mediators for magnetic hyperthermia (MH). In addition, these capabilities can be improved by doping IONPs with other elements. In this work, the synthesis and characterization of single-core and alloy ZnFe novel magnetic nanoparticles (MNPs), with improved magnetic properties and more efficient magnetic-to-heat conversion, are reported. Remarkably, the results challenge classical nucleation and growth theories, which cannot fully predict the final size/shape of these nanoparticles and, consequently, their magnetic properties, implying the need for further studies to better understand the nanomagnetism phenomenon. On the other hand, leveraging the enhanced properties of these new NPs, successful tumor therapy by MH is achieved following their intravenous administration and tumor accumulation via the enhanced permeability and retention (EPR) effect. Notably, these results are obtained using a single low dose of MNPs and a single exposure to clinically suitable alternating magnetic fields (AMF). Therefore, as far as the authors are aware, for the first time, the successful application of intravenously administered MNPs for MRI-tracked MH tumor therapy in passively targeted tumor xenografts using clinically suitable conditions is demonstrated.

Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial.

BACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.

Light-to-Heat Conversion of Optically Trapped Hot Brownian Particles.

Anisotropic hybrid nanostructures stand out as promising therapeutic agents in photothermal conversion-based treatments. Accordingly, understanding local heat generation mediated by light-to-heat conversion of absorbing multicomponent nanoparticles at the single-particle level has forthwith become a subject of broad and current interest. Nonetheless, evaluating reliable temperature profiles around a single trapped nanoparticle is challenging from all of the experimental, computational, and fundamental viewpoints. Committed to filling this gap, the heat generation of an anisotropic hybrid nanostructure is explored by means of two different experimental approaches from which the local temperature is measured in a direct or indirect way, all in the context of hot Brownian motion theory. The results were compared with analytical results supported by the numerical computation of the wavelength-dependent absorption efficiencies in the discrete dipole approximation for scattering calculations, which has been extended to inhomogeneous nanostructures. Overall, we provide a consistent and comprehensive view of the heat generation in optical traps of highly absorbing particles from the viewpoint of the hot Brownian motion theory.

Optimization of iron oxide nanoparticles for MRI-guided magnetic hyperthermia tumor therapy: reassessing the role of shape in their magnetocaloric effect.

Superparamagnetic iron oxide nanoparticles have hogged the limelight in different fields of nanotechnology. Surprisingly, notwithstanding the prominent role played as agents in magnetic hyperthermia treatments, the effects of nanoparticle size and shape on the magnetic hyperthermia performance have not been entirely elucidated yet. Here, spherical or cubical magnetic nanoparticles synthesized by a thermal decomposition method with the same magnetic and hyperthermia properties are evaluated. Interestingly, spherical nanoparticles displayed significantly higher magnetic relaxivity than cubic nanoparticles; however, comparable differences were not observed in specific absorption rate (SAR), pointing out the need for additional research to better understand the connection between these two parameters. Additionally, the as-synthetized spherical nanoparticles showed negligible cytotoxicity and, therefore, were tested in vivo in tumor-bearing mice. Following intratumoral administration of these spherical nanoparticles and a single exposure to alternating magnetic fields (AMF) closely mimicking clinical conditions, a significant delay in tumor growth was observed. Although further in vivo experiments are warranted to optimize the magnetic hyperthermia conditions, our findings support the great potential of these nanoparticles as magnetic hyperthermia mediators for tumor therapy.

New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo.

Dimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells. Different experimental approximations were performed in endothelial cells, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration in endothelial cells, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in these cells. Dimethyl fumarate alters the energetic metabolism of endothelial cells in vitro and in vivo through an unknown mechanism, which could be the cause or the consequence of its pharmacological activity. This new discovery on the targets of this compound could open a new field of study regarding the mechanism of action of dimethyl fumarate.

Electrodeposited Zinc Coatings for Biomedical Application: Morphology, Corrosion and Biological Behaviour.

