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Adenomyosis is a commonly encountered pathology in women of reproductive age and frequently coexists with infertility. The effect of adenomyosis on fertility, particularly on in vitro fertilisation and intracytoplasmic sperm injection outcomes, is not well understood. Various pretreatment modalities have been used to improve pregnancy rates and live birth outcomes; however, because of a lack of high-quality evidence, there is no clear consensus on the best pretreatment option. This review was conducted through a PubMed search aiming to highlight the relationship between pretreatment and fertility in women with adenomyosis. Medical, ablative surgical, and non-surgical therapies were reviewed. According to the current literature, gonadotropin-releasing hormone agonist therapy and placement of a levonorgestrel intrauterine system are two suitable medical pretreatment strategies that can improve the clinical pregnancy rates of patients with adenomyosis. Surgical ablation of adenomyosis can also be beneficial, although surgical management can be challenging. Non-surgical thermal techniques, including high-intensity focused ultrasound ablation, percutaneous microwave ablation, and radiofrequency ablation, are much less invasive techniques that have shown effectiveness in improving fertility. Although evidence remains limited, all these procedures have demonstrated a favourable safety profile. Further studies are needed to better develop these techniques and demonstrate their effectiveness.

BackgroundSmall-for-gestational-age (SGA) fetuses are at increased risk of mortality and morbidity, and less than 30% will be detected by any ultrasound scan within 4 weeks before delivery. Our aim was to evaluate the relationship between neutrophil/lymphocyte ratio (NLR) in the first trimester of pregnancy and SGA fetuses.MethodWe performed a prospective study between June 2021 and August 2022, to evaluate the relationship between the neutrophil to lymphocyte ratio in maternal blood in the first trimester of pregnancy, with the birth of an SGA fetus. One hundred ninety-four participants with singleton pregnancies between 11 + 1 and 13 + 6 weeks of gestation were recruited. Pregnancies affected with diagnosed fetal chromosomal abnormalities, or chronic pathologies were excluded. SGA was defined as birthweight less than the 10th centile (N = 42) and severe SGA as birthweight less than the 3rd centile for gestation (N = 10) according to a locally derived descriptive charts. The NLR value measured in the first trimester was compared between these two groups and controls.ResultsWe found no statistically significant difference in NLR, (3.5 +/−1.2 vs. 3.4+/−1.2, p-value of 0.78) when comparing the SGA less than the 10th centile group to the control group. NLR was also not different between severe SGA and controls (3.6+/−1.4 vs. 3.4+/−1.2 p-value of 0.78).ConclusionWe found no association between first-trimester NLR ratio and SGA.

Abstract Background the problem in early diagnosis of sporadic cancer is understanding the individual’s risk to develop disease. In response to this need, global scientific research is focusing on developing predictive models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation. Methods a well-established procedure to identify proliferating circulating tumor cells was deployed to measure the cell proliferation of circulating non-haematological cells which may suggest tumor pathology. Moreover, the data collected were processed by a supervised machine learning model to make the prediction. Results the developed test combining circulating non-haematological cell proliferation data and artificial intelligence shows 98.8% of accuracy, 100% sensitivity, and 95% specificity. Conclusion this proof of concept study demonstrates that integration of innovative non invasive methods and predictive-models can be decisive in assessing the health status of an individual, and achieve cutting-edge results in cancer prevention and management.

Extracorporeal Membrane Oxygenation (ECMO) is a medical device used to support patients with severe cardiac and/or respiratory failure. It is being used more frequently to offer percutaneous mechanical circulatory support, even though the intricate interactions between ECMO and the failing heart, as well as its impact on hemodynamics and perfusion, are not yet fully understood. Within the two main types of ECMO support (the veno-venous ECMO (VV-ECMO), which is used to support only the lungs) and the veno-arterial ECMO (VA-ECMO), which is used to support the lungs and heart), consideration is given solely to the second approach. Indeed, this study focuses on the impact of different ECMO cannulation site and blood perfusion conditions on the aortic hemodynamics and organ perfusion in VA-ECMO. Using computed tomography (CT) images, we reconstructed specific aortic models based on clinical cannula configurations and placements. A detailed cannula-aorta integration model was developed to simulate the VA-ECMO blood supply environment. Employing computational fluid dynamics (CFD), we analyzed how varying ECMO perfusion levels and ECMO cannulation sites affect flow characteristics. This study provides insights into optimizing ECMO therapy by understanding its effects on blood flow and potential damage to blood and organs.

