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Abstract The cultivated tomato, Solanum lycopersicum, is highly sensitive to cold stress (CS), resulting in significant losses during cultivation and postharvest fruit storage. Previously, we demonstrated the presence of substantial genetic variation in fruit chilling tolerance in a tomato recombinant inbred line (RIL) population derived from a cross between a chilling-sensitive tomato line and a chilling-tolerant accession of the wild species S. pimpinellifolium. Here, we investigated molecular and biochemical components associated with chilling tolerance in fruit and leaves, using contrasting groups of “chilling tolerant” and “chilling sensitive” RI lines. Transcriptomic analyses were conducted on fruit exposed to CS, and gene expressions and biochemical components were measured in fruit and leaves. The analyses revealed core responding genes specific to either the cold-tolerant or cold-sensitive RI lines, which were differentially regulated in similar fashion in both leaves and fruit within each group. These genes may be used as markers to determine tomato germplasm cold tolerance or sensitivity. This study demonstrated that tomato response to CS in different developmental stages, including seedling and postharvest fruit, might be mediated by common biological/genetic factors. Therefore, genetic selection for cold tolerance during early stages of plant development may lead to lines with greater postharvest fruit chilling tolerance.

Introduction: severe obesity results in high cardiovascular risk, increasing morbidity and mortality. New and improved methods are needed to detect cardiovascular diseases rapidly in severe obesity. microRNAs (miRNAs) has shown promise as diagnostic tools. This study aimed to identify plasma miRNAs useful as biomarkers of cardiovascular risk (CVR) in people with severe obesity. Methods: The study included 66 people with severe obesity classified in groups with atheroma (n = 32) and free of plaques (n = 34). Plasma samples were collected 1 month before bariatric surgery and at 6 and 12 months of follow-up. Participants were screened for the levels of 188 miRNAs, and 24 promising candidates were individually validated by quantitative polymerase chain reaction. Results: After validation, 5 of the 24 miRNAs showed significant differences over time in both groups: miR-375 increased after bariatric surgery, whereas miR-144-5p, miR-20a-3p, miR-145-5p and miR-21-3p exhibited decreased expression after bariatric surgery. The expression of 3 of the 24 miRNAs also differed between patients with and without atheroma: subjects with plaque had lower miR-126 but higher miR-21-3p and miR-133a-3p. Only miR-133a-3p exhibited exceptional discriminatory ability between subjects with and without plaque (area under the curve, 0.90; 95% confidence interval, 0.81–0.99). Conclusion: A specific signature of c-miRNA comprising miR-375, miR-144-5p, miR-20a-3p, miR-145-5p and miR-21-3p may facilitate CVR monitoring after bariatric surgery. Furthermore, miR-21-3p, miR-126-3p and miR-133a-3p show potential as specific biomarkers for subclinical atherosclerosis, with miR-133a-3p potentially able to diagnose subclinical atherosclerosis early in severe obesity.

Abstract Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

Abstract Background The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. Methods This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. Results At baseline, men had better executive function and global cognition than women (the effect size of gender differences was − 0.49, p = 0.015; and − 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen’s d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. Conclusions The MedDiet improved participants’ cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. Trial registration ISRCTN89898870.

Abstract Background Substantial weight loss in people living with type 2 diabetes (T2D) can reduce the need for glucose-lowering medications while concurrently lowering glycemia below the diagnostic threshold for the disease. Furthermore, weight-loss interventions have also been demonstrated to improve aspects of underlying T2D pathophysiology related to ectopic fat in the liver and pancreatic beta-cell function. As such, the purpose of this secondary analysis was to explore the extent to which a low-carbohydrate and energy-restricted (LCER) diet intervention improves markers of beta-cell stress/function, liver fat accumulation, and metabolic related liver function in people with type 2 diabetes. Methods We conducted secondary analyses of blood samples from a larger pragmatic community-based parallel-group randomized controlled trial involving a 12-week pharmacist implemented LCER diet (Pharm-TCR:

Abstract Background Paired sets and alternative set configurations (e.g., cluster sets) are frequently employed by strength and conditioning practitioners; however, their synergistic impact remains underexplored in research. This study aimed to elucidate whether the set configuration used in a lower-body exercise affects mechanical performance during paired sets of upper-body exercises. Methods Twenty-one resistance-trained individuals (14 men and 7 women) randomly completed three experimental sessions that involved four sets of five repetitions at 75%1RM during both the bench press and bench pull exercises. The three experimental sessions varied solely in the activity conducted during the inter-set rest periods of each upper-body exercise: (i) Traditional squat – six squat repetitions without intra-set rest at 65%1RM; (ii) Rest redistribution squat – two clusters of three repetitions of the squat exercise at 65%1RM with 30 s of intra-set rest; and (iii) Passive rest – no exercise. Results The rest redistribution set configuration allowed the sets of the squat exercise to be performed at a faster velocity than the traditional set configuration (p = 0.037). However, none of the mechanical variables differed between the exercise protocols neither in the bench press (p ranged from 0.279 to 0.875) nor in the bench pull (p ranged from 0.166 to 0.478). Conclusions Although rest redistribution is an effective strategy to alleviate fatigue during the sets in which it is implemented, it does not allow subjects to perform better in subsequent sets of the training session.

