Brain clocks capture diversity and disparity in aging and dementia.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R²=0.37, F²=0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.

Beware with the backpack! New hosts and pathogens identified for Ixodes simplex ticks collected from bats in the Iberian Peninsula.

To improve the knowledge on the role of bats in the maintenance and transmission of tick-borne pathogens, a molecular approach was used to characterize Anaplasma spp., Rickettsia spp., Coxiella burnetii, Borrelia burgdorferi s.l., piroplasmids, Hepatozoon spp., flaviviruses and nairoviruses in ticks collected from Iberian bats. A total of 732 bats from 25 species were captured at 38 sampling sites distributed in seven provinces of Spain between 2018 and 2022. Seventy-nine Ixodes simplex ticks were collected from 31 bats (Eptesicus isabellinus, Hypsugo savii, Myotis capaccini, Myotis emarginatus, Myotis myotis, Miniopterus schreibersii, Pipistrellus pipistrellus and Rhinolophus ferrumequinum). Sixty of 79 I. simplex were positive for at least one pathogen tested and were collected from 23 bats captured in southeast Spain. We detected the presence of Rickettsia slovaca in 12 ticks collected from M. emarginatus, H. savii, M. schreibersii and E. isabellinus; Rickettsia aeschlimannii in 1 tick from M. schreibersii; Anaplasma ovis in 3 ticks from H. savii and M. schreibersii; C. burnetii in 2 ticks from H. savii; Occidentia massiliensis in 1 tick from H. savii; piroplasmids in 12 ticks from H. savii, M. schreibersii and E. isabellinus; and a novel nairovirus in 1 tick from M. schreibersii. Furthermore, blood samples obtained from 14 of the 31 tick-infested bats were negative in all PCR analyses. This study describes new host and pathogen associations for the bat-specialist I. simplex, highlights the risk of spread of these pathogens, and encourages further research to understand the role of Iberian bats in the epidemiology of tick-borne pathogens.

Design of Wearable Textile Electrodes for the Monitorization of Patients with Heart Failure.

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

Multi-organ clinical ultrasound as a complement to the diagnostic process in an internal medicine consultation.

INTRODUCTION: Evaluating outpatient cases in internal medicine consultations presents a significant diagnostic challenge. Ultrasound can be a highly useful tool in assessment and decision-making. PATIENTS AND METHODS: A prospective observational study was conducted on a cohort of patients attending an internal medicine rapid assessment clinic. Eighty patients were prospectively recruited. A medical consultation was conducted as per usual clinical practice, followed by a POCUS evaluation; collecting pulmonary, cardiac, and abdominal data. All findings were analyzed and recorded, particularly those that were significant or altered the initial diagnosis, subsequent tests, or treatment. RESULTS: Significant ultrasound findings were found in 37.5% of the patients. Of all ultrasound scans, the most clinically relevant were in the heart region (31.9%), followed by the abdomen (26%). These findings led to a change in overall management in 27.5% of patients. Using logistic regression, a model was developed to estimate the presence of clinically relevant findings with an area under the curve (AUC) of 0.78 (95% CI 0.66-0.89; p < 0.001) with 80% Sensitivity and 66% Specificity. CONCLUSION: The systematic and standardized incorporation of clinical ultrasound in internal medicine consultations contributes to decision-making, can provide significant findings that allow for modifications in clinical suspicion and therapeutic management.

Cross-cultural comparison of the performance on the Five-Point test between highly educated comparable samples of Argentina and South Africa.