The growing recognition of the public health impact of cognitive impairment and dementia has sparked a global initiative to identify risk factors and develop strategies to prevent or slow the progression of these cognitive disorders. Uric acid, the end product of the metabolism of purine nucleotides, has been reported as a key factor of many conditions potentially involved in cognitive dysfunction/dementia. In addition, some studies support the hypothesis that elevated uric acid levels could reduce the risk of Alzheimer’s disease, slow down the decline of cognition, and delay the progression of Alzheimer’s disease, while other evidence achieves opposite positions. These discrepancies might reflect a biological ambivalence for uric acid depending on a very complex interplay of factors that include its concentrations achieved in biological fluids, the nature, and concentration of free radicals, the presence and concentration of other antioxidant molecules, potentially responsible for bi-directional effects of uric acid on brain health/functioning. In this narrative review, we attempt to elucidate the influential role of uric acid metabolism in cognitive functioning by discussing pathophysiological mechanisms putatively involved, being well aware that none of them can be considered one-sided due to the complexity of the human organism.

Purpose: In recent years, the Electroencephalography (EEG)-based Brain-Computer Interface (BCI) appli-cation has been growing rapidly and has emerged as a technology with high translational potential since it allows disabled people to translate human intentions into control signals and to interact with the external environment without any kinesthetic movement. Individuals with significant health problems can benefit from this technology to improve their independence and facilitate participation in activities, thus improving general well-being and preventing impairments. The rapid advances in technology have led to optimal innovation in the context of wearable health monitoring and remote control solutions. Many wearable devices for capturing EEG signals in daily life have recently been released on the market. Our paper aims to present a wearable de-vice-based system for real-time and remote EEG monitoring, to describe the proposed system modules and the signal processing algorithms, to explore the functionalities of this wearable EEG solution, and to suggest its potential application for daily brain data recordings in the home en-vironment. Materials and Methods: The validity of the Emotiv Epoc+ device in the continuous and real-time EEG signals acquisition and monitoring was demonstrated by means of preliminary test measurements during a resting state paradigm performed by a healthy control subject. Results: Our findings confirmed the Epoc+ reliability for event-related brain potential research and in measuring acceptable spectral EEG data. Conclusion: The described approach, focusing on the emerging area of remote monitoring sensors and wearable device applications, might be leveraged to measure complex health outcomes in non-specialist and remote settings.

Purpose: In this paper, we propose a secure wearable and portable device aiming to (i) monitor physical activity in medical and clinical rehabilitation, (ii) evaluate the subject's movements in sports environments, and (iii) monitor wellness indicators. Materials and Methods: The innovative low-power custom circuit can acquire, pre-process, digitalize, and transmit EMG signals to a Raspberry PI4 device via a low-energy Bluetooth module. The Raspberry PI4 is a hub that sends data to a cloud-based system for remote monitoring and processing. The best cybersecurity practices have been implemented: firewall, anti-DDoS and SELinux. Results: We have assessed the system's vulnerability before and after the system's hardening. SELinux makes the system safer and prevents unauthorized access to patients' data health by tampering with the devices. Conclusion: Adopting IoT systems in telemedicine requires greater attention to cybersecurity. It is necessary to implement security mechanisms to guarantee the privacy of patient's health data.