The improvement of biodegradable metals is currently an active and promising research area for their capabilities in implant manufacturing. However, controlling their degradation rate once their surface is in contact with the physiological media is a challenge. Surface treatments are in the way of addressing the improvement of this control. Zinc is a biocompatible metal present in the human body as well as a metal widely used in coatings to prevent corrosion, due to its well-known metal protective action. These two outstanding characteristics make zinc coating worthy of consideration to improve the degradation behaviour of implants. Electrodeposition is one of the most practical and common technologies to create protective zinc coatings on metals. This article aims to review the effect of the different parameters involved in the electrochemical process on the topography and corrosion characteristics of the zinc coating. However, certainly, it also provides an actual and comprehensive description of the state-of-the-art of the use of electrodeposited zinc for biomedical applications, focusing on their capacity to protect against bacterial colonization and to allow cell adhesion and proliferation.

Multi-stimuli-responsive chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles as theranostic platforms for combined tumor magnetic resonance imaging and chemotherapy.

Chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles were formulated by interfacial polymer disposition plus coacervation, and loaded with gemcitabine. That (core/shell)/shell nanostructure was confirmed by electron microscopy, elemental analysis, electrophoretic, and Fourier transform infrared characterizations. A short-term stability study proved the protection against particle aggregation provided by the chitosan shell. Superparamagnetic properties of the nanoparticles were characterized in vitro, while the definition of the longitudinal and transverse relaxivities was an initial indication of their capacity as T2 contrast agents. Safety of the particles was demonstrated in vitro on HFF-1 human fibroblasts, and ex vivo on SCID mice. The nanoparticles demonstrated in vitro pH- and heat-responsive gemcitabine release capabilities. In vivo magnetic resonance imaging studies and Prussian blue visualization of iron deposits in tissue samples defined the improvement in nanoparticle targeting into the tumor when using a magnetic field. This tri-stimuli (magnetite/poly(ε-caprolactone))/chitosan nanostructure could find theranostic applications (biomedical imaging & chemotherapy) against tumors.

Thermodynamic Characterization of Rhamnolipid, Triton X-165 and Ethanol as well as Their Mixture Behaviour at the Water-Air Interface.

In many industrial fields, in medicine or pharmacy, there are used multi-component mixtures of surfactants as well as more and more often mixtures containing biosurfactants. Thus, in our study the mixtures of rhamnolipid (RL), ethanol (ET) and Triton X-165 (TX165) were applied. For these mixtures the surface tension of aqueous solutions with constant concentration and composition of ET and RL as well as the variable concentration of TX165 was measured. Based on the obtained results and the literature data, thermodynamic analyses of the adsorption process of ET, RL, TX165, binary mixtures of ET + RL, ET + TX165 and RL + TX165 as well as the ternary mixtures of RL + ET + TX165 at the water-air interface were made. This analysis allows to propose a new equation for calculation of the total ethanol concentration at the water-air interface using the Guggenheim-Adam adsorption isotherm. The constants in the Langmuir and Szyszkowski equations for each component of the studied mixtures as well as the composition of the mixed monolayer at the water-air interface were also successfully analysed based on the contribution of particular surface active compounds to the water surface tension reduction as well as based on the Frumkin isotherm of adsorption.

Rare Recombinant GI.5[P4] Norovirus That Caused a Large Foodborne Outbreak of Gastroenteritis in a Hotel in Spain in 2021.

