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OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.
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The synthesis of new compounds is an important pillar for the advancement of the field of chemistry and adjacent fields. In this regard, over the last decades huge efforts have been made to not only develop new molecular entities but also more efficient sustainable synthetic methodologies due to the increasing concerns over environmental sustainability. In this context, we have developed synthetic routes to novel corannulene flanked imidazolium bromide NHC precursors both in the solid state and solution phases. Our work presents a comprehensive comparative study of mechanochemical routes and conventional solution-based methods. Green metrics and energy consumption comparison were performed for both routes reveal ball-milling generation of these compounds to be an environmentally greener technique to produce such precursors compared to conventional solvent-based methods. In addition, we have demonstrated proof-of-concept of the herein reported corannulene flanked NHCs to be robust ligands to transition metals and their ligand substitution reactions.
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Love is a phenomenon that occurs across the world and affects many aspects of human life, including the choice of, and process of bonding with, a romantic partner. Thus, developing a reliable and valid measure of love experiences is crucial. One of the most popular tools to quantify love is Sternberg's 45-item Triangular Love Scale (TLS-45), which measures three love components: intimacy, passion, and commitment. However, our literature review reveals that most studies (64%) use a broad variety of shortened versions of the TLS-45. Here, aiming to achieve scientific consensus and improve the reliability, comparability, and generalizability of results across studies, we developed a short version of the scale-the TLS-15-comprised of 15 items with 5-point, rather than 9-point, response scales. In Study 1 (N = 7,332), we re-analyzed secondary data from a large-scale multinational study that validated the original TLS-45 to establish whether the scale could be truncated. In Study 2 (N = 307), we provided evidence for the three-factor structure of the TLS-15 and its reliability. Study 3 (N = 413) confirmed convergent validity and test-retest stability of the TLS-15. Study 4 (N = 60,311) presented a large-scale validation across 37 linguistic versions of the TLS-15 on a cross-cultural sample spanning every continent of the globe. The overall results provide support for the reliability, validity, and cross-cultural invariance of the TLS-15, which can be used as a measure of love components-either separately or jointly as a three-factor measure.
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Amor , Conducta Sexual , Humanos , Reproducibilidad de los Resultados , Parejas Sexuales , Lenguaje , Psicometría , Encuestas y CuestionariosRESUMEN
The current study investigates attitudes toward one form of sex for resources: the so-called sugar relationships, which often involve exchanges of resources for sex and/or companionship. The present study examined associations among attitudes toward sugar relationships and relevant variables (e.g., sex, sociosexuality, gender inequality, parasitic exposure) in 69,924 participants across 87 countries. Two self-report measures of Acceptance of Sugar Relationships (ASR) developed for younger companion providers (ASR-YWMS) and older resource providers (ASR-OMWS) were translated into 37 languages. We tested cross-sex and cross-linguistic construct equivalence, cross-cultural invariance in sex differences, and the importance of the hypothetical predictors of ASR. Both measures showed adequate psychometric properties in all languages (except the Persian version of ASR-YWMS). Results partially supported our hypotheses and were consistent with previous theoretical considerations and empirical evidence on human mating. For example, at the individual level, sociosexual orientation, traditional gender roles, and pathogen prevalence were significant predictors of both ASR-YWMS and ASR-OMWS. At the country level, gender inequality and parasite stress positively predicted the ASR-YWMS. However, being a woman negatively predicted the ASR-OMWS, but positively predicted the ASR-YWMS. At country-level, ingroup favoritism and parasite stress positively predicted the ASR-OMWS. Furthermore, significant cross-subregional differences were found in the openness to sugar relationships (both ASR-YWMS and ASR-OMWS scores) across subregions. Finally, significant differences were found between ASR-YWMS and ASR-OMWS when compared in each subregion. The ASR-YWMS was significantly higher than the ASR-OMWS in all subregions, except for Northern Africa and Western Asia.