This study provides an in-depth analysis of the intersection between artificial intelligence (AI) and fashion, focusing on the potentials and ethical challenges related to the intensive use of large datasets. Using methodologies such as “Envisioning” and the “Scenario Planning Model”, the aim is to develop clear and structured approaches to the deployment of AI in the fashion industry, exploring how this technology can transform and enrich the creative process, extending human capabilities. Among the main ethical challenges are training on culturally connoted data, which risks introducing formative bias, and the need to explain AI processes and decisions in understandable terms (explainability). The possible formalization of AI methods to make their processes and results formal is also discussed. The potential capabilities of these technologies to overcome the limits of human intellect are also considered. The conclusions highlight the importance of a balance between technological innovation and ethical considerations to promote ongoing dialogue among diverse stakeholders, ensuring that AI in the fashion industry evolves inclusively, ethically, and responsibly, fostering a future where technology and human creativity coexist harmoniously.

This paper seeks to explore the interesting connection between medieval art and contemporary art, particularly in painting. The different characteristics of medieval art are also millenary instances that will see syn-thesis in the painting of Antonello da Messina. With him, a new era opens up. It will last until the threshold of the contemporary. However, from the work of Henri Rousseau onwards up to Wharol (with his pop icons) and Anish Kapoor (for his obsessive search for the purity of colour) we will see how certain artistic codes of mediaeval art are recovered and return to in-spire many contemporary artists who, in a secular key, return, consciously or unconsciously, to draw on that infinite reservoir of suggestions, and even religious images, called mediaeval art.

Este trabajo analiza los instrumentos que daban comienzo y forma inicial al proceso de representación política de una ciudad del Virreinato del Perú: los poderes y las instrucciones que el cabildo de Buenos Aires extendió a sus procuradores y agentes de negocios cortesanos entre 1580 y 1635. Se trata de unos elementos fundamentales de la comunicación a distancia, que habilitaban y configuraban parcialmente una instancia de representación cuya finalidad era manifestar y defender los intereses de la corporación ante la Corona y el Consejo de Indias. Estos instrumentos fungían como una condición necesaria para la interacción presencial entre la ciudad y la alta administración indiana de la monarquía, aunque la complejidad y la incertidumbre de las negociaciones cortesanas daban lugar a una relación imprevisible entre los mandatos capitulares, las gestiones de los agentes y su resultado normativo.

In the global context, advancements in technology and science have rendered virtual, augmented, and mixed-reality technologies capable of transforming clinical care and medical environments by offering enhanced features and improved healthcare services. This paper aims to present a mixed reality-based system to control a robotic wheelchair for people with limited mobility. The test group comprised 11 healthy subjects (six male, five female, mean age 35.2 ± 11.7 years). A novel platform that integrates a smart wheelchair and an eye-tracking-enabled head-mounted display was proposed to reduce the cognitive requirements needed for wheelchair movement and control. The approach’s effectiveness was demonstrated by evaluating our system in realistic scenarios. The demonstration of the proposed AR head-mounted display user interface for controlling a smart wheelchair and the results provided in this paper could highlight the potential of the HoloLens 2-based innovative solutions and bring focus to emerging research topics, such as remote control, cognitive rehabilitation, the implementation of patient autonomy with severe disabilities, and telemedicine.

The aim of the present study was to test a new oral contrast medium composed of natural components for the magnetic resonance (MR) imaging of small bowel diseases. Between January 2018 and June 2019, 35 patients affected by ileocolic Crohn’s disease (CD) were enrolled in the present study. Each patient underwent two sequential MR enterographies, first with the standard polyethylene glycol (PEG) water solution and, after 3 weeks, with the new natural beverage designed by our team. At the end of the administration of each oral contrast, a satisfaction survey was given to the patients to assess the palatability of both beverages. The intestinal distention and the quality of images were evaluated by two expert radiologists for both studies and the interreader agreement was calculated. According to the satisfaction questionnaire, 97.1% of patients expressed positive judgments regarding the natural beverage (71.4% very good and 25.7% good) whereas only 8.6% of them appreciated the PEG water solution (8.6% good) (p = 0.0001). The degree of intestinal distention was excellent and good in 97.1% of patients after the administration of PEG and in 94.3% of the patients after the administration of the natural beverage, without significant differences between the two products and with almost perfect (k = 0.821) and substantial (k = 0.754) inter-observer variability, respectively. No statistical differences were observed between the two expert radiologists regarding the evaluation of the imaging quality; in particular, they were considered good and excellent in 100% of patients after the administration of PEG water solution and in 97.2% of those who took the natural beverage, with substantial (k = 0.618) and almost perfect (k = 0.858) inter-observer variability, respectively. The new natural beverage demonstrated the same intestinal distension and excellent image quality compared to the synthetic standard oral contrast administered during MRE for small bowel diseases, proving to be a valid alternative with better palatability.