Noroviruses are among the most important causes of acute gastroenteritis (AGE). In summer 2021, a large outbreak of norovirus infections affecting 163 patients, including 15 norovirus-confirmed food handlers, occurred in a hotel in Murcia in southeast Spain. A rare GI.5[P4] norovirus strain was identified as the cause of the outbreak. The epidemiological investigation determined that norovirus transmission might have been initiated through an infected food handler. The food safety inspection found that some symptomatic food handlers continued working during illness. Molecular investigation with whole-genome and ORF1 sequencing provided enhanced genetic discrimination over ORF2 sequencing alone and enabled differentiation of the GI.5[P4] strains into separate subclusters, suggesting different chains of transmission. These recombinant viruses have been identified circulating globally over the last 5 years, warranting further global surveillance. IMPORTANCE Due to the large genetic diversity of noroviruses, it is important to enhance the discriminatory power of typing techniques to differentiate strains when investigating outbreaks and elucidating transmission chains. This study highlights the importance of (i) using whole-genome sequencing to ensure genetic differentiation of GI noroviruses to track chains of transmission during outbreak investigations and (ii) the adherence of symptomatic food handlers to work exclusion rules and strict hand hygiene practices. To our knowledge, this study provides the first full-length genome sequences of GI.5[P4] strains apart from the prototype strain.

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway.

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.

Multifaceted Analysis of Cerebrospinal Fluid and Serum from Progressive Multiple Sclerosis Patients: Potential Role of Vitamin C and Metal Ion Imbalance in the Divergence of Primary Progressive Multiple Sclerosis and Secondary Progressive Multiple Sclerosis.

The progressive forms of multiple sclerosis (MS) primary progressive MS (PPMS) and secondary progressive MS (SPMS) are clinically distinguished by the rate at which symptoms worsen. Little is however known about the pathological mechanisms underlying the differential rate of accumulation of pathological changes. In this study, 1H NMR spectroscopy was used to measure low-molecular-weight metabolites in paired cerebrospinal fluid (CSF) and serum of PPMS, SPMS, and control patients, as well as to determine lipoproteins and glycoproteins in serum samples. Additionally, neurodegenerative and inflammatory markers, neurofilament light (NFL) and chitinase-3-like protein 1 (CHI3L1), and the concentration of seven metal elements, Mg, Mn, Cu, Fe, Pb, Zn, and Ca, were also determined in both CSF and serum. The results indicate that the pathological changes associated with progressive MS are mainly localized in the central nervous system (CNS). More so, PPMS and SPMS patients with comparable disability status are pathologically similar in relation to neurodegeneration, neuroinflammation, and some metabolites that distinguish them from controls. However, the rapid progression of PPMS from the onset may be driven by a combination of neurotoxicity induced by heavy metals coupled with diminished CNS antioxidative capacity associated with differential intrathecal ascorbate retention and imbalance of Mg and Cu.

Bacterial Response to the Surface Aging of PLA Matrices Loaded with Active Compounds.

The use of active components in biomaterials improves the properties of existing ones and makes it possible to obtain new devices with antibacterial properties that prevent infections after implantation, thus guaranteeing the success of the implant. In this work, cetyltrimethylammonium bromide (CTAB) and magnesium particles were incorporated into polylactic acid (PLA) films to assess the extent to which progressive aging of the new surfaces resists bacterial colonization processes. For this purpose, the films' surface was characterized by contact angle measurements, ToF-SIMS and AFM, and adhesion, viability and biofilm growth of Staphylococcus epidermidis bacteria on these films were also evaluated. The results show that the inclusion of Mg and CTAB in PLA films changes their surface properties both before and after aging and also modifies bacterial adhesion on the polymer. Complete bactericidal activity is exhibited on non-degraded films and films with CTAB. This antibacterial behavior is maintained after degradation for three months in the case of films containing a higher amount of CTAB.

Enantioselective synthesis of 4-amino-3,4-dihydrocoumarins and their non-cyclic hydroxyester precursors: Biological evaluation for the treatment of glioblastoma multiforme.

The stereoselective addition of ethyl acetate enolate to the C═N bond of N-tert-butylsulfinylimines has been investigated in depth. A significant effect of the LHMDS amount and the N-sulfinylimine nature on the stereoselectivity of the process was observed. Conditions were found where sulfinylimines of differently substituted salicylaldehydes derivatives, ethyl acetate, and LHMDS afforded the corresponding addition products as a single diastereomer in good yields. The developed protocol was successfully applied to the first stereoselective synthesis of differently substituted 4-amino-3,4-dihydrocoumarin derivatives. Computational models confirmed the prominent role of the ortho aryl substituent in the stereoselectivity of the process. A significant and selective cytotoxic activity against Glioblastoma Multiforme (GBM) cancer line has been determined for the noncyclic hydroxy ester derivative.