Las lesiones precancerosas del cuello uterino se refieren a cambios anormales que ocurren en las células del cuello uterino y que tienen el potencial de desarrollarse en cáncer si no se tratan a tiempo. Estas lesiones se clasifican en diferentes grados de acuerdo con la severidad y el tipo de células afectadas. Es importante entender esta definición para poder identificar y diagnosticar correctamente estas lesiones, lo que permite tomar medidas preventivas y terapéuticas adecuadas. Los factores de riesgo que se asocian a lesiones precancerosas según los estudios revisados destacan la importancia para prevenir el desarrollo de dichas lesiones. Algunos de los hallazgos clave incluyen procedencia rural, infección por el virus del papiloma humano (VPH), comportamiento sexual, estado del sistema inmunológico, tabaquismo, uso de anticonceptivos hormonales, nutrición, estilo de vida, historia reproductiva, exposición a sustancias químicas, así como factores genéticos y hereditarios. Comprender y abordar estos factores de riesgo nos permite implementar medidas efectivas de prevención y control de las lesiones precancerosas del cuello uterino. El estudio de los factores de riesgo asociados a las lesiones precancerosas del cuello uterino es fundamental para comprender la epidemiología de esta enfermedad y diseñar estrategias de prevención eficientes. Este conocimiento es crucial para informar a la población, promover la adopción de medidas preventivas y facilitar la detección temprana de la enfermedad, salvando así vidas y reduciendo la carga que supone el cáncer cervical en la sociedad.

Presentamos el caso de un paciente masculino ecuatoriano de 50 años, comerciante y residente de Ecuador, con un cuadro clínico de 2 meses de evolución caracterizado por síntomas respiratorios y hallazgos radiológicos sugestivos de tuberculosis pulmonar activa. El paciente presentó pérdida de peso significativa, tos persistente con expectoración blanquecina, fiebre vespertina, dolor torácico bilateral y disnea de medianos esfuerzos. En el examen físico, se observaron estertores crepitantes en la base pulmonar derecha y pérdida de panículo adiposo. La radiografía reveló un aumento de la densidad pulmonar con infiltrados algodonosos y pequeñas cavitaciones en ambos pulmones. Los resultados de laboratorio mostraron leucocitosis y neutrofilia importantes, elevación del PCR cuantitativo y Xpert MTB positivo en esputo, confirmando el diagnóstico. El reconocimiento temprano de los síntomas y hallazgos radiológicos característicos es esencial para iniciar el tratamiento adecuado.

La respuesta isotópica de Wolf (WIR) se refiere a la aparición de una nueva enfermedad de la piel en el sitio exacto de una enfermedad de la piel no relacionada que se había curado previamente. Se han descrito varias lesiones cutáneas después del herpes zóster, la definición de enfermedades cutáneas curadas que desencadenan una respuesta isotópica incluye cicatrices, cambios de pigmentación, cambios de color, la presencia de anhidrosis localizada como daño estructural u otros cambios mínimos causados por la primera enfermedad. Muchas lesiones cutáneas en el sitio de la HPZ curada se han descrito como WIR; por lo tanto, la HPZ es la enfermedad primaria más común para inducir WIR, y varios autores han sugerido un nuevo término, “respuesta isotópica postherpética de Wolf”.

La pandemia de la COVID-19 parecía haber dejado claro no sólo para los organismos gubernamentales, sino para la sociedad en su conjunto, la importancia de la ciencia. Nuestra revista publicó varias editoriales explicando y fundamentando la necesidad de la autonomía sanitaria cuyo requisito principal es la existencia de un sistema científico sólido y establecido. Un ejemplo claro fue la disponibilidad de vacunas para COVID-19, las cuales llegaron en tiempos disímiles por país y con retraso con respecto a los países que las desarrollaron; por supuesto, esas vacunas son producto de la ciencia de países que invierten significativamente en el sector. No hubo ningún país en Latinoamérica que pudiera desarrollar una vacuna con mayor antelación, y los países que se beneficiaron primero fueron los países con mayor desarrollo científico. Sin embargo, no fueron solo las vacunas pues también hubo dificultades importantes con reactivos de diagnóstico, respiradores y medicamentos. Sin ninguna ambigüedad, esto demuestra nuestra incapacidad para resolver problemas críticos para la supervivencia de los habitantes de nuestros países.

Abstract X-ray sources have a strong social impact, being implemented for biomedical research, material and environmental sciences. Nowadays, compact and accessible sources are made using lasers. We report evidence of nontrivial spectral-angular correlations in a laser-driven betatron X-ray source. Furthermore, by angularly-resolved spectral measurements, we detect the signature of spatial phase modulations by the electron trajectories. This allows the lateral coherence function to be retrieved, leading to the evaluation of the coherence area of the source, determining its brightness. Finally, the proposed methodology allows the unprecedented reconstruction of the size of the X-ray source and the electron beam emittance in the two main emission planes in a single shot. This information will be of fundamental interest for user applications of new radiation sources.

In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of the TGF-β nodal in the ventral ectoderm. nodal expression is first induced ubiquitously in the 32-cell embryo and becomes progressively restricted to the presumptive ventral ectoderm by the early blastula stage. This early spatial restriction of nodal expression is independent of Lefty, and instead relies on the activity of Panda, a maternally expressed TGF-β ligand related to Lefty and Inhibins, which is required maternally for D/V axis specification. However, the mechanism by which Panda restricts the early nodal expression has remained enigmatic and it is not known if Panda works like a BMP ligand by opposing Nodal and antagonizing Smad2/3 signaling, or if it works like Lefty by sequestering an essential component of the Nodal signaling pathway. In this study, we report that Panda functions as an antagonist of the TGF-β type II receptor ACVRII (Activin receptor type II), which is the only type II receptor for Nodal signaling in the sea urchin and is also a type II receptor for BMP ligands. Inhibiting translation of acvrII mRNA disrupted D/V patterning across all 3 germ layers and caused acvrII morphants to develop with a typical Nodal loss-of-function phenotype. In contrast, embryos overexpressing acvrII displayed strong ectopic Smad1/5/8 signaling at blastula stages and developed as dorsalized larvae, a phenotype very similar to that caused by over activation of BMP signaling. Remarkably, embryos co-injected with acvrII mRNA and panda mRNA did not show ectopic Smad1/5/8 signaling and developed with a largely normal dorsal-ventral polarity. Furthermore, using an axis induction assay, we found that Panda blocks the ability of ACVRII to orient the D/V axis when overexpressed locally. Using co-immunoprecipitation, we showed that Panda physically interacts with ACVRII, as well as with the Nodal co-receptor Cripto, and with TBR3 (Betaglycan), which is a non-signaling receptor for Inhibins in mammals. At the molecular level, we have traced back the antagonistic activity of Panda to the presence of a single proline residue, conserved with all the Lefty factors, in the ACVRII binding motif of Panda, instead of a serine as in most of TGF-β ligands. Conversion of this proline to a serine converted Panda from an antagonist that opposed Nodal signaling and promoted dorsalization to an agonist that promoted Nodal signaling and triggered ventralization when overexpressed. Finally, using phylogenomics, we analyzed the emergence of the agonist and antagonist form of Panda in the course of evolution. Our data are consistent with the idea that the presence of a serine at that position, like in most TGF-β, was the ancestral condition and that the initial function of Panda was possibly in promoting and not in antagonizing Nodal signaling. These results highlight the existence of key functional and structural elements conserved between Panda and Lefty, allow to draw an intriguing parallel between sea urchin Panda and mammalian Inhibin α and raise the unexpected possibility that the original function of Panda may have been in activation of the Nodal pathway rather than in its inhibition.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