The synthesis of nanometer‐thick (≈3 nm) gallium oxynitride (GaOxNy) layers with a variable stoichiometry is reported. The approach primarily exploits the liquid metal chemistry (LMC) technique and promises easier integration of 2D materials onto photonic devices compared to traditional top‐down and bottom‐up methods. The fabrication follows a two‐step process, involving first liquid metal‐based printing of a nanometer‐thick layer of gallium oxide (Ga2O3), followed a plasma‐enhanced nitridation reaction. Control over nitridation parameters (plasma power, exposure time) allows adjustment of the GaOxNy layer's composition, granting access to compounds with distinct optical properties (e.g., a 20% index variation), as demonstrated by ellipsometry and density functional theory (DFT) simulations. DFT provides a microscopic understanding of the effect of the bond polarization and crystallinity on the optical properties of GaOxNy compounds. These findings expand the knowledge of ultrathin GaOxNy alloys, which are poorly studied with respect to their gallium nitride (GaN) and Ga2O3 counterparts. They also represent an essential step toward integrating such 2D materials into photonic chips and offer new opportunities to improve the performance of hybrid optoelectronic devices.

Background Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional‐based Italian cohort. Methods and Results Among 14 189 subjects aged 18 to 95 years followed‐up for 11.2 (5.3–13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high‐density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid‐lowering drugs. During 139 375 person‐years of follow‐up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8–103.3, sensitivity 76.6, specificity 34.1, P

Introduction There is growing interest in head-to-head comparison between different lipid-lowering nutraceuticals. The aim of our study was to test the lipid-lowering effect of dietary supplementation with low-dose monacolins from red yeast rice (2.8 mg per daily dose) combined with berberine (Armolipid Plus®) or highly standardized artichoke extract versus placebo. Material and methods 60 overall healthy adult volunteers with polygenic hypercholesterolemia (baseline low-density lipoprotein cholesterol (LDL-C) = 160.2 ±9.2 mg/dl) were enrolled in a 3-arm, double-blind, non-inferiority, randomized, parallel-group clinical trial. After 4-week diet standardization, enrolled individuals were randomized to be treated for 8 weeks with red yeast rice and highly standardized artichoke extracts (ATC group), Armolipid Plus®, or placebo. Results At the enrolment visit, LDL-C values were similar in the compared groups. After 8 weeks, all actively treated subjects experienced significant improvements in baseline total cholesterol (TC), LDL-C and apolipoprotein B (Apo-B) (all p < 0.01) (ATC group: TC = –18.9%, LDL-C = –26.7% (placebo-corrected: –12.4%), Apo-B = –19.6%; Armolipid Plus®: TC = –18.4%, LDL-C = –25.8% (placebo-corrected: –12.1%), Apo-B = –23.2%; placebo: TC = –6.2%, LDL-C = –8%, Apo-B = –8.4%). Participants in the ATC group attained significantly lower body mass index (BMI) values (–2.1%), while individuals treated with Armolipid Plus® showed improvements in baseline high-density lipoprotein cholesterol (HDL-C) (+8.7%) and triglyceride (TG) (+17.5%) levels. Finally, baseline hepatic steatosis index (HSI) values significantly decreased in both actively treated groups (by –2.4% and –2.4% in ATC and in Armolipid Plus®, respectively). Conclusions Patients with polygenic hypercholesterolemia experienced a significant improvement in several cardiovascular risk factors in both ATC and Armolipid Plus® groups.

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting.