Influence of Agaricus bisporus establishment and fungicidal treatments on casing soil metataxonomy during mushroom cultivation.

The cultivation of edible mushroom is an emerging sector with a potential yet to be discovered. Unlike plants, it is a less developed agriculture where many studies are lacking to optimize the cultivation. In this work we have employed high-throughput techniques by next generation sequencing to screen the microbial structure of casing soil employed in mushroom cultivation (Agaricus bisporus) while sequencing V3-V4 of the 16S rRNA gene for bacteria and the ITS2 region of rRNA for. In addition, the microbiota dynamics and evolution (bacterial and fungal communities) in peat-based casing along the process of incubation of A. bisporus have been studied, while comparing the effect of fungicide treatment (chlorothalonil and metrafenone). Statistically significant changes in populations of bacteria and fungi were observed. Microbial composition differed significantly based on incubation day, changing radically from the original communities in the raw material to a specific microbial composition driven by the A. bisporus mycelium growth. Chlorothalonil treatment seems to delay casing colonization by A. bisporus. Proteobacteria and Bacteroidota appeared as the most dominant bacterial phyla. We observed a great change in the structure of the bacteria populations between day 0 and the following days. Fungi populations changed more gradually, with A. bisporus displacing the rest of the species as the cultivation cycle progresses. A better understanding of the microbial communities in the casing will hopefully allow us to increase the biological efficiency of the crop.

Effect of sarpogrelate treatment on 5-HT modulation of vascular sympathetic innervation and platelet activity in diabetic rats.

This study aimed to investigate whether the 5-HT2 receptor blockade alters the 5-HT effect on vascular sympathetic neurotransmission and platelet activation in type 1 diabetes. 28-day diabetes was obtained by alloxan (150 mg/kg; s.c.) in male Wistar rats, administering sarpogrelate (5-HT2 blocker; 30 mg/kg/day; p.o.) for 14 days. Blood glucose and body weight were monitored for 28 days. After 4 weeks of diabetes induction, food and drink intake, urine, plasma-platelet 5-HT, and platelet activation were determined in normoglycemic, non-treated diabetic and sarpogrelate-treated diabetic rats. Another set of diabetic rats were pithed to run the vascular sympathetic stimulation or exogenous noradrenaline administration, examining the induced vasoconstrictor responses. Sarpogrelate treatment significantly reduced drink intake and urine, whereas BW gain, hyperglycemia, and food intake were not modified in diabetic rats. The platelet activation and plasma 5-HT concentration were decreased (increasing the stored 5-HT platelet) by 5-HT2 blockade in diabetic animals. The sympathetic-induced vasoconstrictions were higher in non-treated than in sarpogrelate-treated diabetic rats. 5-HT inhibited these vasopressor responses, reproduced exclusively by the 5-HT1/5/7 receptor agonist, 5-CT. The 5-CT-produced inhibition was partly reversed by 5-HT1D or 5-HT7 antagonists (LY310762 or SB-258719, respectively), and totally annulled by the mixture of LY310762+SB-258719. Noradrenaline-caused vasoconstrictions were also decreased by 5-CT. In conclusion, our results reveal that 14-day sarpogrelate treatment improves polydipsia and polyuria, reduces platelet hyperactivation, plasma 5-HT and the vascular sympathetic tone, and changes 5-HT receptors inhibiting noradrenergic drive in diabetic rats: pre and/or postjunctional 5-HT1D/7 are involved in the sympatho-inhibition.

Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats.