OBJECTIVE: The study aimed to carry out a cross-cultural analysis by comparing Five-Point test scores for two different countries. The Five-Point test measures design fluency, an executive function, and is an inexpensive test that makes it more accessible to assessment settings, including under-resourced settings. METHODS: Adults in Argentina (n = 90) and South Africa (n = 90) with tertiary levels of education were tested on the Five-Point Test. ANOVA was applied to compare the scores of the two groups on the total number of unique designs produced (Total Unique Designs). RESULTS: The study found no significant differences in the Total Unique Designs scores between the two groups (p = .13; η = 0.01). Correlations between demographic variables and the Total Unique Designs scores varied slightly across both samples. CONCLUSIONS: Despite large cultural differences between both samples (language, race, religion, income) scores on this test did not differ significantly. These findings provide initial evidence of scalar equivalence on the test across these samples. Norms for the Five-Point Test Total Unique Designs scores might be used interchangeably between these two highly educated groups from different countries.

Diagnosis and treatment of myocarditis and inflammatory cardiomyopathy. Consensus document of the SEC-Working Group on Myocarditis.

Myocarditis is defined as myocardial inflammation and its etiology is highly diverse, including infectious agents, drugs, and autoimmune diseases. The clinical presentation also varies widely, extending beyond the classic clinical picture of acute chest pain, and includes cases of cardiomyopathy of unknown cause whose etiology may be inflammatory. Because certain patients may benefit from targeted treatments, the search for the etiology should begin when myocarditis is first suspected. There remain several areas of uncertainty in the diagnosis and treatment of this disease. Consequently, this consensus document aims to provide clear recommendations for its diagnosis and treatment. Hence, a diagnostic algorithm is proposed, specifying when non-invasive diagnosis with cardiac MR is appropriate vs a noninvasive approach with endomyocardial biopsy. In addition, more novel aspects are discussed, such as when to suspect an underlying genetic etiology. The recommendations cover the management of myocarditis and inflammatory cardiomyopathy, both for general complications and specific clinical entities.

Patients' Opinions on Antibiotics in the Treatment of Dental Infections: A Cross-Sectional Survey.

Background: The aim of this study was to evaluate patients' knowledge and perceptions of the use of systemic antibiotics in the treatment of endodontic infections and to determine the possible contribution of patients to the development of bacterial resistance. Methods: A total of 550 patients were asked to respond to a survey on the perception of systemic antibiotic use in the treatment of endodontic infections and antibiotic resistance during January 2022 and March 2023. A bivariate and multivariate analysis was performed to determine possible correlates in the population regarding antibiotic use in the endodontic world. Results: A total of 514 patients were included in the study, 65.9% of whom were women. While 34.6% of the population studied thought that it was always necessary to take antibiotics prior to endodontics, 49.4% considered that they were necessary after endodontics, regardless of the clinical symptoms. The prevalence of self-medication was 17.3%, and women self-medicate more than men, with significant differences (p < 0.05), although they have a greater knowledge of antibiotic resistance than men (p < 0.05). Forty-four percent of the population expected to take antibiotics when faced with dental pain, mainly women (p < 0.05). Conclusions: The general population is contributing to the serious problem of bacterial resistance. It is necessary to promote educational strategies focused on the correct use of antibiotics in the community. The worst results were found mainly in the population with a low level of education. The level of education was the variable that most influenced the knowledge and attitudes of the population, followed by the sex of the participants.

Crimean-Congo haemorrhagic fever virus in questing non-Hyalomma spp. ticks in Northwest Spain, 2021.

Crimean-Congo haemorrhagic fever (CCHF) unexpectedly emerged in humans in Northwest Spain in 2021, and two additional cases were reported in the region in 2022. The 2021 case was associated with a tick bite on the outskirts of the city where the patient lived. PCR analysis of 95 questing ticks collected in the outskirts of that city in 2021, none of the genus Hyalomma, revealed a prevalence of confirmed CCHF virus (CCHFV) infection of 10.5%. Our results in this emerging scenario suggest the need to consider that CCHFV may be effectively spreading to Northwest Spain and to urgently understand any possible role of non-Hyalomma spp. ticks in the eco-epidemiological dynamics of CCHFV.

TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus.

Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-É£ (IFN-É£) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-É£ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-É£ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-É£ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-É£ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.

Assessing the complementary information from an increased number of biologically relevant features in liquid biopsy-derived RNA-Seq data.