Introduction In addition to healthy lifestyle and balanced diet, nutraceutical supplementation may be useful to maintain overall metabolic wellness. The aim of the present study was to assess the metabolic and vascular effects of a new, highly standardized bergamot phytocomplex supplement in healthy volunteers with the features of metabolic syndrome. Material and methods We carried out a double-blind, randomized, placebo-controlled, three-arm, parallel-group clinical trial in 90 adult subjects (30 per group) treated for 12 weeks with two different dosages of a highly standardized bergamot phytocomplex (Endoberg by AKHYNEX and Kalita by Giellepi) or placebo. Lipid plasma levels, glycemia, plasma hs-CRP, HOMA-IR, body fat, endothelial reactivity and fatty liver index were assessed at baseline, after 6 weeks and at the end of treatment in all subjects. Results At the end of treatment, both tested bergamot extract doses were able to significantly improve atherogenic dyslipidemia and insulin sensitivity (p < 0.05) compared to placebo. In the high-dose treated group, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) improved versus placebo (p < 0.05) just after 6 weeks of treatment. After 12 weeks of treatment, TC decreased by 13.2 ±2.1%, LDL-C by 17.7 ±3.2%, non-HDL-C by 17.5 ±3.1%, TG by 16.6 ±3.3%, TG/HDL-C by 22.5 ±4.4%, homeostasis insulin resistance index (HOMA-IR) by 12.2 ±2.1%, -glutamyl transferase (GGT) by 22.2 ±4.6%, and high-sensitivity C-reactive protein (hs-CRP) by 17.9 ±3.4% versus baseline (p < 0.05) and vs. placebo (p < 0.05). Percentage body fat and endothelial reactivity improved versus baseline, but not versus placebo, in the high-dose treatment only (p < 0.05). Conclusions The tested bergamot phytocomplex was able to significantly improve glucose and lipid metabolism, as well as inflammation, and might represent a novel multi-target approach to control metabolic syndrome.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07–6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

Implementation of marker-assisted selection (MAS) in modern beekeeping would improve sustainability, especially in breeding programs aiming for resilience against the parasitic mite Varroa destructor. Selecting honey bee colonies for natural resistance traits, such as brood-intrinsic suppression of varroa mite reproduction, reduces the use of chemical acaricides while respecting local adaptation. In 2019, eight genomic variants associated with varroa non-reproduction in drone brood were discovered in a single colony from the Amsterdam Water Dune population in the Netherlands. Recently, a new study tested the applicability of these eight genetic variants for the same phenotype on a population-wide scale in Flanders, Belgium. As the properties of some variants varied between the two studies, one hypothesized that the difference in genetic ancestry of the sampled colonies may underly these contribution shifts. In order to frame this, we determined the allele frequencies of the eight genetic variants in more than 360 Apis mellifera colonies across the European continent and found that variant type allele frequencies of these variants are primarily related to the A. mellifera subspecies or phylogenetic honey bee lineage. Our results confirm that population-specific genetic markers should always be evaluated in a new population prior to using them in MAS programs.

Injuries represent a serious concern for football players, with a significant loss in terms of sport participation and long periods of rehabilitation. According to the 2019/20 UEFA Élite Club Injury Report, the average incidence of injuries during training is 2.8 per 1000 h of training, with an average absence from training of 20 days. In addition, injured athletes are 4 to 7 times more likely to relapse than uninjured athletes. High workloads and reduced recovery periods represent two of the most important modifiable risk factors. In this context, prevention and an adequate rehabilitation protocol are vital in managing injuries, reducing their incidence, and improving the return to competition. In recent years, technological development has provided new tools in rehabilitation, and Virtual reality (VR) has shown interesting results in treating neurologic and orthopedic pathologies. Virtual Reality (VR) technology finds application in the sports industry as a tool to examine athletes’ technical movements. The primary objective is to detect the biomechanical risk factors associated with anterior cruciate ligament injury. Additionally, VR can be used to train athletes in field-specific techniques and create safe and controlled therapeutic environments for post-injury recovery. Moreover, VR offers a customizable approach to treatment based on individual player data. It can be employed for both prevention and rehabilitation, tailoring the rehabilitation and training protocols according to the athletes’ specific needs.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04–1.27], p < 0.001 and HR 1.25 [1.09–1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based molecules have emerged as interesting materials for optoelectronic applications due to the possibility to easily fine-tune their photophysical and optical properties, dominated by two main absorption bands in the visible range. However, no studies have been reported on the nature of these spectral features. By means of ultrafast spectroscopy, we detect intramolecular energy transfer in a spin-coated film of di-thieno-phenyl BODIPY (DTPBDP) dispersed in a polystyrene matrix after pumping the high-energy absorption band. The same effect is not present upon pumping the lowest-energy band, which instead allows the achievement of efficient amplified spontaneous emission. Density functional calculations indicate the different nature of the two main absorption bands, explaining their different photophysical behavior.