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Conducta Sexual , Azúcares , Humanos , Masculino , Femenino , Relaciones Interpersonales , Caracteres Sexuales , ActitudRESUMEN
BackgroundPeople who use drugs (PWUD) are a key target population to reduce the burden of hepatitis C virus (HCV) infection.AimTo assess risk factors and temporal trends of active HCV infection in PWUD in Madrid, Spain.MethodsWe conducted a retrospective study between 2017 and 2023, including 2,264 PWUD visiting a mobile screening unit. Data about epidemiology, substance use and sexual risk behaviour were obtained through a 92-item questionnaire. HCV was detected by antibody test, followed by RNA test. The primary outcome variable was active HCV infection prevalence, calculated considering all individuals who underwent RNA testing and analysed by logistic regression adjusted by the main risk factors.ResultsOf all participants, 685 tested positive for anti-HCV antibodies, and 605 underwent RNA testing; 314 had active HCV infection, and 218 initiated treatment. People who inject drugs (PWID) were identified as the main risk group. The active HCV infection rate showed a significant downward trend between 2017 and 2023 in the entire study population (23.4% to 6.0%), among PWID (41.0% to 15.0%) and PWUD without injecting drug use (7.0% to 1.3%) (p < 0.001 for all). These downward trends were confirmed by adjusted logistic regression for the entire study population (adjusted odds ratio (aOR): 0.78), PWID (aOR: 0.78), and PWUD non-IDU (aOR: 0.78).ConclusionsOur study demonstrates a significant reduction in active HCV infection prevalence among PWUD, particularly in PWID, which suggests that efforts in the prevention and treatment of HCV in Madrid, Spain, have had an impact on the control of HCV infection.
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Hepacivirus , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , España/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Hepatitis C/epidemiología , Adulto , Prevalencia , Persona de Mediana Edad , Abuso de Sustancias por Vía Intravenosa/epidemiología , Factores de Riesgo , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Consumidores de Drogas/estadística & datos numéricos , Asunción de Riesgos , Anticuerpos contra la Hepatitis C/sangre , Trastornos Relacionados con Sustancias/epidemiología , Conducta Sexual/estadística & datos numéricos , Adulto Joven , Encuestas y CuestionariosRESUMEN
The development of new green methodologies and their broader adoption for promoting sustainable development in chemistry laboratories and industry play a significant role in society, due to the economic importance of chemistry and its widespread presence in everyday life. Therefore, a sustainable approach to chemistry contributes to the well-being of the worldwide population and complies with the United Nations Sustainable Development Goals (UN SDGs) and the European Green Deal. The review highlights how batch and continuous mechanochemical methods are an eco-friendly approach for organic synthesis, with a lower environmental footprint in most cases, compared to solution-based procedures. The assessment is objectively based on the use of green metrics (e.g., atom and real atom economy, E-factor, process mass intensity, material parameter recovery, Eco-scale, stoichiometric factor, etc.) and indicators (e.g. DOZN tool and life cycle assessment, LCA, studies) applied to organic transformations such as synthesis of the amide bond, carbamates, heterocycles, active pharmaceutical ingredients (APIs), porphyrins, porous organic polymers (POPs), metal- or acid-catalysed processes, multicomponent and condensation reactions, rearrangements, etc. The generalized absence of bulk solvents, the precise control over the stoichiometry (i.e., using agents in a stoichiometrically rather than in excess), and the more selective reactions enabling simplified work-up procedures are the distinctive factors, marking the superiority of mechanochemical processes over solution-based chemistry.