IntroductionInfants born very early preterm are at high risk of language delays. However, less is known about the consequences of late prematurity. Hence, the aim of the present study is to characterize the neural encoding of speech sounds in late preterm neonates in comparison with those born at term.MethodsThe speech-evoked frequency-following response (FFR) was recorded to a consonant-vowel stimulus /da/ in 36 neonates in three different groups: 12 preterm neonates [mean gestational age (GA) 36.05 weeks], 12 “early term neonates” (mean GA 38.3 weeks), and “late term neonates” (mean GA 41.01 weeks).ResultsFrom the FFR recordings, a delayed neural response and a weaker stimulus F0 encoding in premature neonates compared to neonates born at term was observed. No differences in the response time onset nor in stimulus F0 encoding were observed between the two groups of neonates born at term. No differences between the three groups were observed in the neural encoding of the stimulus temporal fine structure.DiscussionThese results highlight alterations in the neural encoding of speech sounds related to prematurity, which were present for the stimulus F0 but not for its temporal fine structure.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

BackgroundFunctional impairment is one of the most decisive prognostic factors in patients with complex chronic diseases. A more significant functional impairment indicates that the disease is progressing, which requires implementing diagnostic and therapeutic actions that stop the exacerbation of the disease. ObjectiveThis study aimed to predict alterations in the clinical condition of patients with complex chronic diseases by predicting the Barthel Index (BI), to assess their clinical and functional status using an artificial intelligence model and data collected through an internet of things mobility device. MethodsA 2-phase pilot prospective single-center observational study was designed. During both phases, patients were recruited, and a wearable activity tracker was allocated to gather physical activity data. Patients were categorized into class A (BI≤20; total dependence), class B (2060; moderate or mild dependence, or independent). Data preprocessing and machine learning techniques were used to analyze mobility data. A decision tree was used to achieve a robust and interpretable model. To assess the quality of the predictions, several metrics including the mean absolute error, median absolute error, and root mean squared error were considered. Statistical analysis was performed using SPSS and Python for the machine learning modeling. ResultsOverall, 90 patients with complex chronic diseases were included: 50 during phase 1 (class A: n=10; class B: n=20; and class C: n=20) and 40 during phase 2 (class B: n=20 and class C: n=20). Most patients (n=85, 94%) had a caregiver. The mean value of the BI was 58.31 (SD 24.5). Concerning mobility aids, 60% (n=52) of patients required no aids, whereas the others required walkers (n=18, 20%), wheelchairs (n=15, 17%), canes (n=4, 7%), and crutches (n=1, 1%). Regarding clinical complexity, 85% (n=76) met patient with polypathology criteria with a mean of 2.7 (SD 1.25) categories, 69% (n=61) met the frailty criteria, and 21% (n=19) met the patients with complex chronic diseases criteria. The most characteristic symptoms were dyspnea (n=73, 82%), chronic pain (n=63, 70%), asthenia (n=62, 68%), and anxiety (n=41, 46%). Polypharmacy was presented in 87% (n=78) of patients. The most important variables for predicting the BI were identified as the maximum step count during evening and morning periods and the absence of a mobility device. The model exhibited consistency in the median prediction error with a median absolute error close to 5 in the training, validation, and production-like test sets. The model accuracy for identifying the BI class was 91%, 88%, and 90% in the training, validation, and test sets, respectively. ConclusionsUsing commercially available mobility recording devices makes it possible to identify different mobility patterns and relate them to functional capacity in patients with polypathology according to the BI without using clinical parameters.

Abstract Type 1 diabetes mellitus (T1D) patients face daily difficulties in keeping their blood glucose levels within appropriate ranges. Several techniques and devices, such as flash glucose meters, have been developed to help T1D patients improve their quality of life. Most recently, the data collected via these devices is being used to train advanced artificial intelligence models to characterize the evolution of the disease and support its management. Data scarcity is the main challenge for generating these models, as most works use private or artificially generated datasets. For this reason, this work presents T1DiabetesGranada, an open under specific permission longitudinal dataset that not only provides continuous glucose levels, but also patient demographic and clinical information. The dataset includes 257 780 days of measurements spanning four years from 736 T1D patients from the province of Granada, Spain. This dataset advances beyond the state of the art as one the longest and largest open datasets of continuous glucose measurements, thus boosting the development of new artificial intelligence models for glucose level characterization and prediction.