Liquid biopsy-derived RNA sequencing (lbRNA-seq) exhibits significant promise for clinic-oriented cancer diagnostics due to its non-invasiveness and ease of repeatability. Despite substantial advancements, obstacles like technical artefacts and process standardisation impede seamless clinical integration. Alongside addressing technical aspects such as normalising fluctuating low-input material and establishing a standardised clinical workflow, the lack of result validation using independent datasets remains a critical factor contributing to the often low reproducibility of liquid biopsy-detected biomarkers. Considering the outlined drawbacks, our objective was to establish a workflow/methodology characterised by: 1. Harness the rich diversity of biological features accessible through lbRNA-seq data, encompassing a holistic range of molecular and functional attributes. These components are seamlessly integrated via a Machine Learning-based Ensemble Classification framework, enabling a unified and comprehensive analysis of the intricate information encoded within the data. 2. Implementing and rigorously benchmarking intra-sample normalisation methods to heighten their relevance within clinical settings. 3. Thoroughly assessing its efficacy across independent test sets to ascertain its robustness and potential utility. Using ten datasets from several studies comprising three different sources of biological material, we first show that while the best-performing normalisation methods depend strongly on the dataset and coupled Machine Learning method, the rather simple Counts Per Million method is generally very robust, showing comparable performance to cross-sample methods. Subsequently, we demonstrate that the innovative biofeature types introduced in this study, such as the Fraction of Canonical Transcript, harbour complementary information. Consequently, their inclusion consistently enhances prediction power compared to models relying solely on gene expression-based biofeatures. Finally, we demonstrate that the workflow is robust on completely independent datasets, generally from different labs and/or different protocols. Taken together, the workflow presented here outperforms generally employed methods in prediction accuracy and may hold potential for clinical diagnostics application due to its specific design.

Introducing Photo-Cross-Linkable Functionalities on P(VDF-co-TrFE) Ferroelectric Copolymer.

Ferroelectric polymers have emerged as crucial materials for the development of advanced organic electronic devices. Their recent high-end commercial applications as fingerprint sensors have only increased the amount of scientific interest around them. Despite an ever-larger body of studies focusing on optimizing the properties of ferroelectric polymers by physical means (e. g., annealing, stretching, blending or nano-structuring), post-polymerization chemical modification of such polymers has only recently become a field of active study with great promise in expanding the scope of those polymers. In this work, a solution-based post-polymerization modification method was developed for the safe and facile grafting of a plethora of functional groups to the backbone of commercially available Poly(vinylidene fluoride-co-trifluoroethylene P(VDF-co-TrFE) ferroelectric polymers. To showcase the versatility of this approach, photosensitive groups were grafted onto the polymeric backbone, enabling them to undergo photo-cross-linking. Finally, these modified polymers were used as functional negative photoresists in a photolithographic process, highlighting the potential of this method to integrate ferroelectric fluorinated electroactive polymers into standard electronic microfabrication production lines.

HBsAg level defines different clinical phenotypes of HBeAg(-) chronic HBV infection related to HBV polymerase-specific CD8+ cell response quality.

Background: HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8+ T-cell response. Aims: To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8+ T-cell response. Methods: We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8+ cell effector function were correlated with HBsAg level. Results: A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8+ T-cell proliferation against at least two HBV epitopes was higher in HBsAg < 1,000 IU/ml group. CD8+ T-cell expansion after HBVpolymerase456-63-specific stimulation was impaired in HBsAg > 1,000 IU/ml group, while the response against HBVcore18-27 was preserved and response against envelope183-91 was nearly abolished, regardless of HBsAg level. Cases with preserved HBVpolymerase456-63 CD8+ cell response had lower LS/duration of infection and APRI/duration of infection rates. HBV-polymerase456-63-specific CD8+ T-cell proliferation intensity was negatively correlated with LS/years of infection ratio. Conclusion: HBsAg > 1,000 IU/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8+ T-cell response.