Comorbid diabetes and depression constitutes a major health problem, worsening associated cardiovascular diseases. Fluoxetine's (antidepressant) role on cardiac diabetic complications remains unknown. We determined whether fluoxetine modifies cardiac vagal input and its serotonergic modulation in male Wistar diabetic rats. Diabetes was induced by alloxan and maintained for 28 days. Fluoxetine was administered the last 14 days (10 mg/kg/day; p.o). Bradycardia was obtained by vagal stimulation (3, 6 and 9 Hz) or i.v. acetylcholine administrations (1, 5 and 10 µg/kg). Fluoxetine treatment diminished vagally-induced bradycardia. Administration of 5-HT originated a dual action on the bradycardia, augmenting it at low doses and diminishing it at high doses, reproduced by 5-CT (5-HT1/7 agonist). 5-CT did not alter the bradycardia induced by exogenous acetylcholine. Decrease of the vagally-induced bradycardia evoked by high doses of 5-HT and 5-CT was reproduced by L-694,247 (5-HT1D agonist) and blocked by prior administration of LY310762 (5-HT1D antagonist). Enhancement of the electrical-induced bradycardia by 5-CT (10 µg/kg) was abolished by pretreatment with SB269970 (5-HT7 receptor antagonist). Thus, oral fluoxetine treatment originates a decrease in cardiac cholinergic activity and changes 5-HT modulation of bradycardic responses in diabetes: prejunctional 5-HT7 receptors augment cholinergic-evoked bradycardic responses, whereas prejunctional 5-HT1D receptors inhibit vagally-induced bradycardia.

Validación por expertos del contenido del diagnóstico enfermero de NANDA-I Fatiga (00093) / Expert Validation of the Content for the NANDA-I Nursing Diagnosis of Fatigue

Introducción: La fatiga constituye un importante problema de salud que precisa de una adecuada valoración, diagnóstico y planificación de cuidados enfermeros centrados en quienes la sufren. Objetivo: Validar el contenido del diagnóstico enfermero NANDA-I Fatiga (00093) en la versión incluida en una base de datos clínica. Métodos: Estudio descriptivo y exploratorio de validación de contenido diagnóstico mediante expertos siguiendo la propuesta de Fehring. El ámbito de estudio fue España. La recogida de datos se realizó entre los meses de junio 2019-marzo 2020. Los expertos participantes disponían de experiencia y formación en el uso de lenguajes estandarizados enfermeros. Resultados: De las 13 Características Definitorias con las que cuenta el diagnóstico incluido en la base de datos, siete fueron validadas como mayores, cinco como menores y una no fue validada. Los 16 Factores Relacionados del diagnóstico fueron validados. El Índice de Validez de Contenido del diagnóstico fue de 0,81. Conclusiones: El diagnóstico obtuvo un Índice de Validez de Contenido elevado. Los componentes del diagnóstico NANDA-I Fatiga (00093) en la versión de la base de datos clínica guardan correspondencia con los presentes en el diagnóstico NANDA-I Fatiga (00093) en la Clasificación NANDA-I 2018-2020. Se considera que la investigación actual contribuye a incrementar la precisión diagnóstica al identificar Características Definitorias claves de la presencia del diagnóstico. Al tiempo valida Factores Relacionados influyentes en el diagnóstico no incorporados en los componentes del diagnóstico NANDA-I Fatiga (00093) en la edición de la Clasificación NANDA-I 2018-2020(AU)

Introduction: Fatigue is an important health concern that requiring appropriate assessment, diagnosis and nursing care planning focused on those who suffer from it. Objective: To validate the content of NANDA-I nursing diagnosis of fatigue (00093) in the version included in a clinical database. Methods: Descriptive and exploratory study of diagnostic content validation by experts following Fehring's proposal. The setting of the study was Spain. Data collection was carried out between June 2019 and March 2020. The participating experts had experience and training in the use of standardized nursing languages. Results: Of the thirteen characteristics that define the diagnosis included in the database, seven were validated as major, five as minor and one was not validated. All sixteen related factors of the diagnosis were validated. The content validity index of the diagnosis was 0.81. Conclusions: The diagnosis obtained a high content validity index. The components of the NANDA-I diagnosis of fatigue (00093) in the clinical database version correspond with those present in the NANDA-I diagnosis of fatigue (00093) in the NANDA-I Classification 2018-2020. The current research is considered to contribute with an increase in diagnostic accuracy by identifying key defining characteristics for the diagnosis. At the same time, it validates related factors that have an influence on the diagnosis but are not incorporated among the components of the NANDA-I diagnosis of fatigue (00093) in the 2018-2020 edition of the NANDA-I Classification(AU)

Oral fluoxetine treatment changes serotonergic sympatho-regulation in experimental type 1 diabetes.