Abstract Background Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD). Methods Prospective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose. Results Of the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%. Conclusions Using a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

Abstract The insulin-degrading enzyme (IDE) is an evolutionarily conserved zinc-dependent metallopeptidase highly expressed in the brain, where its specific functions remain poorly understood. Besides insulin, IDE is able to cleave many substrates in vitro, including amyloid beta peptides, making this enzyme a candidate pathophysiological link between Alzheimer's disease (AD) and type 2 diabetes (T2D). These antecedents led us to address the impact of IDE absence in hippocampus and olfactory bulb. A specific induction of microgliosis was found in the hippocampus of IDE knockout (IDE-KO) mice, without any effects in neither hippocampal volume nor astrogliosis. Performance on hippocampal-dependent memory tests is influenced by IDE gene dose in 12-month-old mice. Furthermore, a comprehensive characterization of the impact of IDE haploinsufficiency and total deletion in metabolic, behavioral, and molecular parameters in the olfactory bulb, a site of high insulin receptor levels, reveals an unambiguous barcode for IDE-KO mice at that age. Using wildtype and IDE-KO primary microglial cultures, we performed a functional analysis at the cellular level. IDE absence alters microglial responses to environmental signals, resulting in impaired modulation of phenotypic states, with only transitory effects on amyloid-β management. Collectively, our results reveal previously unknown physiological functions for IDE in microglia that, due to cell-compartment topological reasons, cannot be explained by its enzymatic activity, but instead modulate their multidimensional response to various damaging conditions relevant to aging and AD conditions.

Recent developments in ultrashort and intense laser systems have enabled the generation of short and brilliant proton sources, which are valuable for studying plasmas under extreme conditions in high-energy-density physics. However, developing sensors for the energy selection, focusing, transport, and detection of these sources remains challenging. This work presents a novel and simple design for an isochronous magnetic selector capable of angular and energy selection of proton sources, significantly reducing temporal spread compared to the current state of the art. The isochronous selector separates the beam based on ion energy, making it a potential component in new energy spectrum sensors for ions. Analytical estimations and Monte Carlo simulations validate the proposed configuration. Due to its low temporal spread, this selector is also useful for studying extreme states of matter, such as proton stopping power in warm dense matter, where short plasma stagnation time (

Background: to prove the effectivity of fertility-sparing procedures in early-stage ovarian cancer by assessing pregnancy rates and obstetrical outcomes. Methods: we performed a retrospective multicenter study among 55 Spanish hospitals, collecting patients from 18 to 40 years old with diagnosis of early-stage ovarian cancer, epithelial (EOC) or non-epithelial (non-EOC), from January 2010 to December 2019. Data on the use of assisted reproductive techniques, pregnancy attempts and obstetrical outcomes were collected. Results: a total of 150 patients met inclusion criteria, 70 (46.6%) EOC and 80 (53.4%) non-EOC. Pregnancy attempts were reported in 51 (34%) patients, with 42 (28%) patients carrying the pregnancy to term. Among them, 30 (71.4%) underwent surgery alone and 12 (28.6%) had additional postoperative chemotherapy. A total of 32 (76.1% patients) had spontaneous pregnancies and 10 (23.9%) required in vitro fertilization. There was only one (2.4%) complication reported. Vaginal delivery was reported in twenty-nine (69%) patients and cesarean section in five (11.9%) patients. Conclusions: fertility-sparing management for ovarian cancer seems to be an option with proven good pregnancy rates and low complications. The selection of patients must consider strict criteria in order to maintain a good prognosis.

The objective of the current study was to adapt and validate the pure procrastination scale (PPS) for the Spanish adult population. Procrastination can have numerous consequences in daily life, making it essential to have reliable and valid instruments for measuring procrastination. Thus, this study was conducted to address this need. The sample consisted of 596 adults aged 18–83 years (M = 35.25, SD = 13.75). In addition to the PPS, participants completed two procrastination measures, namely the irrational procrastination scale and the decisional procrastination questionnaire, alongside the Big Five inventory and the satisfaction with life scale. The results of the confirmatory factor analysis revealed a three-factor structure of the PPS. The examination of the reliability of scores in terms of internal consistency and temporal stability showed satisfactory results for the PPS scores. Moreover, gender invariance was observed at the scalar level. Finally, the PPS scores correlated with other measures of procrastination, personality traits, and satisfaction with life in the expected direction and magnitude. In conclusion, the Spanish PPS offers valid and reliable scores when administered to adult population.

Objective: To examine the clinical effects of combining motor imagery-based neurofeedback training with bilateral repetitive transcranial magnetic stimulation for upper limb motor function in subacute and chronic stroke. Design: Clinical trial following an AB/BA crossover design with counterbalanced assignment. Subjects: Twenty individuals with subacute (n = 4) or chronic stroke (n = 16). Methods: Ten consecutive sessions of bilateral repetitive transcranial magnetic stimulation alone (therapy A) were compared vs a combination of10 consecutive sessions of bilateral repetitive transcranial magnetic stimulation with 12 non-consecutive sessions of motor imagery-based neurofeedback training (therapy B). Patients received both therapies (1-month washout period), in sequence AB or BA. Participants were assessed before and after each therapy and at 15-days follow-up, using the Fugl-Meyer Assessment-upper limb, hand-grip strength, and the Nottingham Sensory Assessment as primary outcome measures. Results: Both therapies resulted in improved functionality and sensory function. Therapy B consistently exhibited superior effects compared with therapy A, according to Fugl-Meyer Assessment and tactile and kinaesthetic sensory function across multiple time-points, irrespective of treatment sequence. No statistically significant differences between therapies were found for hand-grip strength. Conclusion: Following subacute and chronic stroke, integrating bilateral repetitive transcranial magnetic stimulation and motor imagery-based neurofeedback training has the potential to enhance functional performance compared with using bilateral repetitive transcranial magnetic stimulation alone in upper limb recovery.

Resumo Objetivo Validar a elaboração de uma escala para mensurar a carga de trabalho das parteiras com base na Classificação das Intervenções de Enfermagem (NIC) por meio da sua aplicação multicêntrica em diferentes unidades de parto. Métodos Estudo quantitativo, longitudinal, de caráter multicêntrico, realizado em três hospitais universitários gerais da rede pública de saúde. A amostra foi composta por cinquenta parteiras, que examinaram a validade de construto da escala elaborada, com um total de 370 partos. A coleta de dados iniciou-se por meio da escala elaborada ad hoc pela equipe de pesquisa, contabilizando o tempo e o número médio de intervenções NIC, realizadas a cada nascimento. Resultados As parteiras do estudo estão sujeitas a um aumento na sua carga de trabalho quanto ao número e ao tempo médio gasto na realização das NIC em cada parto atendido. Em sua jornada de trabalho (turno de 12 horas), elas destinam 960,61 minutos (16 horas no turno diurno) e 840,29 minutos (14 horas no turno noturno) para executar suas funções na assistência ao parto. Conclusões Os dados indicam a validade da escala elaborada ad hoc, pois esse instrumento reflete a real carga de trabalho vivenciada pelas parteiras do estudo.