Identifying key environmental factors to model Alt a 1 airborne allergen presence and variation.

Fungal spores, commonly found in the atmosphere, can trigger important respiratory disorders. The glycoprotein Alt a 1 is the major allergen present in conidia of the genus Alternaria and has a high clinical relevance for people sensitized to fungi. Exposure to this allergen has been traditionally assessed by aerobiological spore counts, although this does not always offer an accurate estimate of airborne allergen load. This study aims to pinpoint the key factors that explain the presence and variation of Alt a 1 concentration in the atmosphere in order to establish exposure risk periods and improve forecasting models. Alternaria spores were sampled using a Hirst-type volumetric sampler over a five-year period. The allergenic fraction from the bioaerosol was collected using a low-volume cyclone sampler and Alt a 1 quantified by Enzyme-Linked ImmunoSorbent Assay. A cluster analysis was executed in order to group days with similar environmental features and then analyze days with the presence of the allergen in each of them. Subsequently, a quadratic discriminant analysis was performed to evaluate if the selected variables can predict days with high Alt a 1 load. The results indicate that higher temperatures and absolute humidity favor the presence of Alt a 1 in the atmosphere, while time of precipitation is related to days without allergen. Moreover, using the selected parameters, the quadratic discriminant analysis to predict days with allergen showed an accuracy rate between 67 % and 85 %. The mismatch between daily airborne concentration of Alternaria spores and allergen load can be explained by the greater contribution of medium-to-long distance transport of the allergen from the major emission sources as compared with spores. Results highlight the importance of conducting aeroallergen quantification studies together with spore counts to improve the forecasting models of allergy risk, especially for fungal spores.

Pulmonary thrombosis associated with COVID-19 pneumonia: Beyond classical pulmonary thromboembolism.

BACKGROUND: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. METHODS: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. RESULTS: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. CONCLUSIONS: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".

How to handle off-label prescriptions of rupatadine, a second-generation antihistamine and PAF antagonist: a review.

The off-label use of second-generation antihistamines, used outside of the formal indications authorized by regulatory authorities, in different age groups, doses or in special populations, is very common for many allergic, autoimmune and dermatological diseases. The off-label use of rupatadine (a second-generation antihistamine with PAF antagonist activity) in these conditions is reviewed here, including in combination with immunotherapy in the treatment of food allergy or allergic rhinitis, at high doses in chronic urticaria, and with prescriptions of less common but challenging conditions such as skin pruritus or mast cell activation disorders like mastocytosis. Rupatadine use is reviewed herein to confirm if its off-label management is supported by well-designed clinical trials or by published real-world cases. This review will contribute to increasing compliance and achieving better results in clinical practice. Off-label use of rupatadine should be left to the discretion of the prescribing healthcare professional after careful clinical evaluation.

Beyond the Meso/Macroporous Boundary: Extending Capillary Condensation-Based Pore Size Characterization in Thin Films Through Tailored Adsorptives.

The characterization of thin films containing nanopores with diameters exceeding 50 nm poses significant challenges, especially when deploying sorption-based techniques. Conventional volumetric physisorption or mercury intrusion methods have limited applicability in thin films due to constraints in sample preparation and nondestructive testing. In this context, ellipsometric porosimetry represents a viable alternative, leveraging its optical sensitivity to thin films. With existing setups relying on the capillary condensation of volatile compounds such as water, applicability is typically restricted to pore dimensions <50 nm. In this study, we introduce two high-molar-mass hydrocarbon adsorptives, namely ethylbenzene and n-nonane. These adsorptives exhibit substantial potential in improving the accuracy of physisorption measurements beyond mesoporosity (i.e., >50 nm). Specifically, with n-nonane, applicability is extended up to 80 nm pores. Our measurement guidelines propose a nondestructive, expeditious (<60 min), low-pressure (<0.03 bar) approach to investigate nanoporous thin films with potential adaptability to diverse structural architectures.

Gender differences in clinical features and outcomes of patients over 75 years presenting with acute heart failure. Results of a nationwide study (2016-2019).