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Enhanced vascular permeability at the site of injury is a prominent feature in acute inflammatory pain models, commonly assessed through the Evans Blue test. However, this invasive test requires euthanasia, thereby precluding further investigations on the same animal. Due to these limitations, the integration of non-invasive tools such as IRT has been sought. Here, we aimed to evaluate the use of thermography in a common orofacial pain model that employs formalin as a chemical irritant to induce local orofacial inflammation. Male Hannover rats (290-300 g, N = 43) were used. In the first approach, radiometric images were taken before and after formalin administration, assessing temperature changes and extravasated Evans Blue. The second approach included capturing pre- and post-formalin test radiometric images, followed by cytokine measurements in excised vibrissae tissue. Rats were anesthetized for vibrissae tissue collection, allowing correlations between thermographic patterns, nocifensive behavior duration, and cytokine levels in this area. Our findings revealed a positive correlation between local temperature, measured via thermography, and vascular permeability in the contralateral (r2 = 0.3483) and ipsilateral (r2 = 0.4502) side, measured using spectrophotometry. The obtained data supports the notion that thermography-based temperature assessment can effectively evaluate vascular permeability in the orofacial region.
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Formaldehído , Termografía , Ratas , Masculino , Animales , Formaldehído/efectos adversos , Termografía/métodos , Permeabilidad Capilar , Azul de Evans/efectos adversos , Dolor Facial/inducido químicamente , CitocinasRESUMEN
Successful implantation requires coordinated migration and invasion of trophoblast cells into a receptive endometrium. Reduced forkhead box M1 (FOXM1) expression limits trophoblast migration and angiogenesis in choriocarcinoma cell lines, and in a rat model, placental FOXM1 protein expression was significantly upregulated in the early stages of pregnancy compared to term pregnancy. However, the precise role of FOXM1 in implantation events remains unknown. By analyzing mice blastocysts at embryonic day (E3.5), we have demonstrated that FOXM1 is expressed as early as the blastocyst stage, and it is expressed in the trophectoderm of the blastocyst. Since controlled oxygen tension is determinant for achieving normal implantation and placentation and a chronic hypoxic environment leads to shallow trophoblast invasion, we evaluated if FOXM1 expression changes in response to different oxygen tensions in the HTR-8/SVneo first trimester human trophoblast cell line and observed that FOXM1 expression was significantly higher when trophoblast cells were cultured at 3% O2, which coincides with oxygen concentrations in the uteroplacental interface at the time of implantation. Conversely, FOXM1 expression diminished in response to 1% O2 that resembles a hypoxic environment in utero. Migration and angiogenesis were assessed following FOXM1 knockdown and overexpression at 3% O2 and 1% O2, respectively, in HTR-8/SVneo cells. FOXM1 overexpression increased transmigration ability and tubule formation. Using a 3D trophoblast invasion model with trophospheres from HTR-8/SVneo cells cultured on a layer of MATRIGEL and of mesenchymal stem cells isolated from menstrual fluid, we observed that trophospheres obtained from 3D trophoblast invasion displayed higher FOXM1 expression compared with pre-invasion trophospheres. Moreover, we have also observed that FOXM1-overexpressing trophospheres increased trophoblast invasion compared with controls. HTR-8/SVneo-FOXM1-depleted cells led to a downregulation of PLK4, VEGF, and MMP2 mRNA expression. Our current findings suggest that FOXM1 participates in embryo implantation by contributing to trophoblast migration and early trophoblast invasion, by inducing transcription activation of genes involved in these processes. Maternal-fetal communication is crucial for trophoblast invasion, and maternal stromal cells may induce higher levels of FOXM1 in trophoblast cells.