Porous silicon carbide (SiC) ceramics with three different pore sizes (∼7, ∼45, and ∼98 μm) and three different porosities (∼40 %, ∼54 %, and ∼63 %) were prepared from mixtures of SiC, polysiloxane, boron carbide, phenolic resin, and polymer microbeads to investigate the effect of the pore size of porous SiC ceramics on their flexural strength. As the pore size increased from ∼7 to ∼98 μm, the flexural strength decreased from 116.3 to 80.8 MPa at a constant porosity of 40 %, owing to the increased defect size. The typical flexural strengths of porous SiC ceramics fabricated using ∼8 and ∼100 μm templates were 84.9 and 60.6 MPa respectively, at 54 % porosity; the flexural strengths were 58.7 and 43.9 MPa, respectively, at 63 % porosity. These results suggest that depending on the application, the mechanical properties of porous SiC ceramics can be successfully tuned by adjusting their pore size and porosity.

BackgroundThe COVID-19 pandemic has impacted the mental health of patients with substance use disorder (SUD). However, few longitudinal studies have been done which examine associations between the pandemic, SUD patients’ mental health and their drug use.ObjectivesThis study aimed to examine duration of abstinence according to psychiatric status among SUD outpatients followed-up for 18 months from the pandemic related lockdown.MethodsA follow-up study of 316 SUD outpatients was undertaken. Sociodemographic features, and clinical and consumption related variables were recorded. Pre, during and post lockdown information was evaluated. Abstinence/substance use was monitored at the patient’s scheduled follow-up appointments, and psychiatric disorders and psychological variables were revaluated at 18 months.ResultsSurvival analyses were used to compare the duration of abstinence (in months) from the beginning of the lockdown. It was observed that 70% of patients consumed the main substance for which they were being treated at some point during the follow-up. Men, younger patients, those with more symptoms of anxiety and personality disorders, and patients who experienced increased craving during follow-up, showed shorter duration of abstinence. While patients who had previously maintained at least one year of abstinence, achieved better results.ConclusionsDuring the first year and a half of the pandemic, SUD outpatients presented alterations in mental health, such us anxiety, depression and maladaptive personality traits and a high rate of relapse. For this reason, despite the health and social crisis and their restrictive measures, a comprehensive treatment should be ensured.

The COVID-19 pandemic had a detrimental effect on mental health since its start in 2020 and current data on mental health is limited. This study provides recent longitudinal data on psychological distress among a country-wide sample of adults. We recruited and surveyed 1,956 adults in Spain in April 2021 and August 2022 on sociodemographic- and pandemic-related psychological distress using the General Distress 21-item version of the Depression, Anxiety, and Stress Scale (DASS). Paired sampled t-tests assessed DASS scores by sex from April 2021 to August 2022; and one-way ANOVAs assessed DASS scores across sociodemographic characteristics. Results showed that psychological distress slightly improved across the total sample from April 2021 to August 2022; though females, young adults, students, and individuals with lower income experienced more psychological distress. Increases in severe stress scores were found particularly among men. Our data provides an overview of the psychological distress of Spanish adults 2.5 years into the pandemic and provides novel evidence that though life has resumed a sense of normalcy after the COVID-19 pandemic, the mental health of key populations (e.g., females, young adults, students, low-income) is still suffering and further intervention and resources are needed.

Introduction. Community-acquired pneumonia is a leading cause of mortality and hospital admissions. The aetiology remains unknown in 30–65% of the cases. Molecular tests are available for multiple pathogen detection and are under research to improve the causal diagnosis. Methods. We carried out a prospective study to describe the clinical characteristics and aetiology of community-acquired pneumonia during the COVID-19 pandemic and to assess the diagnostic effectivity of the microbiological tests, including a molecular test of respiratory pathogens (FilmArray™ bioMérieux). Results. From the 1st of February 2021 until the 31st of March 2022, 225 patients were included. Failure in microorganism identification occurred in approximately 70% of patients. Streptococcus pneumoniae was the most common isolate. There were 5 cases of viral pneumonia. The tested FilmArray exhibited a low positivity rate of 7% and mainly aided in the diagnosis of viral coinfections. Conclusions. Despite our extensive diagnostic protocol, there is still a low rate of microorganism identification. We have observed a reduction in influenza and other viral pneumoniae during the COVID-19 pandemic. Having a high NEWS2 score on arrival at the emergency department, an active oncohematological disease or chronic neurological conditions and a positive microbiological test result were related to worse outcomes. Further research is needed to determine the role of molecular tests in the microbiological diagnosis of pneumonia.

IntroductionLong survivors after childhood cancer are increasing thanks to oncological improvements. Their quality of life and fertility-sparing should be considered in the early phases of each oncological pathway. Cryopreservation of ovarian tissue removed before starting gonadotoxic therapies is the only fertility sparing procedure available for prepubertal children affected by cancer and it does not affect the timing of the start of the treatment.Materials and methodsThe present study shows the surgical and clinical outcomes following laparoscopic ovarian tissue collection (LOTC) for a total of 311 patients aged between 0 and 17 years old from four different European Centers.ResultsOnly two major complications were reported according to the Clavien Dindo classification (0.6%).DiscussionLOTC can be considered a safe procedure.