Bile acids (BAs) and bilirubin, primarily known for their role in lipid metabolism and as heme catabolite, respectively, have been found to have diverse effects on various physiological processes, including oxidative stress and inflammation. Indeed, accumulating evidence showed that the interplay between BAs and bilirubin in these processes involves intricate regulatory mechanisms mediated by specific receptors and signaling pathways under certain conditions and in specific contexts. Oxidative stress plays a significant role in the development and progression of cardiovascular diseases (CVDs) due to its role in inflammation, endothelial dysfunction, hypertension, and other risk factors. In the cardiovascular (CV) system, recent studies have suggested that BAs and bilirubin have some opposite effects related to oxidative and inflammatory mechanisms, but this area of research is still under investigation. This review aims to introduce BAs and bilirubin from a biochemical and physiological point of view, emphasizing their potential protective or detrimental effects on CVDs. Moreover, clinical studies that have assessed the association between BAs/bilirubin and CVD were examined in depth to better interpret the possible link between them.

This article presents a comprehensive investigation into the functionalization of methoxyphenylazobenzene using electron-directing groups located at the meta position relative to the azo group. Spectroscopic analysis of meta-functionalized azobenzenes reveals that the incorporation of electron-withdrawing units significantly influences the absorption spectra of both E and Z isomers, while electron-donating functionalities lead to more subtle changes. The thermal relaxation process from Z to E result in almost twice as prolonged for electron-withdrawing functionalized azobenzenes compared to their electron-rich counterparts. Computational analysis contributes a theoretical understanding of the electronic structure and properties of meta-substituted azobenzenes. This combined approach, integrating experimental and computational techniques, yields significant insights into the structure–property relationship of meta-substituted asymmetrical phenolazobenzenes.

Abstract When viruses like SARS-CoV-2 infect cells, they reprogram the repertoire of cellular and viral transcripts that are being translated to optimize their strategy of replication, often targeting host translation initiation factors, particularly eIF4F complex consisting of eIF4E, eIF4G and eIF4A. A proteomic analysis of SARS-CoV-2/human proteins interaction revealed viral Nsp2 and initiation factor eIF4E2, but a role of Nsp2 in regulating translation is still controversial. HEK293T cells stably expressing Nsp2 were tested for protein synthesis rates of synthetic and endogenous mRNAs known to be translated via cap- or IRES-dependent mechanism under normal and hypoxic conditions. Both cap- and IRES-dependent translation were increased in Nsp2-expressing cells under normal and hypoxic conditions, especially mRNAs that require high levels of eIF4F. This could be exploited by the virus to maintain high translation rates of both viral and cellular proteins, particularly in hypoxic conditions as may arise in SARS-CoV-2 patients with poor lung functioning.