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Proteína Forkhead Box M1 , Placenta , Trofoblastos , Animales , Femenino , Humanos , Ratones , Embarazo , Ratas , Movimiento Celular , Implantación del Embrión , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Oxígeno/metabolismo , Placenta/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Trofoblastos/metabolismoRESUMEN
BACKGROUND: Developmental Dysplasia of the Hip (DDH) is a condition affecting hip joint development in children, presenting multiple manifestations. Immobilization methods to ensure hip concentricity, such as the human position and modified Lange position, vary in effectiveness and risks, especially avascular necrosis. The purpose of this study was to identify whether closed reduction (CR), with two different immobilization techniques, is effective in avoiding complications such as residual hip dysplasia (RHD), re-dislocation, and Avascular Necrosis (AVN). METHODS: A total of 66 patients with DDH (84 hips) were treated with two different techniques of immobilization (groups A and B); the mean age at the time of reduction was 8 (6-13) months. The rates of RHD, Re-dislocation, and AVN were determined with a minimum follow-up of 48 months in both techniques. RESULTS: The Chi-square analysis conducted across the study groups unveiled that patients in Group B demonstrated a protective effect against AVN compared to those in Group A (OR: 0.248, 95% CI: 0.072-0.847, p = 0.026). However, no statistically significant differences were found between the groups concerning RHD (p = 0.563) and re-dislocation (p = 0.909). CONCLUSIONS: After the initial Human Position immobilization, the second cast with the modified Lange "second position" demonstrated a protective effect compared with maintaining the Human Position immobilization throughout the immobilization period, reducing the likelihood of AVN development in patients undergoing closed reduction for developmental dysplasia of the hip.
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In this case-control study, we evaluated the association between serum antibodies against hepatitis E virus (HEV) and central nervous system (CNS) neurodegenerative disorders (NDs) in older people with dementia. The presence of anti-HEV antibodies was related to a higher adjusted odds ratio (aOR) of having CNS NDs by neuropathological diagnosis (aOR, 2.13; P = .007) and clinical/neuropathological diagnosis (1.84; P = .02). Besides, serum anti-HEV antibodies were directly related to neuropathological injury (higher vascular pathology [aOR, 1.97; P = .006]) and higher probability of Alzheimer-type pathology (1.84; P = .02). In conclusion, the presence of anti-HEV antibodies was related to higher odds of CNS NDs and neuropathological injury in older people.
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Demencia , Virus de la Hepatitis E , Hepatitis E , Enfermedades Neurodegenerativas , Humanos , Anciano , Hepatitis E/complicaciones , Hepatitis E/epidemiología , Estudios Seroepidemiológicos , Estudios de Casos y Controles , Anticuerpos Antihepatitis , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/complicaciones , Demencia/epidemiología , Demencia/complicaciones , Inmunoglobulina MRESUMEN
BACKGROUND: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. METHODS: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. RESULTS: A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. CONCLUSIONS: Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.
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COVID-19 , Humanos , ARN Subgenómico , SARS-CoV-2 , Tiempo de Internación , Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéuticoRESUMEN
Artificial molecular machines have captured the full attention of the scientific community since Jean-Pierre Sauvage, Fraser Stoddart, and Ben Feringa were awarded the 2016 Nobel Prize in Chemistry. The past and current developments in molecular machinery (rotaxanes, rotors, and switches) primarily rely on organic-based compounds as molecular building blocks for their assembly and future development. In contrast, the main group chemical space has not been traditionally part of the molecular machine domain. The oxidation states and valency ranges within the p-block provide a tremendous wealth of structures with various chemical properties. Such chemical diversityâwhen implemented in molecular machinesâcould become a transformative force in the field. Within this context, we have rationally designed a series of NH-bridged acyclic dimeric cyclodiphosphazane species, [(µ-NH){PE(µ-NtBu)2PE(NHtBu)}2] (E = O and S), bis-PV2N2, displaying bimodal bifurcated R21(8) and trifurcated R31(8,8) hydrogen bonding motifs. The reported species reversibly switch their topological arrangement in the presence and absence of anions. Our results underscore these species as versatile building blocks for molecular machines and switches, as well as supramolecular chemistry and crystal engineering based on cyclophosphazane frameworks.