This study aimed to explore whether the relationship between perceptual (rating of perceived exertion; RPE) and mechanical (maximal number of repetitions completed [MNR], fastest set velocity, and mean velocity decline) variables is affected by the length of inter-set rest periods during resistance training sets not leading to failure. Twenty-three physically active individuals (15 men and eight women) randomly completed 12 testing sessions resulting from the combination of two exercises (bench press and bench pull), three inter-set rest protocols (1, 3, and 5 min), and two minimal velocity thresholds (farther from muscular failure [MVT0.45 for bench press and MVT0.65 for bench pull] and closer to muscular failure [MVT0.35 for bench press and MVT0.55 for bench pull]). The duration of inter-set rest periods did not have a significant impact on RPE values (p ranged from 0.061 to 0.951). Higher proximities to failure, indicated by lower MVTs, were associated with increased RPE values (p < 0.05 in 19 out of 24 comparisons). Moreover, as the number of sets increased, an upward trend in RPE values was observed (p < 0.05 in seven out of 12 comparisons). Finally, while acknowledging some inconsistencies, it was generally observed that higher magnitudes of the mechanical variables, especially MNR (rs < −0.55 in three out of four comparisons), were associated with lower RPE values. These results, which were comparable for the bench press and bench pull exercises, suggest that post-set RPE values are affected by the fatigue experienced at both the beginning and end of the set.

Abstract During early development of the sea urchin embryo, activation of ERK signalling in mesodermal precursors is not triggered by extracellular RTK ligands but by a cell-autonomous, RAS-independent mechanism that was not understood. We discovered that in these cells, ERK signalling is activated through the transcriptional activation of a gene encoding a protein related to Kinase Suppressor of Ras, that we named KSR3. KSR3 belongs to a family of catalytically inactive allosteric activators of RAF. Phylogenetic analysis revealed that genes encoding kinase defective KSR3 proteins are present in most non-chordate metazoa but have been lost in flies and nematodes. We show that the structure of KSR3 factors resembles that of several oncogenic human RAF mutants and that KSR3 from echinoderms, cnidarians and hemichordates activate ERK signalling independently of RAS when overexpressed in cultured cells. Finally, we used the sequence of KSR3 factors to identify activating mutations of human B-RAF. These findings reveal key functions for this family of factors as activators of RAF in RAS-independent ERK signalling in invertebrates. They have implications on the evolution of the ERK signalling pathway and suggest a mechanism for its co-option in the course of evolution.

Herbicide-resistant corn poppy (Papaver rhoeas L.) is one of the most important broadleaved weeds and the number of resistant cases is still growing. The aims of this study were to confirm the resistance of P. rhoeas from Tunisia to ALS inhibitors and auxin mimics and investigate the mechanisms of Target-Site Resistance (TSR) and Non-Target Site Resistance (NTSR) involved. Dose–response trials to determine cross-resistance patterns for ALS inhibitors and auxin mimics were conducted in a greenhouse. In this study, multiple resistance to tribenuron-methyl and dicamba but not to 2,4-D was found in P. rhoeas populations. Cross-resistance to imazamox was confirmed as well. Sequence analysis of the ALS gene detected target-site mutations in codon 197 of the ALS gene, namely, Pro197His, Pro197Thr, Pro197Leu, and Pro197Asn. In this study, the metabolism experiments with malathion (a cytochrome P450 inhibitor) showed that malathion reduced resistance to imazamox, indicating that P450 is involved in the resistance. TSR and NTSR mechanisms to ALS inhibitors likely coexist. The findings of this study revealed a significant synergistic interaction between malathion and dicamba in particular populations, suggesting that the resistance to auxin mimics can be conferred by enhanced metabolism.

The objective of this study was to evaluate the possible use of spectrophotometric assays for the measurement of trace elements, including Zinc (Zn), Copper (Cu), Magnesium (Mg), and iron (Fe) in the saliva of horses and study their possible changes in equine gastric ulcer syndrome (EGUS). EGUS is a highly prevalent disease, with a current high incidence due to the increase in intensive management conditions. There are two EGUS diseases: equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), which can appear individually or together. For this purpose, automated spectrophotometric assays for measuring these analytes in horse saliva were analytically validated. Then, these analytes were measured in the saliva of horses with only ESGD, only EGGD, both ESGD and EGGD and a group of healthy horses. The methods used to measure the analytes were precise and accurate. Horses diagnosed with EGGD presented significantly lower levels of Zn and Mg. Fe concentrations were significantly lower in the saliva of horses with ESGD and EGGD. Overall, these results indicate that there are changes in trace elements in saliva in EGUS that could reflect the physiopathological mechanisms involved in this process and open the possibility of using trace elements as biomarkers of this syndrome.

Background/Objectives: During the COVID-19 pandemic and the burden on hospital resources, the rapid categorization of high-risk COVID-19 patients became essential, and lung ultrasound (LUS) emerged as an alternative to chest computed tomography, offering speed, non-ionizing, repeatable, and bedside assessments. Various LUS score systems have been used, yet there is no consensus on an optimal severity cut-off. We assessed the performance of a 12-zone LUS score to identify adult COVID-19 patients with severe lung involvement using oxygen saturation (SpO2)/fractional inspired oxygen (FiO2) ratio as a reference standard to define the best cut-off for predicting adverse outcomes. Methods: We conducted a single-centre prospective study (August 2020–April 2021) at Hospital del Mar, Barcelona, Spain. Upon admission to the general ward or intensive care unit (ICU), clinicians performed LUS in adult patients with confirmed COVID-19 pneumonia. Severe lung involvement was defined as a SpO2/FiO2 ratio Results: 248 patients were included. The admission LUS score showed moderate performance in identifying a SpO2/FiO2 ratio Conclusions: Although the admission LUS score had limited performance in identifying severe lung involvement, a cut-off ≥17 score was associated with an increased risk of adverse outcomes. and could play a role in the rapid categorization of COVID-19 pneumonia patients, anticipating the need for advanced care.