Abstract Background MEN1, which codes for the protein menin, is a tumor suppressor in neuroendocrine tissue. In cholangiocarcinoma (CCA) cell lines the overexpression of menin decreased proliferation, angiogenesis, migration, and invasion in vitro and in xenografts, but its expression in CCA tumor tissue samples is not established. Objective Determine whether the expression of menin correlates with disease progression in patient samples of CCA in a tissue microarray (TMA) by immunohistochemical (IHC) staining. Results IHC analysis of 97 biopsies revealed that low-grade tumors (Grade I) exhibited intense, diffuse, finely granular nuclear menin immunoreactivity with a pronounced linear perinuclear pattern (mean IHC score = 2.00), whereas high-grade tumors (Grade III) mostly lacked such staining (mean IHC score = 0.35). Collectively, there was a significant inverse association between tumor grade and menin staining (P = 0.0005). We also found a significant association between fibrosis status and menin staining, in that, 81.2% (56/69) of patients without fibrosis had no menin staining, whereas 92.9% (26/28) patients with fibrosis exhibited menin staining (P

Bioactive peptides (BPs) are a heterogeneous class of molecules found in a wide range of plant and animal sources. BPs have a number of different industrial applications including pharmacology (nutraceuticals), food, cosmetology, and pet food. Though BPs were initially used mainly as food additives, today the estimated peptide-based product market is around US $40 billion per year, highlighting consumer demand. The nutraceutical field is one of the most interesting applications for BPs, however there are some limitations to the efficacy of BPs in nutraceutical treatments, including low bioaccessibility and bioavailability. Thus, new extraction and isolation techniques have been developed, using both vegetable and animal sources, to obtain BPs with specific activities and improve the bioactivity and the bioavailability. Randomized clinical trials show a possible relationship between the administration of BPs and the reduction of several cardiovascular risk factors, including hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycaemia. In addition, BPs exhibit antioxidant, anti-inflammatory, antimicrobial, and anticancer potential, but long-term clinical studies are still needed. The aim of this review is to give a general introduction of BPs, describe their production and application methods, present data regarding bioactivity and bioavailability, and finally highlight the future prospects of this class of molecules in clinical practice.

Tunable plasmonic materials capable of surviving harsh environments are critical for advanced applications. Here, the authors report that some high-entropy transition-metal carbides can satisfy the requirements.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan–Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Honey bee colonies have great societal and economic importance. The main challenge that beekeepers face is keeping bee colonies healthy under ever-changing environmental conditions. In the past two decades, beekeepers that manage colonies of Western honey bees (Apis mellifera) have become increasingly concerned by the presence of parasites and pathogens affecting the bees, the reduction in pollen and nectar availability, and the colonies’ exposure to pesticides, among others. Hence, beekeepers need to know the health condition of their colonies and how to keep them alive and thriving, which creates a need for a new holistic data collection method to harmonize the flow of information from various sources that can be linked at the colony level for different health determinants, such as bee colony, environmental, socioeconomic, and genetic statuses. For this purpose, we have developed and implemented the B-GOOD (Giving Beekeeping Guidance by computational-assisted Decision Making) project as a case study to categorize the colony’s health condition and find a Health Status Index (HSI). Using a 3-tier setup guided by work plans and standardized protocols, we have collected data from inside the colonies (amount of brood, disease load, honey harvest, etc.) and from their environment (floral resource availability). Most of the project’s data was automatically collected by the BEEP Base Sensor System. This continuous stream of data served as the basis to determine and validate an algorithm to calculate the HSI using machine learning. In this article, we share our insights on this holistic methodology and also highlight the importance of using a standardized data language to increase the compatibility between different current and future studies. We argue that the combined management of big data will be an essential building block in the development of targeted guidance for beekeepers and for the future of sustainable beekeeping.