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OBJECTIVE: To evaluate frailty, falls and perceptions of ageing among clinically stable individuals with HIV, engaged with remote healthcare delivered via a novel smartphone application. METHODS: This was a multi-centre European cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the five-item FRAIL scale. Present criteria were summed and categorized as follows: 0, robust; 1-2, pre-frail; 3-5, frail. Falls history and EQ-5D-5L quality of life measure were completed. Participants were asked their felt age and personal satisfaction with ageing. RESULTS: A total of 1373 participated, with a mean age of 45 (± 9.8) years. Frailty was uncommon at 2%; 12.4% fell in the previous year, 58.8% of these recurrently. Mood symptoms and pain were prevalent, at 43.3% and 31.8%, respectively. Ageing satisfaction was high at 76.4%, with 74.6% feeling younger than their chronological age; the mean felt age was 39.3 years. In multivariable analysis, mood symptoms and pain were positively associated with frailty, falls and ageing dissatisfaction. An increase in pain severity and mood symptoms were respectively associated with 34% and 63% increased odds of pre-frailty/frailty. An increment in pain symptoms was associated with a 71% increase in odds of falling. Pain was associated with ageing poorly, as were mood symptoms, with odds of dissatisfaction increasing by 34% per increment in severity. CONCLUSIONS: Although uncommon, frailty, falls and ageing dissatisfaction were seen in a younger cohort with medically stable HIV infection using a remote care model, promoting screening as advocated by European guidelines. These were more common in those with pain or mood symptoms, which should be proactively managed in clinical care and explored further in future research.
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Fragilidad , Infecciones por VIH , Telemedicina , Humanos , Anciano , Persona de Mediana Edad , Adulto , Fragilidad/epidemiología , Infecciones por VIH/complicaciones , Anciano Frágil , Estudios Transversales , Calidad de Vida , EnvejecimientoRESUMEN
IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4+ ≥ 500 cells/mm3 , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.
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Infecciones por VIH , Humanos , Estudios Retrospectivos , Polimorfismo de Nucleótido Simple , Factores Reguladores del Interferón/genética , Genotipo , Predisposición Genética a la Enfermedad , beta Carioferinas/genéticaRESUMEN
OBJECTIVES: Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. METHODS: The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). RESULTS: 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. CONCLUSIONS: Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT05171270.
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BACKGROUND: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. METHODS: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. RESULTS: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). KaplanâMeier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. CONCLUSIONS: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.
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COVID-19 , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Estudios Prospectivos , Estudios Retrospectivos , COVID-19/diagnóstico , COVID-19/genética , Enfermedad Crítica , Biomarcadores , Unidades de Cuidados IntensivosRESUMEN
A series of four photoluminescent Al and In complexes were synthesised using an environmentally-benign mechanosynthesis strategy. Sterically crowded 3,5-di-tert-butyl functionalised salophen and salen ligands and their respective complexes have been synthesised in the solid-state and fully characterised. Subsequent photophysics and electrochemistry studies of the resulting complexes suggest that these new group 13 complexes can be viable alternatives to traditional photoluminescent complexes based on expensive and low abundant noble metals. The herein-reported strategy avoids the use of organic solvents and provides a process with low environmental impact and enhanced energy efficiency.
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Complejos de Coordinación , Complejos de Coordinación/química , Ligandos , ColorRESUMEN