Background: Exercise is an accepted intervention to improve the quality of life (QoL) of breast cancer patients. Exercise programs have been developed, and all have shown satisfactory results in improving the QoL. There is a lack of research comparing different prescription modalities. The aim of this study is to evaluate the effectiveness of physical exercise (in-person and home-based, compared to the exercise recommendation) on the QoL in breast cancer patients actively undergoing treatment. Methods: This is a randomized clinical trial with three groups (in-person: guided and supervised in-person exercise program; home-based exercise: guided and supervised exercise program with streaming monitoring both as a intervention groups; and recommendation: exercise recommendation as a control group). The QoL was measured using the EORTIC QLQ-C30 questionnaire. A baseline and 24-week analysis were investigated. Results: The total sample analyzed was n = 80. The QoL improved significantly at 24 weeks in the face-to-face and home-based exercise groups, but not in the control group. Exercise in all modalities improved fatigue, nausea, vomiting, appetite, and constipation. The QoL at 24 weeks depended on active chemotherapy, tumor type, and assigned exercise group (r2 = 0.503; p < 0.001). Conclusions: The QoL in breast cancer patients undergoing active treatment improved after a 24-week exercise program, especially in face-to-face and home-based exercise. Home-based exercise and streaming-based recommendation is a viable option for exercise recommendation.

We present experimental results for the controlled mitigation of the electromagnetic pulses (EMPs) produced in the interactions of a 1 PW high-power 30 fs Ti:Sa laser VEGA-3 with solid-density targets transparent to laser-forward-accelerated relativistic electrons. This study aims at the band of very high frequencies (VHFs), i.e., those in the hundreds of MHz, which comprise the fundamental cavity modes of the rectangular VEGA-3 vacuum chamber. We demonstrate mode suppression by a tailoring of the laser-produced space charge distribution.

Neointimal hyperplasia is the main cause of vascular graft failure in the medium term. Vitamin D receptor activation modulates the biology of vascular smooth muscle cells and has been reported to protect from neointimal hyperplasia following endothelial injury. However, the molecular mechanisms are poorly understood. We have now explored the impact of the selective vitamin D receptor activator, paricalcitol, on neointimal hyperplasia, following guidewire-induced endothelial cell injury in rats, and we have assessed the impact of paricalcitol or vehicle on the expression of key cell stress factors. Guidewire-induced endothelial cell injury caused neointimal hyperplasia and luminal stenosis and upregulated the expression of the growth factor growth/differentiation factor-15 (GDF-15), the cytokine receptor CD74, NFκB-inducing kinase (NIK, an upstream regulator of the proinflammatory transcription factor NFκB) and the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Immunohistochemistry confirmed the increased expression of the cellular proteins CD74 and NIK. Paricalcitol (administered in doses of 750 ng/kg of body weight, every other day) had a non-significant impact on neointimal hyperplasia and luminal stenosis. However, it significantly decreased GDF-15, CD74, NIK and MCP-1/CCL2 mRNA expression, which in paricalcitol-injured arteries remained within the levels found in control vehicle sham arteries. In conclusion, paricalcitol had a dramatic effect, suppressing the stress response to guidewire-induced endothelial cell injury, despite a limited impact on neointimal hyperplasia and luminal stenosis. This observation identifies novel molecular targets of paricalcitol in the vascular system, whose differential expression cannot be justified as a consequence of improved tissue injury.

This research aimed to study the rostral part of the head of the six-banded armadillo, applying advanced imaging techniques such as CT. Furthermore, by combining the images obtained through this technique with anatomical cross-sections, an adequate description of the structures that constitute the rostral part of the head of this species is presented. This anatomical information could provide a valuable diagnostic tool for the clinical evaluation of different disorders in the six-banded armadillo’s nasal cavity and paranasal sinuses.

Coffee fruit cascara, which is the skin and pulp of the coffee cherry, has been authorized as a novel food for commercialization in the European Union. The present research assessed the feasibility of using spray drying to produce a soluble powder called instant cascara (IC), employing sun-dried ripe coffee cherry pulp as a raw material. Although there were no significant differences (p > 0.05) in the overall antioxidant capacity between the freeze-dried and spray-dried samples, after an in vitro simulation of the digestion process, the spray-dried sample was significantly (p < 0.05) more antioxidant. Both samples reduced physiological intracellular ROS and significantly decreased (p < 0.05) the secretion of the pro-inflammatory factor NO. Alkaloids and phenolic compounds were detected in intestinal digests. In conclusion, spray drying is a good technique for producing IC as its use does not affect its properties and causes less environmental impact than freeze drying, as calculated by life cycle assessment. Sensory analysis did not show significant differences between the commercial beverage and the IC beverage in the adult population. IC at 10 mg/mL was significantly less accepted in adolescents than the commercial beverage. Future work will include the reformulation of the IC beverage at 10 mg/mL, which has antioxidant and anti-inflammatory potential, to increase its hedonic acceptance in all consumer segments.

Introduction and aims: Obesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression. Methods: Patients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered). Results: 81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1 ± 23.8 vs 84.5 ± 6.2; p = 0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4 ± 24.7 vs 106 ± 24.7; p

O artigo trata da alocação estratégica das emendas individuais ao orçamento da União e o efeito eleitoral no desempenho dos deputados federais que atuaram na 54ª legislatura. Argumenta-se que políticos já titulares de cargo eletivo que se candidatam a reeleição direcionam os recursos orçamentários da União conquistados através de emendas individuais para lograrem êxito em suas votações municipais. Nesses termos, as três hipóteses a serem testada são de que quanto maior os valores de emendas individuais aprovadas para o município, maior à votação do parlamentar; os deputados federais aprovam suas emendas em municípios com menor nível de Índice de Desenvolvimento Humano Municipal, pois o retorno eleitoral sobre os votos é maior; e os municípios em que o autor da emenda é da mesma coligação do prefeito são preferidos para o envio de recursos. As técnicas utilizadas foram: estatística descritiva, correlação linear de Pearson, regressão linear múltipla e teste qui-quadrado. Conclui-se que as emendas individuais alocadas em municípios explicam aproximadamente 22% dos votos obtidos pelos candidatos à reeleição, restando 78% da votação do parlamentar à investigação de outras variáveis que influenciem diretamente a estratégia política para o deputado obter sucesso eleitoral.