Introduction Bergamot and opuntia (prickly pear cladodes) standardized extracts have been demonstrated to have positive metabolic effects in preclinical and clinical models. Material and methods The aim of this study was to evaluate the metabolic effect of a combined nutraceutical containing 150 mg of Opuntia ficus Indica extract, 400 mg of plant sterols, 12.5 mg of thiamine, and 200 mg of Brumex® a phytocomplex from bergamot fruit (Citrus bergamia Risso et Poiteau, fructus) standardized 40% in total flavonoids and min 5% in 3-hydroxy-3-methylglutaryl-flavanones. Thus, we carried out a randomized, double-blind, placebo-controlled clinical trial on 75 hypercholesterolaemic subjects randomized to take the active compound (2 tablets per day), placebo (2 tablets per day), or both (1 per product per day). Results After 12 weeks of treatment with 1 tablet per day, we observed a significant reduction of a number of metabolic parameters: total cholesterol (TC) (–14.6%), low-density lipoprotein cholesterol (LDL-C) (–19.9%), non-high-density lipoprotein cholesterol (non-HDLC) (–22.1%), triglycerides (TG) (–13.1%), Apolipoprotein B (–16%) (all p < 0.05 both versus baseline and versus placebo), fasting plasma glucose (–5.1%), glutamate oxaloacetate transaminase (–7.8%), glutamate pyruvate transaminase (–7.3%), and -glutamyl transferase (–34.4%) (all p < 0.05 versus baseline). High-density lipoprotein cholesterol (HDL-C) was increased 6.9% by the use of 1 tablet per day (p < 0.05 versus baseline). All parameters were reduced to the same extent when taking the full dose (2 tablets), beyond TG. Conclusions The tested nutraceutical compound based on a flavonoid complex from bergamot and opuntia showed a short-term positive impact on plasma lipids, fasting plasma glucose, and liver enzyme in overall healthy subjects affected by hypercholesterolaemia with low cardiovascular risk.

Este artículo aborda el problema de la comunicación política mantenida por las ciudades de la provincia del Paraguay y Río de la Plata a través del estudio de la procuraduría cortesana de Manuel de Frías. La representación que este agente realizó en Madrid de los intereses de las ciudades que conformaban dicha jurisdicción se extendió entre los años 1614 y 1618. Se trató de una estancia prolongada que tuvo un fuerte impacto en la producción legislativa real para el área. Su incidencia se manifestó en el ritmo del despacho de cédulas reales, en los asuntos regulados por ellas, e, incluso, en su formulación textual. La investigación busca restituir el calado de la participación de los súbditos en la definición de las normas sancionadas en Madrid por el rey que regulaban algunos aspectos centrales para la región. Además, analiza varios asuntos relevantes del proceso comunicacional, como la conformación, no exenta de contradicciones, de una instancia de representación de carácter provincial, y la función de la información de la gobernación que circulaba hacia la corte para apoyar los intereses de los espacios locales y convertirse en insumos legislativos esenciales.

Metastases account for the majority of prostate cancer (PCa) deaths, and targeting them is a major goal of systemic therapy. We identified a novel interaction between two kinases: tousled‐like kinase 1 (TLK1) and MAP kinase‐activated protein kinase 5 (MK5) that promotes PCa spread. In PCa progression, TLK1–MK5 signalling appears to increase following antiandrogen treatment and in metastatic castration‐resistant prostate cancer (mCRPC) patients. Determinations of motility rates (2D and 3D) of different TLK1‐ and MK5‐perturbed cells, including knockout (KO) and knockdown (KD), as well as the use of specific inhibitors, showed the importance of these two proteins for in vitro dissemination. We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells. Expression of MK5‐S354A or kinase‐dead MK5 in MK5‐depleted mouse embryonic fibroblast (MEF) cells failed to restore their motility compared with that of wild‐type (WT) MK5‐rescued MK5−/− MEF cells. A pMK5‐S354 antiserum was used to establish this site as an authentic TLK1 target in androgen‐sensitive human prostate adenocarcinoma (LNCaP) cells, and was used in immunohistochemistry (IHC) studies of age‐related PCa sections from TRAMP (transgenic adenocarcinoma of the mouse prostate) mice and to probe a human tissue microarray (TMA), which revealed pMK5‐S354 level is correlated with disease progression (Gleason score and nodal metastases). In addition, The Cancer Genome Atlas (TCGA) analyses of PCa expression and genome‐wide association study (GWAS) relations identify TLK1 and MK5 as potential drivers of advanced PCa and as markers of mCRPC. Our work suggests that TLK1–MK5 signalling is functionally involved in driving PCa cell motility and clinical features of aggressiveness; hence, disruption of this axis may inhibit the metastatic spread of PCa.