Helicobacter pylori is a Gram-negative bacterium that causes chronic gastric inflammation, which can lead to gastric neoplasia. Therefore, early diagnosis of H. pylori infection is crucial for effective treatment and prevention of complications. The aim of this study was to compare the sensitivity and specificity of the STANDARD™ F H. pylori Ag FIA stool antigen test (SD Biosensor) with the LIAISON® Meridian H. pylori SA for the diagnosis of H. pylori infection. A total of 133 stool samples from patients with suspected H. pylori infection were compared using the STANDARD™ F H. pylori Ag FIA stool antigen test (SD Biosensor), based on lateral flow assay, with the LIAISON® Meridian H. pylori SA. Of the 45 positive samples with LIAISON, 44 were also positive while 1 was negative in the STANDARD™ antigen test. However, this discrepant sample showed a chemiluminescence index of 1.18, very close to the cut-off point of 1. On the other hand, of 88 negative samples obtained with LIAISON, 83 were negative and 5 were positive in the STANDARD™ antigen test. Moreover, STANDARD™ F H. pylori Ag FIA assay has shown a sensitivity of 97.8% (95% CI: 88.2-99.9), a specificity of 94.3% (95% CI: 87.2-98.1), a PPV of 83.9% (95% CI: 68.9-92.4) and a NPV of 99.3% ((95% CI: 95.3-99.9). In conclusion, the STANDARD™ F H. pylori Ag FIA (SD Biosensor) on the STANDARD™ F2400 analyser is a highly sensitive, specific and suitable assay for the detection of H. pylori in stool samples.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Sensibilidad y Especificidad , Infecciones por Helicobacter/microbiología , Heces/microbiología , Antígenos BacterianosRESUMEN
The bis(amidinato)-heavier tetrylenes E(bzamP)2 (E = Ge (2a) and Sn (2b); bzamP = N-isopropyl-N'-(diphenylphosphanylethyl)benzamidinate), which are equipped with one heavier tetrylene (germylene or stannylene) and two phosphane fragments (one on each amidinate moiety) as coordinable groups, have been synthesized from the benzamidinum salt [H2bzamP]Cl and GeCl2(dioxane) or SnCl2 in 2:1 mol ratio. A preliminary inspection of their coordination chemistry has shown that their amidinate group can also be involved in the bonding with the metal atoms as tridentate ENP and tetradentate PENP' coordination modes have been observed for the ECl(bzamP)2 ligand of [Ir{κ3E,N,P-ECl(bzamP)2}(cod)] (E = Ge (3a) and Sn (3b); cod = η4-1,5-cyclooctadiene) and the E(bzamP)2 ligand of [Ni{κ4E,N,P,P'-E(bzamP)2}] (E = Ge (4a) and Sn (4b)), which are products of reactions of 2a and 2b with [IrCl(cod)]2 (1:0.5 mol ratio) and [Ni(cod)2] (1:1 mol ratio), respectively. These products contain a 5-membered NCNEM ring that results from the insertion of the metal M atom into an E-N bond of 2a and 2b. Additionally, while iridium(I) complexes 3a and 3b are chloridotetryl derivatives (insertion of the tetrylene E atom into the Ir-Cl bond has also occurred) that have an uncoordinated phosphane group, nickel(0) complexes 4a and 4b contain a tetrylene fragment that, maintaining the lone pair, behaves as a σ-acceptor (Z-type) ligand.
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Oocyte activation via dual inhibition of protein synthesis and phosphorylation has improved in vitro embryo production in different mammalian species. In this study, we evaluated the effects of the combination of cycloheximide (CHX), dimethyl amino purine (DMAP), and anisomycin (ANY) on the activation of bovine oocytes, particularly on dynamics of MPF and MAPKs, embryonic developmental potential, and quality. The results showed that the cleavage and blastocyst rates, as well as levels of CCNB1, CDK1, p-CDK1Thr161, and p-CDK1Thr14-Tyr15, were similar among groups; ANY and ANY + CHX reduced the expression of ERK1/2 compared to DMAP-combinations (p < 0.05), whereas ANY + DMAP, CHX + DMAP, and ANY + CHX + DMAP reduced p-ERK1/2 compared to ANY and ANY + CHX treatments (p < 0.05). The quality of blastocysts in terms of cell counts, their allocation, and the numbers of TUNEL-positive cells did not differ among groups. However, transcript levels of POU5F1 were higher in embryos derived from ANY + CHX + DMAP treatment compared to other groups, while expression levels of CDX2 did not show differences. In addition, the BCL2A1/BAX ratio of the ANY + CHX + DMAP treatment was significantly low compared to the ANY treatment (p < 0.05) and did not differ significantly from the other treatments. In conclusion, oocyte activation by dual inhibition of protein synthesis and phosphorylation induces MPF inactivation without degradation of CCNB1, while MAPK inactivation occurs differentially between these inhibitors. Thus, although the combined use of these inhibitors does not affect early developmental competence in vitro, it positively impacts the expression of transcripts associated with embryonic quality.