AIMS: This study investigated whether fluoxetine treatment changes the 5-HT regulation on vascular sympathetic neurotransmission in type 1 diabetes. MAIN METHODS: Four-week diabetes was obtained by a single alloxan s.c. administration in male Wistar rats, administering fluoxetine for 14 days (10 mg/kg/day; p.o.). Systolic blood pressure, heart rate, glycaemia, body weight (BW) evolution, creatinine, and blood urea nitrogen (BUN) were monitored. Afterward, rats were pithed to perform the vascular sympathetic stimulation. 5-HT1A/1D/2A receptors expression was analysed by Western blot in thoracic aorta. Both i.v. norepinephrine and the electrical stimulation of the spinal sympathetic drive evoked vasoconstrictor responses. KEY FINDINGS: Fluoxetine treatment significantly reduced the BW gain, hyperglycaemia, creatinine, and BUN in diabetic rats. The electrical-produced vasopressor responses were greater in untreated than in fluoxetine-treated diabetic rats. 5-HT decreased the sympathetic-produced vasopressor responses. While 5-CT, 8-OH-DPAT and L-694,247 (5-HT1/7, 5-HT1A and 5-HT1D agonists, respectively) reproduced 5-HT-evoked inhibition, the 5-HT2 activation by α-methyl-5-HT augmented the vasoconstrictions. The 5-CT sympatho-inhibition was reversed by 5-HT1A plus 5-HT1D antagonists (WAY-100,635 and LY310762, respectively), whereas ritanserin (5-HT2A antagonist) blocked the α-methyl-5-HT potentiating effect. Norepinephrine-generated vasoconstrictions were increased or diminished by α-methyl-5-HT or 5-CT, respectively. 5-HT1A/1D/2A receptors were expressed at vascular level, being 5-HT1A expression increased by fluoxetine in diabetic rats. SIGNIFICANCE: Our findings suggest that fluoxetine improves metabolic and renal profiles, changes the vasopressor responses, and 5-HT receptors modulating sympathetic activity in diabetic rats: 5-HT1A/1D are involved in the sympatho-inhibition, while 5-HT2A is implicated in the sympatho-potentiation, being both effects pre and/or postjunctional in nature.

Quality of Life in Long-Term Renal Transplant Patients: A Controversial Subject.

BACKGROUND: Kidney transplant (KT) is the best technique for renal replacement treatment in terms of survival, costs, and quality of life. Several factors have been related to health-related quality of life (HRQOL) at different times after KT. The objectives of the study were to quantify the HRQOL in a prevalent cohort of KT patients and to describe the variables that influenced HRQOL. METHODS: In this cross-sectional study of a cohort of 64 KT patients, we measured HRQOL using the 36-item Short Form Health Survey. Variables measured included the following: physical functioning, role physical (RP), bodily pain (BP), general perception of health, vitality, social functioning (SF), role emotional (RE), and mental health. Demographic and analytical variables were collected. We describe the variables that influenced HRQOL. RESULTS: A large dispersion was observed in the RP, BP, SF, and RE categories. There were no differences in values between men and women who underwent KT. Diabetes, previous dialysis, deceased donor, age, kidney function, anemia, and malnutrition were associated with worse scores. CONCLUSION: This study suggests that HRQOL in KT patients is very heterogeneous and highly polarized. The factors that influence HRQOL are multiple and need to be addressed globally. Further studies are needed to understand the factors that influence HRQOL in the long term.