La frequenza dei saggi sulle nuove modalità di progetto, ci impone di sondare fenomenologie che, in continuità del design, aprono prospettive diverse sia da un punto di vista genericamente culturale, sia sul campo dell’arte. Eco (dal gr. ôikos) è un prefisso usato per la composizione di parole derivate dal greco o utilizzate modernamente. A seconda dei casi eco può assumere significati diversi: casa, famiglia, organismo sociale, collettivo e dinamico. Da qui l’eterogeneità che caratterizza l’ecodesign.

Alkaloids are important bioactive molecules throughout the natural world, and in many animals they serve as a source of chemical defense against predation. Dendrobatid poison frogs bioaccumulate alkaloids from their diet to make themselves toxic or unpalatable to predators. Despite the proposed roles of plasma proteins as mediators of alkaloid trafficking and bioavailability, the responsible proteins have not been identified. We use chemical approaches to show that a ~50 kDa plasma protein is the principal alkaloid-binding molecule in blood of poison frogs. Proteomic and biochemical studies establish this plasma protein to be a liver-derived alkaloid-binding globulin (ABG) that is a member of the serine-protease inhibitor (serpin) family. In addition to alkaloid-binding activity, ABG sequesters and regulates the bioavailability of ‘free’ plasma alkaloids in vitro. Unexpectedly, ABG is not related to saxiphilin, albumin, or other known vitamin carriers, but instead exhibits sequence and structural homology to mammalian hormone carriers and amphibian biliverdin-binding proteins. ABG represents a new small molecule binding functionality in serpin proteins, a novel mechanism of plasma alkaloid transport in poison frogs, and more broadly points toward serpins acting as tunable scaffolds for small molecule binding and transport across different organisms.

Background: The work on the ESGB guidelines for diagnosis and treatment of biofilm infections began in 2012 and the result was published in 2014. The guidelines have been and still are frequently cited in the literature proving its usefulness for people working with biofilm infections. At the ESGB Biofilm conference in Mallorca 2022 (Eurobiofilms2022) the board of the ESGB decided to evaluate the 2014-guidelines and relevant publications since 2014 based on a lecture given at the Eurobiofilms2022. Guideline methods: The Delphi method for working on production of guidelines and the current ESCMID rules for guidelines are presented. The criteria for evaluation of relevant literature are very strict and especially for treatment, most clinicians and regulatory authorities require convincing results from Level I (randomized controlled trials) publications to justify changes of treatments. The relevant new biofilm literature and the relevant biofilm presentations from the Eurobiofilms meetings and ECCMID conferences was used for evaluating the contemporary relevance of the ESGB 2014 guidelines. Diagnosis of biofilm infections: Several infectious diseases have been recognized as biofilm infections since 2014, but the diagnostic methods and therapeutic strategies are still the same as recommended in the 2014 ESGB guidelines which are summarized in this opinion paper. Treatment of biofilm infections: Some promising new in vitro and in vivo (animal experiments) observations and reports for therapy of biofilm infections are mentioned, but they still await clinical trials. Conclusion: The interim opinion at the present time (2022) is therefore, that the guidelines do not need revision now, but there is a need for survey articles discussing new methods of diagnosis and treatment of biofilm infections in order - hopefully – to give inspiration to conduct clinical trials which may lead to progress in diagnosis and treatment of patients with biofilm infections.

Introdução: O Programa de Gerenciamento de Antimicrobianos (PGA) requer a aplicação de instrumental que favoreça agilidade, acurácia e confiabilidade do registro dos dados, dado a alto volume de informações envolvido com esses pacientes. Objetivo: Implantar uma ferramenta de registro eletrônico para o acompanhamento farmacoterapêutico eletrônico de antimicrobianos em um Hospital Universitário de referência no Nordeste do Brasil. Métodos: Entre 2019 a 2022 a ferramenta foi desenvolvida com as seguintes etapas: 1) reuniões técnicas entre o time PGA, Serviço de Controle de Infecção Hospitalar e Área da Tecnologia da Informação para melhor entendimento do fluxo; 2) alinhamento dos processos de trabalho; 3) avaliação das necessidades e parâmetros a serem contemplados; 4) fase inicial de teste do protótipo do modelo; 5) treinamento dos envolvidos na tríade prescrição-emissão do parecer-dispensação e 6) divulgação e implementação do novo formato nas diversas Unidades de Internação do Hospital. Este estudo submetido ao Comitê de Ética com número de aprovação 3697674. Resultados: Após implantação foram analisadas 5.970 fichas do PGA. O instrumento de gerenciamento de ATM eletrônico foi setorizado em quatro macro seções. Estas, foram divididas quanto aos parâmetros que avaliam os dados sociodemográficos do paciente, os clínico-terapêuticos, os microbiológicos e as intervenções do PGA/intervenções farmacêuticas. Na sessão referente aos dados sociodemográficos tem-se 10 parâmetros como o nome completo do paciente, data de nascimento, idade e prontuário. Já nas variáveis clínicas foram contempladas 13 informações, como pode-se destacar o provável diagnóstico, os antimicrobianos em uso, com sua posologia e data de início do tratamento, além da indicação do ATM. Em relação à aba eletrônica dos dados microbiológicos resultaram em campos para culturas prévias, o microrganismo isolado e o seu antibiograma. Finalmente, na etapa final das intervenções, tem-se informações como o parecer do time operacional do PGA, bem como o desfecho de cada situação clínica pelo farmacêutico clínico. Conclusão: Portanto, entende-se que a ferramenta eletrônica de monitorização de ATM sistematizou o processo de documentação e registro. A informatização e a automação atuam como suporte estratégico para o Programa de Gerenciamento dos Antimicrobianos, otimizando os processos, armazenamento de maneira segura as informações e favorecendo o cuidado interdisciplinar.