BACKGROUND: Heart failure (HF) is a major health problem in Western countries, and a leading cause of hospitalizations and death. There is a scarcity of data on the influence of sex on HF outcomes in elderly patients. The aim of the present study was to analyze differences between men and women in clinical characteristics, in-hospital mortality, 30-day HF readmission rates, cardiovascular mortality and HF readmission rates at 1 year after discharge in patients older than 75 years hospitalized for HF in Spain. METHODS: Retrospective analysis of patients discharged with a main diagnosis of HF from all Spanish public hospitals between 2016 and 2019. Patients aged 75 years or older were selected, and a comparison was made between male and female patients. RESULTS: From 2016 to 2019, a total of 354,786 episodes of HF in this age subgroup were identified, 59.2% being women. The overall mean age was 85.2 ± 5.4 years, being higher in women (85.9 ± 5.5 vs. 84.2 ± 5.3 years, p < 0.001). Risk-adjusted in-hospital mortality was lower in women (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.92-0.97; p < 0.001). Female sex also showed a protective effect for 30-day readmissions, with an OR of 1.06 (95% CI: 1.04-1.09; p < 0.001). One-year cardiovascular mortality (24.1% vs. 25.0%; p < 0.001) and one-year HF readmission rates (30.8% vs. 31.6%; p = 0.001) were lower in women. CONCLUSIONS: Almost 60% of hospital admissions for HF in people aged 75 years or older between 2016 and 2019 in Spain were female patients. Female sex seems to play a protective role on in-hospital mortality and the rate of admissions and mortality at 1 year after discharge.

Materials Science Toolkit for Carbon Footprint Assessment: A Case Study for Endoscopic Accessories of Common Use.

Ironically, healthcare systems are key agents in respiratory-related diseases and estimated deaths because of the high impact of their greenhouse gas emissions, along with industry, transportation, and housing. Based on safety requirements, hospitals and related services use an extensive number of consumables, most of which end up incinerated at the end of their life cycle. A thorough assessment of the carbon footprint of such devices typically requires knowing precise information about the manufacturing process, which is rarely available in detail because of the many materials, pieces, and steps involved during the fabrication. Yet, the tools most often used for determining the environmental impact of consumer goods require a bunch of parameters, mainly based on the material composition of the device. Here, we report a basic set of analytical methods that provide the information required by the software OpenLCA to calculate the main outcome related to environmental impact, greenhouse gas emissions. Through thermogravimetry, calorimetry, infrared spectroscopy, and elemental analysis, we proved that obtaining relevant data for the calculator in the exemplifying case of endoscopy tooling or accessories is possible. This routine procedure opens the door to a broader, more accurate analysis of the environmental impact of everyday work at hospital services, offering potential alternatives to minimize it.

A comprehensive review of unmanned aerial vehicle-based approaches to support photovoltaic plant diagnosis.

Accurate photovoltaic (PV) diagnosis is of paramount importance for reducing investment risk and increasing the bankability of the PV technology. The application of fault diagnostic solutions and troubleshooting on operating PV power plants is vital for ensuring optimal energy harvesting, increased power generation production and optimised field operation and maintenance (O&M) activities. This study aims to give an overview of the existing approaches for PV plant diagnosis, focusing on unmanned aerial vehicle (UAV)-based approaches, that can support PV plant diagnostics using imaging techniques and data-driven analytics. This review paper initially outlines the different degradation mechanisms, failure modes and patterns that PV systems are subjected and then reports the main diagnostic techniques. Furthermore, the essential equipment and sensor's requirements for diagnosing failures in monitored PV systems using UAV-based approaches are provided. Moreover, the study summarizes the operating conditions and the various failure types that can be detected by such diagnostic approaches. Finally, it provides recommendations and insights on how to develop a fully functional UAV-based diagnostic tool, capable of detecting and classifying accurately failure modes in PV systems, while also locating the exact position of faulty modules.